Introduction: Transitioning to more efficacious Antiretrovirals for HIV infected pregnant women and infant prophylaxis has reduced Mother to child transmission of HIV significantly. This study aimed to determine HIV i...Introduction: Transitioning to more efficacious Antiretrovirals for HIV infected pregnant women and infant prophylaxis has reduced Mother to child transmission of HIV significantly. This study aimed to determine HIV infection status in HIVexposed infants who had their first DNA polymerase chain reaction test in our molecular Laboratory. Subjects, Materials and Methods: Dried Blood Spots for HIV DNA results from 5 states between 2009 and 2020 were analyzed in the PCR laboratory of the Federal Teaching Hospital, Gombe. Results: Nine thousand eight hundred and twenty-three Human Immunodeficiency Virus Deoxyribonucleic acid polymerase Chain Reaction results were analysed;4937 (50.2%) were males. During the study period, there was an overall declining trend in the mother-to-child transmission rate from 3.8% in 2009 to 1.0% in 2020. 6120 (62.3%) of HIV + mothers received Highly active antiretroviral therapy HAART before pregnancy. 7845 (76.2%) of the infants received Nevirapine prophylaxis. Dried blood spot samples were collected from 4077 (41.5%) at 6 - 8 weeks. 8438 (85.9%) received cotrimoxazole. 9469 (96.4%) were ever breastfed. Of the 9823 HIV DNA PCR results, 255 (2.6%) were positive while 69/4077 (1.7%) and 109/2662 (4.1%) were positive for HIV DNA at 6 - 8 weeks and > 12 weeks respectively. (p = 0.001). 86/747 (11.5%) of infants whose HIV-positive mothers received no ARVS were HIV DNA positive. (p = 0.001). 106/884 (12.0%) of infants who had no Antiretroviral prophylaxis had positive HIV DNA results;7/413 (1.7%) with Zidovudine/Nevirapine prophylaxis had positive results. (p = 0.001). 246/9469 (2.6%) of infants that were ever breastfed were positive for HIV DNA;11/354 (3.0%) that never breastfed had positive HIV DNA. Conclusion: Lack of maternal/infant ARVs and prolonged breastfeeding increased the risk of infant HIV infection.展开更多
BACKGROUND Gastric cancer(GC) ranks as the third leading cause of cancer-related death worldwide. Epigenetic alterations contribute to tumor heterogeneity in early stages.AIM To identify the specific deoxyribonucleic ...BACKGROUND Gastric cancer(GC) ranks as the third leading cause of cancer-related death worldwide. Epigenetic alterations contribute to tumor heterogeneity in early stages.AIM To identify the specific deoxyribonucleic acid(DNA) methylation sites that influence the prognosis of GC patients and explore the prognostic value of a model based on subtypes of DNA methylation.METHODS Patients were randomly classified into training and test sets. Prognostic DNA methylation sites were identified by integrating DNA methylation profiles and clinical data from The Cancer Genome Atlas GC cohort. In the training set, unsupervised consensus clustering was performed to identify distinct subgroups based on methylation status. A risk score model was built based on Kaplan-Meier, least absolute shrinkage and selector operation, and multivariate Cox regression analyses. A test set was used to validate this model.RESULTS Three subgroups based on DNA methylation profiles in the training set were identified using 1061 methylation sites that were significantly associated with survival. These methylation subtypes reflected differences in T, N, and M category, age, stage, and prognosis. Forty-one methylation sites were screened as specific hyper-or hypomethylation sites for each specific subgroup. Enrichment analysis revealed that they were mainly involved in pathways related to carcinogenesis, tumor growth, and progression. Finally, two methylation sites were chosen to generate a prognostic model. The high-risk group showed a markedly poor prognosis compared to the low-risk group in both the training [hazard ratio(HR) = 2.24, 95% confidence interval(CI): 1.28-3.92, P < 0.001] and test(HR = 2.12, 95%CI: 1.19-3.78, P = 0.002) datasets.CONCLUSION DNA methylation-based classification reflects the epigenetic heterogeneity of GC and may contribute to predicting prognosis and offer novel insights for individualized treatment of patients with GC.展开更多
A retrospective study of flow cytometric measurements on paraffin-embedded tumor specimens from 188 patients with bladder tumor was conducted. The results were analyzed in combination with the morphological variation ...A retrospective study of flow cytometric measurements on paraffin-embedded tumor specimens from 188 patients with bladder tumor was conducted. The results were analyzed in combination with the morphological variation of bladder tumors. It was found that the DNA ploid pottern, degree of infiltration and the multiplicity of bladder tumor were closely related with tumor recurrence, among which the DNA ploid pattern was most significant. In aneuploid bladder tumors the recurrent rate and mean annual recurrence frequency were 76.7% and 1.46, and those in the diploid bladder tumors were 18.7% and 0.33 respectively. Aneuploid was the most indicative parameter of the recurrence in bladder tumors. In addition, according to the DNA ploid pattern and DNA index (DI), the aneuploid tumors in our group were divided into 4 types, namely, tetraploid tumors, npn-euploid with DI(?)1.5, non-euploid tumors with DI>1.5 and two-aneuploid tumors. The results showed that the recurrent rate of tetraploid tumors was relatively lower and it became higher and higher in the following order: non-euploid tumors with DI(?)1.5, non-euploid tumors with DI>1.5, and two-aneuploid tumors. This indicates that there are different biological behaviors in tumors with different ploid pattern. Finally, the correlation between DNA ploid pattern and tumor metastasis was also discussed.展开更多
Gallium nitride- (GaN) based high electron mobility transistors (HEMTs) provide a good platform for biological detection. In this work, both Au-gated AlInN/GaN HEMT and AlGaN/GaN HEMT biosensors are fabricated for...Gallium nitride- (GaN) based high electron mobility transistors (HEMTs) provide a good platform for biological detection. In this work, both Au-gated AlInN/GaN HEMT and AlGaN/GaN HEMT biosensors are fabricated for the detection of deoxyribonucleic acid (DNA) hybridization. The Au-gated AIInN/GaN HEMT biosensor exhibits higher sensitivity in comparison with the AlGaN/GaN HEMT biosensor. For the former, the drain-source current (VDS = 0.5 V) shows a clear decrease of 69μA upon the introduction of 1μmolL^-1 (μM) complimentary DNA to the probe DNA at the sensor area, while for the latter it is only 38 μA. This current reduction is a notable indication of the hybridization. The high sensitivity can be attributed to the thinner barrier of the AlInN/GaN heterostructure, which makes the two-dimensional electron gas channel more susceptible to a slight change of the surface charge.展开更多
Touch deoxyribonucleic acid(DNA)refers to the DNA that is left behind from skin cells when a person touches or comes into contact with an object.In crimes where the identification of suspects becomes a challenge,touch...Touch deoxyribonucleic acid(DNA)refers to the DNA that is left behind from skin cells when a person touches or comes into contact with an object.In crimes where the identification of suspects becomes a challenge,touch DNA has been a proven investigative tool.The present study aims to provide a systematic review of the role of touch DNAin criminal cases which discusses the nature and importance of touch DNA evidence at crime scenes;various phenomena including the transfer and persistence of touched samples;different factors affecting the touch sample deposition and DNA shedding;the best recovery methods and collection of samples from different substrates;and the interpretation of profiles through advanced techniques that identify the suspects.The present study also aims to optimize standard protocols in the laboratories for touched samples appropriate to the substrates that improve the success rate of profiles from touched items.展开更多
Deoxyribonucleic acid(DNA)genetic markers and ribonucleic acid(RNA)molecular markers have been widely used in forensic practices including individual identification,parentage testing,body fluid identification,determin...Deoxyribonucleic acid(DNA)genetic markers and ribonucleic acid(RNA)molecular markers have been widely used in forensic practices including individual identification,parentage testing,body fluid identification,determination of the age of stains,and molecular pathological diagnosis.Variant information of biological evidence and their interrelation could be revealed by the integrated detection of DNA/RNA markers.The integrated detection workflow aims to simplify working procedures,reduce time consuming and save valuable samples collected from crime scenes.Next-generation sequencing(NGS)may be an effective method for integrated DNA/RNA detection.In this review,DNA/RNA co-extraction strategies,simultaneous detection methods based on capillary electrophoresis were summarized.Research on NGS-based integrated detection methods of DNA and RNA markers was reviewed to provide a reference for forensic medicine researches and applications.展开更多
Aims: The purpose of this study was to determine the sex of primary and permanent tooth pulp tissue under different environmental conditions using deoxyribonucleic acid (DNA) analysis and the polymerase chain reaction...Aims: The purpose of this study was to determine the sex of primary and permanent tooth pulp tissue under different environmental conditions using deoxyribonucleic acid (DNA) analysis and the polymerase chain reaction (PCR) amplification method. Materials and Methods: For this study, 40 permanent and primary teeth (20 males and 20 females) that were scheduled for extraction were used. For 6 months, the teeth were divided into four groups of ten (5 males and 5 females) based on different environmental conditions. The pulp was extracted from each tooth, DNA was isolated using QIAGEN’s DNeasy Blood and Tissue Kit, and sex was determined using a PCR technique. Results: DNA was extracted from all 40 samples subjected to various environmental conditions, but sex was correctly determined in only 90% of the samples. Conclusions: PCR-based sex determination using primary and permanent teeth under different environmental conditions for up to 6 months is a reliable technique with high accuracy.展开更多
DNA-linked 2D and 3D nano-assemblies find use in a diverse set of applications, ranging from DNA-origami in drug delivery and medical imaging, to DNA-linked nanoparticle structures for use in plasmonics and (bio)sen...DNA-linked 2D and 3D nano-assemblies find use in a diverse set of applications, ranging from DNA-origami in drug delivery and medical imaging, to DNA-linked nanoparticle structures for use in plasmonics and (bio)sensing. However, once these structures have been fully assembled, few options are available to modulate structure geometry. Here, we investigated the use of the polycation spermine to induce DNA collapse in small oligonucleotide-linked (54 bp) gold nanoparticle structures by monitoring shifts in the localized surface plasmon resonance (LSPR) peak and by comparing the data with finite-difference time-domain (FDTD) simulations. Our data shows that low concentrations of spermine can be applied to induce large changes in DNA conformation, leading to a significant reduction in interparticle distance (from - 25 to - 3 nm) and enhanced plasmonic coupling. The DNA collapse is near-instantaneous and reversible, and its application at low and high DNA densities is demonstrated with surface plasmon resonance imaging (SPRi), showing the potential of spermine to dynamically modulate distances and geometry in DNA-based nano-assemblies.展开更多
The exploitation of electrocatalysts with high activity and durability for HER is desirable for future energy systems,but it is still a challenge.NMPs have attracted increasing attentions,but the preparation process o...The exploitation of electrocatalysts with high activity and durability for HER is desirable for future energy systems,but it is still a challenge.NMPs have attracted increasing attentions,but the preparation process often needs toxic regents or dangerous reaction conditions.Herein,we develop a general green method to fabricate metal-rich NMPs anchored on NPG through pyrolyzing DNA cross-linked complexes.The obtained Ru_(2) P-NPG exhibits an ultrasmall overpotential of 7 mV at 10 mA cm^(2) and ultralow Tafel slope of 33 mV dec^(-1) in 1.0 mol L?1 KOH,even better than that of commercial Pt/C.In addition,Ru 2 P-NPG also shows low overpotentials of 29 and 78 mV in 0.5 mol L^(-1) H_(2)SO_(4) and 1.0 mol L^(-1) PBS,respectively.The superior activity can be attributed to the ultrafine dispersion of Ru 2 P nanoparticles for more accessible sites,more defects formed for abundant active sites,the two-dimensional plane structure for accelerated electron transfer and mass transport,as well as the regulation of electron distribution of the catalyst.Moreover,the synthetic method can also be applied to prepare other metal-rich noble metal phosphides(Pd_(3)P-NPG and Rh_(2)P-NPG),which also exhibits high activity for HER.This work provides an effective strategy for designing NMP-based electrocatalysts.展开更多
Metastatic castrate-resistant prostate cancer remains a disease hard to cure,and for this reason predictive tools to monitor disease progression and therapy response are an urgent need.In this respect,liquid biopsy on...Metastatic castrate-resistant prostate cancer remains a disease hard to cure,and for this reason predictive tools to monitor disease progression and therapy response are an urgent need.In this respect,liquid biopsy on circulating cell-free nucleic acids represents an interesting strategy based on robust data.The low invasiveness and the possibility to target circulating cell-free tumor deoxyribonucleic acid underline the high specificity,sensitivity and clinical usability of the technique.Moreover,it has been observed that the cell-free tumor deoxyribonucleic acid of metastatic castrate-resistant prostate cancer patients can be representative of the tumor heterogeneity.Cell-free tumor deoxyribonucleic acids express the same behaviors as mutations:Variation in gene copy number or the methylation rate of the tumor tissue.Recently,circulating cell-free ribonucleic acid molecules have emerged as interesting markers to stratify the disease.Due to high-throughput technologies,liquid biopsy on circulating cell-free nucleic acids will soon be utilized in the clinical management of metastatic castrate-resistant prostate cancer patients.展开更多
Interactions between deoxyribonucleic acid(DNA) and metal ions are vital for maintaining life functions, however,there are still unsolved questions about its mechanisms. It is of great practical significance to study ...Interactions between deoxyribonucleic acid(DNA) and metal ions are vital for maintaining life functions, however,there are still unsolved questions about its mechanisms. It is of great practical significance to study these issues for medical chip design, drug development, health care, etc. In this investigation, the conductivity properties of λ-DNA solutions with mono-/divalent metal ions(Na+, K^(+), Mg^(2+), and Ca^(2+)) are experimentally studied as they are electrically driven through a 5 μm microfluidic channel. Experimental data indicate that the conductivities of λ-DNA solutions with metal ions(M+/M2+) basically tend to reduce firstly and then increase as the voltage increases, of which the turning points varied with the metal ions. When the voltage surpasses turning points, the conductivity of λ-DNA-M+solutions increases with the concentration of metal ions, while that of λ-DNA-M^(2+)solutions decrease. Moreover, the conductivity of λ-DNA-M^(2+)solutions is always smaller than that of λ-DNA-M+solutions, and with high-concentration M^(2+), it is even smaller than that of the λ-DNA solution. The main reasons for the above findings could be attributed to the polarization of electrodes and different mechanisms of interactions between metal ions and λ-DNA molecules. This investigation is helpful for the precise manipulation of single DNA molecules in micro-/nanofluidic space and the design of new biomedical micro-/nanofluidic sensors.展开更多
BACKGROUND Efficient extraction of nucleic acids and proteins(ENAP)from cells is a prerequisite for precise annotation of gene function,and has become laboratory routine for revealing the mysteries of life.However,cel...BACKGROUND Efficient extraction of nucleic acids and proteins(ENAP)from cells is a prerequisite for precise annotation of gene function,and has become laboratory routine for revealing the mysteries of life.However,cell samples are often from different culture dishes,resulting in inevitable experimental errors and sometimes poor repeatability.AIM To explore a method to improve the efficiency of ENAP,minimizing errors in ENAP processes,enhancing the reliability and repeatability of subsequent experimental results.METHODS A protocol for the sequential isolation of RNA,DNA,and proteins from the same cultured HepG2 cells using RNAzol reagent is presented here.The first step involves culturing HepG2 cells to the exponential phase,followed by the sequential isolation of RNA,DNA,and proteins from the same cultured cells in the second step.The yield of nucleic acids and proteins is detected in the third step,and their purity and integrity are verified in the last step.RESULTS The procedure takes as few as 3-4 d from the start to quality verification and is highly efficient.In contrast to the existing kits and reagents,which are primarily based on independent isolation,this RNAzol reagent-based method is characterized by the sequential isolation of RNA,DNA,and proteins from the same cells,and therefore saves time,and has low cost and high efficiency.CONCLUSION The RNA,DNA,and proteins isolated using this method can be used for reverse transcription-polymerase chain reaction,polymerase chain reaction,and western blotting,respectively.展开更多
The treatment and prognosis of malignant tumors are closely related to the time when the tumors are diagnosed;the earlier the diagnosis of the tumor,the better the prognosis.However,most tumors are not detected in the...The treatment and prognosis of malignant tumors are closely related to the time when the tumors are diagnosed;the earlier the diagnosis of the tumor,the better the prognosis.However,most tumors are not detected in the early stages of screening and diagnosis.It is of great clinical significance to study the correlation between multiple pathogeneses of tumors and explore simple,safe,specific,and sensitive molecular indicators for early screening,diagnosis,and prognosis.The Septin 9(SEPT9)gene has been found to be associated with a variety of human diseases,and it plays a role in the development of tumors.SEPT9 is a member of the conserved family of cytoskeletal GTPase,which consists of a P-loop-based GTP-binding domain flanked by a variable N-terminal region and a C-terminal region.SEPT9 is involved in many biological processes such as cytokinesis,polarization,vesicle trafficking,membrane reconstruction,deoxyribonucleic acid repair,cell migration,and apoptosis.Several studies have shown that SEPT9 may serve as a marker for early screening,diagnosis,and prognosis of some malignant tumors,and have the potential to become a new target for anti-cancer therapy.This article reviews the progress in research on the SEPT9 gene in early screening,diagnosis,and prognosis of tumors.展开更多
The progress of modern medicine would be impossible without the use of general anesthetics(GAs).Despite advancements in refining anesthesia approaches,the effects of GAs are not fully reversible upon GA withdrawal.Neu...The progress of modern medicine would be impossible without the use of general anesthetics(GAs).Despite advancements in refining anesthesia approaches,the effects of GAs are not fully reversible upon GA withdrawal.Neurocognitive deficiencies attributed to GA exposure may persist in neonates or endure for weeks to years in the elderly.Human studies on the mechanisms of the long-term adverse effects of GAs are needed to improve the safety of general anesthesia but they are hampered not only by ethical limitations specific to human research,but also by a lack of specific biological markers that can be used in human studies to safely and objectively study such effects.The latter can primarily be attributed to an insufficient understanding of the full range of the biological effects induced by GAs and the molecular mechanisms mediating such effects even in rodents,which are far more extensively studied than any other species.Our most recent experimental findings in rodents suggest that GAs may adversely affect many more people than is currently anticipated.Specifically,we have shown that anesthesia with the commonly used GA sevoflurane induces in exposed animals not only neuroendocrine abnormalities(somatic effects),but also epigenetic reprogramming of germ cells(germ cell effects).The latter may pass the neurobehavioral effects of parental sevoflurane exposure to the offspring,who may be affected even at levels of anesthesia that are not harmful to the exposed parents.The large number of patients who require general anesthesia,the even larger number of their future unexposed offspring whose health may be affected,and a growing number of neurodevelopmental disorders of unknown etiology underscore the translational importance of investigating the intergenerational effects of GAs.In this mini review,we discuss emerging experimental findings on neuroendocrine,epigenetic,and intergenerational effects of GAs.展开更多
Pancreatic cancer remains a leading cause of cancer-related death with few available therapies for advanced disease.Recently,patients with germline BRCA mutations have received increased attention due to advances in t...Pancreatic cancer remains a leading cause of cancer-related death with few available therapies for advanced disease.Recently,patients with germline BRCA mutations have received increased attention due to advances in the management of BRCA mutated ovarian and breast tumors.Germline BRCA mutations significantly increase risk of developing pancreatic cancer and can be found in up to 8%of patients with sporadic pancreatic cancer.In patients with germline BRCA mutations,platinum-based chemotherapies and poly(ADP-ribose)polymerase inhibitors are effective treatment options which may offer survival benefits.This review will focus on the molecular biology,epidemiology,and management of BRCA-mutated pancreatic cancer.Further-more,we will discuss future directions for this area of research and promising active areas of research.展开更多
Objective:Several studies have reported that the controlling nutritional status(CONUT)score is a prognostic predictor for survival among patients with different types of cancer.We assessed the prognostic value of chan...Objective:Several studies have reported that the controlling nutritional status(CONUT)score is a prognostic predictor for survival among patients with different types of cancer.We assessed the prognostic value of changes in the CONUT score during treatment and theΔCONUT-EBV DNA score in patients with advanced nasopharyngeal carcinoma(NPC).Methods:We retrospectively analyzed 433 patients with advanced NPC having no evidence of metastasis from January 2007 to June 2011;the patients underwent radical concurrent chemoradiotherapy(CCRT)at Sun Yat-sen University Cancer Center and were grouped based on theirΔCONUT andΔCONUT-EBV DNA scores.Kaplan-Meier curves were used to compare the patient outcomes according to the cut-offΔCONUT score and theΔCONUT-EBV DNA scoring system.Results:Among all patients,overall survival(OS)was independently predicted by a highΔCONUT score(P=0.031)and high EBV DNA(P<0.001).TheΔCONUT-EBV DNA score[OS area under the curve(AUC)=0.621;progression free survival(PFS)-AUC=0.612;distant metastasis-free survival(DMFS)-AUC=0.622]was more predictive of OS,PFS,and DMFS in patients with advanced NPC than theΔCONUT score(OS-AUC=0.547;PFS-AUC=0.533;DMFS-AUC=0.522)and pretreatment plasma EBV DNA levels alone(OS-AUC=0.600;PFS-AUC=0.591,DMFS-AUC=0.610).TheΔCONUT-EBV DNA score was significantly correlated with OS,PFS,and DMFS in patients with advanced NPC treated with CCRT.Conclusions:TheΔCONUT-EBV DNA score may be useful in clinical practice as a convenient biomarker for predicting the outcomes in patients with advanced NPC treated with CCRT.展开更多
The novel coronavirus (SARS-COV-2) is generally referred to as Covid-19 virus has spread to 213 countries with nearly 7 million confirmed cases and nearly 400,000 deaths. Such major outbreaks demand classification and...The novel coronavirus (SARS-COV-2) is generally referred to as Covid-19 virus has spread to 213 countries with nearly 7 million confirmed cases and nearly 400,000 deaths. Such major outbreaks demand classification and origin of the virus genomic sequence, for planning, containment, and treatment. Motivated by the above need, we report two alignment-free methods combing with CGR to perform clustering analysis and create a phylogenetic tree based on it. To each DNA sequence we associate a matrix then define distance between two DNA sequences to be the distance between their associated matrix. These methods are being used for phylogenetic analysis of coronavirus sequences. Our approach provides a powerful tool for analyzing and annotating genomes and their phylogenetic relationships. We also compare our tool to ClustalX algorithm which is one of the most popular alignment methods. Our alignment-free methods are shown to be capable of finding closest genetic relatives of coronaviruses.展开更多
In this study,an electrochemical DNA biosensor was developed using a straightforward methodology to investigate the interaction of indinavir with calf thymus double-stranded deoxyribonucleic acid(ctdsDNA)for the first...In this study,an electrochemical DNA biosensor was developed using a straightforward methodology to investigate the interaction of indinavir with calf thymus double-stranded deoxyribonucleic acid(ctdsDNA)for the first time.The decrease in the oxidation signals of deoxyguanosine(dGuo)and deoxyadenosine(dAdo),measured by differential pulse voltammetry,upon incubation with different concentrations of indinavir can be attributed to the binding mode of indinavir to ct-dsDNA.The currents of the dGuo and dAdo peaks decreased linearly with the concentration of indinavir in the range of 1.0 e10.0 mg/mL.The limit of detection and limit of quantification for indinavir were 0.29 and 0.98 mg/mL,respectively,based on the dGuo signal,and 0.23 and 0.78 mg/mL,respectively,based on the dAdo signal.To gain further insights into the interaction mechanism between indinavir and ct-dsDNA,spectroscopic measurements and molecular docking simulations were performed.The binding constant(Kb)between indinavir and ct-dsDNA was calculated to be 1.64108 M1,based on spectrofluorometric measurements.The obtained results can offer insights into the inhibitory activity of indinavir,which could help to broaden its applications.That is,indinavir can be used to inhibit other mechanisms and/or hallmarks of viral diseases.展开更多
Among inherited cardiac conditions,a special place is kept by cardiomyopathies(CMPs)and channelopathies(CNPs),which pose a substantial healthcare burden due to the complexity of the therapeutic management and cause ea...Among inherited cardiac conditions,a special place is kept by cardiomyopathies(CMPs)and channelopathies(CNPs),which pose a substantial healthcare burden due to the complexity of the therapeutic management and cause early mortality.Like other inherited cardiac conditions,genetic CMPs and CNPs exhibit incomplete penetrance and variable expressivity even within carriers of the same pathogenic deoxyribonucleic acid variant,challenging our understanding of the underlying pathogenic mechanisms.Until recently,the lack of accurate physiological preclinical models hindered the investigation of fundamental cellular and molecular mechanisms.The advent of induced pluripotent stem cell(iPSC)technology,along with advances in gene editing,offered unprecedented opportunities to explore hereditary CMPs and CNPs.Hallmark features of iPSCs include the ability to differentiate into unlimited numbers of cells from any of the three germ layers,genetic identity with the subject from whom they were derived,and ease of gene editing,all of which were used to generate“disease-in-a-dish”models of monogenic cardiac conditions.Functionally,iPSC-derived cardiomyocytes that faithfully recapitulate the patient-specific phenotype,allowed the study of disease mechanisms in an individual-/allele-specific manner,as well as the customization of therapeutic regimen.This review provides a synopsis of the most important iPSC-based models of CMPs and CNPs and the potential use for modeling disease mechanisms,personalized therapy and deoxyribonucleic acid variant functional annotation.展开更多
Cellular NDA and AgNOR Protein contents were evaluated byautomatic image analysis in tissue sections stained hy combined Feulgen-AgNOR staining method in 9 normal colonic mucosae, 45 colorectal adenomas and 27 adenoca...Cellular NDA and AgNOR Protein contents were evaluated byautomatic image analysis in tissue sections stained hy combined Feulgen-AgNOR staining method in 9 normal colonic mucosae, 45 colorectal adenomas and 27 adenocarcinomas. The results indicated that during the course that the normal colonical mucosa developed to colorectal adenocarcinoma via adenoma the DNA and AgNOR protein contents increased gradually and there were very significant correlationships between the DNA and the AgNOR protein contents of adenoma group and adenocarcinoma group. However, there were considerahle overlaping in the DNA or AgNOR Protein content and considerahle overlaping cases between adenoma and normal colonic mucosa groups and between adenoma and adenocarcinoma groups. But the overlaping scope in NDA and AgNOR Protein content and the number of overlaping cases were reduced significantly by assessing the correlationship between the DNA and AgNOR protein content. Therefore, it is much more reliable to distinguish colorectal adenomas from adnocarcinomas by using the correlationship between the cellular DNA and the AgNOR Protein contents in the same specimens.展开更多
文摘Introduction: Transitioning to more efficacious Antiretrovirals for HIV infected pregnant women and infant prophylaxis has reduced Mother to child transmission of HIV significantly. This study aimed to determine HIV infection status in HIVexposed infants who had their first DNA polymerase chain reaction test in our molecular Laboratory. Subjects, Materials and Methods: Dried Blood Spots for HIV DNA results from 5 states between 2009 and 2020 were analyzed in the PCR laboratory of the Federal Teaching Hospital, Gombe. Results: Nine thousand eight hundred and twenty-three Human Immunodeficiency Virus Deoxyribonucleic acid polymerase Chain Reaction results were analysed;4937 (50.2%) were males. During the study period, there was an overall declining trend in the mother-to-child transmission rate from 3.8% in 2009 to 1.0% in 2020. 6120 (62.3%) of HIV + mothers received Highly active antiretroviral therapy HAART before pregnancy. 7845 (76.2%) of the infants received Nevirapine prophylaxis. Dried blood spot samples were collected from 4077 (41.5%) at 6 - 8 weeks. 8438 (85.9%) received cotrimoxazole. 9469 (96.4%) were ever breastfed. Of the 9823 HIV DNA PCR results, 255 (2.6%) were positive while 69/4077 (1.7%) and 109/2662 (4.1%) were positive for HIV DNA at 6 - 8 weeks and > 12 weeks respectively. (p = 0.001). 86/747 (11.5%) of infants whose HIV-positive mothers received no ARVS were HIV DNA positive. (p = 0.001). 106/884 (12.0%) of infants who had no Antiretroviral prophylaxis had positive HIV DNA results;7/413 (1.7%) with Zidovudine/Nevirapine prophylaxis had positive results. (p = 0.001). 246/9469 (2.6%) of infants that were ever breastfed were positive for HIV DNA;11/354 (3.0%) that never breastfed had positive HIV DNA. Conclusion: Lack of maternal/infant ARVs and prolonged breastfeeding increased the risk of infant HIV infection.
基金Supported by the International Science and Technology Cooperation Projects,No. 2016YFE0107100Capital Special Research Project for Health Development,No. 2014-2-4012+3 种基金Beijing Natural Science Foundation,No. L172055 and No. 7192158National Ten-thousand Talent Programthe Fundamental Research Funds for the Central Universities,No. 3332018032CAMS Innovation Fund for Medical Science (CIFMS),No. 2017-I2M-4-003 and No. 2018-I2M-3-001。
文摘BACKGROUND Gastric cancer(GC) ranks as the third leading cause of cancer-related death worldwide. Epigenetic alterations contribute to tumor heterogeneity in early stages.AIM To identify the specific deoxyribonucleic acid(DNA) methylation sites that influence the prognosis of GC patients and explore the prognostic value of a model based on subtypes of DNA methylation.METHODS Patients were randomly classified into training and test sets. Prognostic DNA methylation sites were identified by integrating DNA methylation profiles and clinical data from The Cancer Genome Atlas GC cohort. In the training set, unsupervised consensus clustering was performed to identify distinct subgroups based on methylation status. A risk score model was built based on Kaplan-Meier, least absolute shrinkage and selector operation, and multivariate Cox regression analyses. A test set was used to validate this model.RESULTS Three subgroups based on DNA methylation profiles in the training set were identified using 1061 methylation sites that were significantly associated with survival. These methylation subtypes reflected differences in T, N, and M category, age, stage, and prognosis. Forty-one methylation sites were screened as specific hyper-or hypomethylation sites for each specific subgroup. Enrichment analysis revealed that they were mainly involved in pathways related to carcinogenesis, tumor growth, and progression. Finally, two methylation sites were chosen to generate a prognostic model. The high-risk group showed a markedly poor prognosis compared to the low-risk group in both the training [hazard ratio(HR) = 2.24, 95% confidence interval(CI): 1.28-3.92, P < 0.001] and test(HR = 2.12, 95%CI: 1.19-3.78, P = 0.002) datasets.CONCLUSION DNA methylation-based classification reflects the epigenetic heterogeneity of GC and may contribute to predicting prognosis and offer novel insights for individualized treatment of patients with GC.
文摘A retrospective study of flow cytometric measurements on paraffin-embedded tumor specimens from 188 patients with bladder tumor was conducted. The results were analyzed in combination with the morphological variation of bladder tumors. It was found that the DNA ploid pottern, degree of infiltration and the multiplicity of bladder tumor were closely related with tumor recurrence, among which the DNA ploid pattern was most significant. In aneuploid bladder tumors the recurrent rate and mean annual recurrence frequency were 76.7% and 1.46, and those in the diploid bladder tumors were 18.7% and 0.33 respectively. Aneuploid was the most indicative parameter of the recurrence in bladder tumors. In addition, according to the DNA ploid pattern and DNA index (DI), the aneuploid tumors in our group were divided into 4 types, namely, tetraploid tumors, npn-euploid with DI(?)1.5, non-euploid tumors with DI>1.5 and two-aneuploid tumors. The results showed that the recurrent rate of tetraploid tumors was relatively lower and it became higher and higher in the following order: non-euploid tumors with DI(?)1.5, non-euploid tumors with DI>1.5, and two-aneuploid tumors. This indicates that there are different biological behaviors in tumors with different ploid pattern. Finally, the correlation between DNA ploid pattern and tumor metastasis was also discussed.
基金Supported by the National Key Research and Development Program of China under Grant Nos 2016YFB0400104 and2016YFB0400301the National Natural Sciences Foundation of China under Grant No 61334002the National Science and Technology Major Project
文摘Gallium nitride- (GaN) based high electron mobility transistors (HEMTs) provide a good platform for biological detection. In this work, both Au-gated AlInN/GaN HEMT and AlGaN/GaN HEMT biosensors are fabricated for the detection of deoxyribonucleic acid (DNA) hybridization. The Au-gated AIInN/GaN HEMT biosensor exhibits higher sensitivity in comparison with the AlGaN/GaN HEMT biosensor. For the former, the drain-source current (VDS = 0.5 V) shows a clear decrease of 69μA upon the introduction of 1μmolL^-1 (μM) complimentary DNA to the probe DNA at the sensor area, while for the latter it is only 38 μA. This current reduction is a notable indication of the hybridization. The high sensitivity can be attributed to the thinner barrier of the AlInN/GaN heterostructure, which makes the two-dimensional electron gas channel more susceptible to a slight change of the surface charge.
文摘Touch deoxyribonucleic acid(DNA)refers to the DNA that is left behind from skin cells when a person touches or comes into contact with an object.In crimes where the identification of suspects becomes a challenge,touch DNA has been a proven investigative tool.The present study aims to provide a systematic review of the role of touch DNAin criminal cases which discusses the nature and importance of touch DNA evidence at crime scenes;various phenomena including the transfer and persistence of touched samples;different factors affecting the touch sample deposition and DNA shedding;the best recovery methods and collection of samples from different substrates;and the interpretation of profiles through advanced techniques that identify the suspects.The present study also aims to optimize standard protocols in the laboratories for touched samples appropriate to the substrates that improve the success rate of profiles from touched items.
基金supported by the Ministry of Public Security of China(2019GABJC15)the Institute of Forensic Science,Ministry of Public Security of China(2018JB007).
文摘Deoxyribonucleic acid(DNA)genetic markers and ribonucleic acid(RNA)molecular markers have been widely used in forensic practices including individual identification,parentage testing,body fluid identification,determination of the age of stains,and molecular pathological diagnosis.Variant information of biological evidence and their interrelation could be revealed by the integrated detection of DNA/RNA markers.The integrated detection workflow aims to simplify working procedures,reduce time consuming and save valuable samples collected from crime scenes.Next-generation sequencing(NGS)may be an effective method for integrated DNA/RNA detection.In this review,DNA/RNA co-extraction strategies,simultaneous detection methods based on capillary electrophoresis were summarized.Research on NGS-based integrated detection methods of DNA and RNA markers was reviewed to provide a reference for forensic medicine researches and applications.
文摘Aims: The purpose of this study was to determine the sex of primary and permanent tooth pulp tissue under different environmental conditions using deoxyribonucleic acid (DNA) analysis and the polymerase chain reaction (PCR) amplification method. Materials and Methods: For this study, 40 permanent and primary teeth (20 males and 20 females) that were scheduled for extraction were used. For 6 months, the teeth were divided into four groups of ten (5 males and 5 females) based on different environmental conditions. The pulp was extracted from each tooth, DNA was isolated using QIAGEN’s DNeasy Blood and Tissue Kit, and sex was determined using a PCR technique. Results: DNA was extracted from all 40 samples subjected to various environmental conditions, but sex was correctly determined in only 90% of the samples. Conclusions: PCR-based sex determination using primary and permanent teeth under different environmental conditions for up to 6 months is a reliable technique with high accuracy.
文摘DNA-linked 2D and 3D nano-assemblies find use in a diverse set of applications, ranging from DNA-origami in drug delivery and medical imaging, to DNA-linked nanoparticle structures for use in plasmonics and (bio)sensing. However, once these structures have been fully assembled, few options are available to modulate structure geometry. Here, we investigated the use of the polycation spermine to induce DNA collapse in small oligonucleotide-linked (54 bp) gold nanoparticle structures by monitoring shifts in the localized surface plasmon resonance (LSPR) peak and by comparing the data with finite-difference time-domain (FDTD) simulations. Our data shows that low concentrations of spermine can be applied to induce large changes in DNA conformation, leading to a significant reduction in interparticle distance (from - 25 to - 3 nm) and enhanced plasmonic coupling. The DNA collapse is near-instantaneous and reversible, and its application at low and high DNA densities is demonstrated with surface plasmon resonance imaging (SPRi), showing the potential of spermine to dynamically modulate distances and geometry in DNA-based nano-assemblies.
基金This work was supported by the Fundamental Research Funds for the Central Universities(No.2022XJHH02)the National Key Research and Development Program of China(No.2019YFC1907602).
文摘The exploitation of electrocatalysts with high activity and durability for HER is desirable for future energy systems,but it is still a challenge.NMPs have attracted increasing attentions,but the preparation process often needs toxic regents or dangerous reaction conditions.Herein,we develop a general green method to fabricate metal-rich NMPs anchored on NPG through pyrolyzing DNA cross-linked complexes.The obtained Ru_(2) P-NPG exhibits an ultrasmall overpotential of 7 mV at 10 mA cm^(2) and ultralow Tafel slope of 33 mV dec^(-1) in 1.0 mol L?1 KOH,even better than that of commercial Pt/C.In addition,Ru 2 P-NPG also shows low overpotentials of 29 and 78 mV in 0.5 mol L^(-1) H_(2)SO_(4) and 1.0 mol L^(-1) PBS,respectively.The superior activity can be attributed to the ultrafine dispersion of Ru 2 P nanoparticles for more accessible sites,more defects formed for abundant active sites,the two-dimensional plane structure for accelerated electron transfer and mass transport,as well as the regulation of electron distribution of the catalyst.Moreover,the synthetic method can also be applied to prepare other metal-rich noble metal phosphides(Pd_(3)P-NPG and Rh_(2)P-NPG),which also exhibits high activity for HER.This work provides an effective strategy for designing NMP-based electrocatalysts.
文摘Metastatic castrate-resistant prostate cancer remains a disease hard to cure,and for this reason predictive tools to monitor disease progression and therapy response are an urgent need.In this respect,liquid biopsy on circulating cell-free nucleic acids represents an interesting strategy based on robust data.The low invasiveness and the possibility to target circulating cell-free tumor deoxyribonucleic acid underline the high specificity,sensitivity and clinical usability of the technique.Moreover,it has been observed that the cell-free tumor deoxyribonucleic acid of metastatic castrate-resistant prostate cancer patients can be representative of the tumor heterogeneity.Cell-free tumor deoxyribonucleic acids express the same behaviors as mutations:Variation in gene copy number or the methylation rate of the tumor tissue.Recently,circulating cell-free ribonucleic acid molecules have emerged as interesting markers to stratify the disease.Due to high-throughput technologies,liquid biopsy on circulating cell-free nucleic acids will soon be utilized in the clinical management of metastatic castrate-resistant prostate cancer patients.
基金Project supported by the National Natural Science Foundation of China (Grant Nos. 62275216 and 61775181)the Innovation Capability Support Program of Shaanxi Province of China (Grant Nos. S2018-ZC-TD-0061 and TZ0393)the National Key Scientific Instrument and Equipment Development Projects of China (Grant No. 51927804)。
文摘Interactions between deoxyribonucleic acid(DNA) and metal ions are vital for maintaining life functions, however,there are still unsolved questions about its mechanisms. It is of great practical significance to study these issues for medical chip design, drug development, health care, etc. In this investigation, the conductivity properties of λ-DNA solutions with mono-/divalent metal ions(Na+, K^(+), Mg^(2+), and Ca^(2+)) are experimentally studied as they are electrically driven through a 5 μm microfluidic channel. Experimental data indicate that the conductivities of λ-DNA solutions with metal ions(M+/M2+) basically tend to reduce firstly and then increase as the voltage increases, of which the turning points varied with the metal ions. When the voltage surpasses turning points, the conductivity of λ-DNA-M+solutions increases with the concentration of metal ions, while that of λ-DNA-M^(2+)solutions decrease. Moreover, the conductivity of λ-DNA-M^(2+)solutions is always smaller than that of λ-DNA-M+solutions, and with high-concentration M^(2+), it is even smaller than that of the λ-DNA solution. The main reasons for the above findings could be attributed to the polarization of electrodes and different mechanisms of interactions between metal ions and λ-DNA molecules. This investigation is helpful for the precise manipulation of single DNA molecules in micro-/nanofluidic space and the design of new biomedical micro-/nanofluidic sensors.
基金Supported by the Postdoctoral Science Foundation of China,No.2005038300and the National Natural Science Foundation of China,No.30671028.
文摘BACKGROUND Efficient extraction of nucleic acids and proteins(ENAP)from cells is a prerequisite for precise annotation of gene function,and has become laboratory routine for revealing the mysteries of life.However,cell samples are often from different culture dishes,resulting in inevitable experimental errors and sometimes poor repeatability.AIM To explore a method to improve the efficiency of ENAP,minimizing errors in ENAP processes,enhancing the reliability and repeatability of subsequent experimental results.METHODS A protocol for the sequential isolation of RNA,DNA,and proteins from the same cultured HepG2 cells using RNAzol reagent is presented here.The first step involves culturing HepG2 cells to the exponential phase,followed by the sequential isolation of RNA,DNA,and proteins from the same cultured cells in the second step.The yield of nucleic acids and proteins is detected in the third step,and their purity and integrity are verified in the last step.RESULTS The procedure takes as few as 3-4 d from the start to quality verification and is highly efficient.In contrast to the existing kits and reagents,which are primarily based on independent isolation,this RNAzol reagent-based method is characterized by the sequential isolation of RNA,DNA,and proteins from the same cells,and therefore saves time,and has low cost and high efficiency.CONCLUSION The RNA,DNA,and proteins isolated using this method can be used for reverse transcription-polymerase chain reaction,polymerase chain reaction,and western blotting,respectively.
文摘The treatment and prognosis of malignant tumors are closely related to the time when the tumors are diagnosed;the earlier the diagnosis of the tumor,the better the prognosis.However,most tumors are not detected in the early stages of screening and diagnosis.It is of great clinical significance to study the correlation between multiple pathogeneses of tumors and explore simple,safe,specific,and sensitive molecular indicators for early screening,diagnosis,and prognosis.The Septin 9(SEPT9)gene has been found to be associated with a variety of human diseases,and it plays a role in the development of tumors.SEPT9 is a member of the conserved family of cytoskeletal GTPase,which consists of a P-loop-based GTP-binding domain flanked by a variable N-terminal region and a C-terminal region.SEPT9 is involved in many biological processes such as cytokinesis,polarization,vesicle trafficking,membrane reconstruction,deoxyribonucleic acid repair,cell migration,and apoptosis.Several studies have shown that SEPT9 may serve as a marker for early screening,diagnosis,and prognosis of some malignant tumors,and have the potential to become a new target for anti-cancer therapy.This article reviews the progress in research on the SEPT9 gene in early screening,diagnosis,and prognosis of tumors.
基金Supported by National Institutes of Health,No.R01NS091542National Natural Science Foundation of China,No.81771149,No.U1704165。
文摘The progress of modern medicine would be impossible without the use of general anesthetics(GAs).Despite advancements in refining anesthesia approaches,the effects of GAs are not fully reversible upon GA withdrawal.Neurocognitive deficiencies attributed to GA exposure may persist in neonates or endure for weeks to years in the elderly.Human studies on the mechanisms of the long-term adverse effects of GAs are needed to improve the safety of general anesthesia but they are hampered not only by ethical limitations specific to human research,but also by a lack of specific biological markers that can be used in human studies to safely and objectively study such effects.The latter can primarily be attributed to an insufficient understanding of the full range of the biological effects induced by GAs and the molecular mechanisms mediating such effects even in rodents,which are far more extensively studied than any other species.Our most recent experimental findings in rodents suggest that GAs may adversely affect many more people than is currently anticipated.Specifically,we have shown that anesthesia with the commonly used GA sevoflurane induces in exposed animals not only neuroendocrine abnormalities(somatic effects),but also epigenetic reprogramming of germ cells(germ cell effects).The latter may pass the neurobehavioral effects of parental sevoflurane exposure to the offspring,who may be affected even at levels of anesthesia that are not harmful to the exposed parents.The large number of patients who require general anesthesia,the even larger number of their future unexposed offspring whose health may be affected,and a growing number of neurodevelopmental disorders of unknown etiology underscore the translational importance of investigating the intergenerational effects of GAs.In this mini review,we discuss emerging experimental findings on neuroendocrine,epigenetic,and intergenerational effects of GAs.
文摘Pancreatic cancer remains a leading cause of cancer-related death with few available therapies for advanced disease.Recently,patients with germline BRCA mutations have received increased attention due to advances in the management of BRCA mutated ovarian and breast tumors.Germline BRCA mutations significantly increase risk of developing pancreatic cancer and can be found in up to 8%of patients with sporadic pancreatic cancer.In patients with germline BRCA mutations,platinum-based chemotherapies and poly(ADP-ribose)polymerase inhibitors are effective treatment options which may offer survival benefits.This review will focus on the molecular biology,epidemiology,and management of BRCA-mutated pancreatic cancer.Further-more,we will discuss future directions for this area of research and promising active areas of research.
基金This work was supported by grants from the National Key R&D Program of China(Grant Nos.2017YFC1309003 and 2017YFC0908500)the National Natural Science Foundation of China(Grant Nos.81425018,81672868,and 81802775)+10 种基金the Sci-Tech Project Foundation of Guangzhou City(Grant No.201707020039)the Sun Yat-sen University Clinical Research 5010 Program,the Special Support Plan of Guangdong Province(Grant No.2014TX01R145)the Natural Science Foundation of Guangdong Province(Grant Nos.2017A030312003 and 2018A0303131004)the Natural Science Foundation of Guangdong Province for Distinguished Young Scholar(Grant No.2018B030306001)the Sci-Tech Project Foundation of Guangdong Province(Grant No.2014A020212103)the Health&Medical Collaborative Innovation Project of Guangzhou City(Grant Nos.201400000001 and 201803040003)the Pearl River S&T Nova Program of Guangzhou(Grant No.201806010135)the Planned Science and Technology Project of Guangdong Province(Grant No.2019B020230002)the National Science&Technology Pillar Program during the Twelfth Five-year Plan Period(Grant No.2014BAI09B10)the Natural Science Foundation of Guangdong Province(Grant No.2017A030312003Fundamental Research Funds for the Central Universities。
文摘Objective:Several studies have reported that the controlling nutritional status(CONUT)score is a prognostic predictor for survival among patients with different types of cancer.We assessed the prognostic value of changes in the CONUT score during treatment and theΔCONUT-EBV DNA score in patients with advanced nasopharyngeal carcinoma(NPC).Methods:We retrospectively analyzed 433 patients with advanced NPC having no evidence of metastasis from January 2007 to June 2011;the patients underwent radical concurrent chemoradiotherapy(CCRT)at Sun Yat-sen University Cancer Center and were grouped based on theirΔCONUT andΔCONUT-EBV DNA scores.Kaplan-Meier curves were used to compare the patient outcomes according to the cut-offΔCONUT score and theΔCONUT-EBV DNA scoring system.Results:Among all patients,overall survival(OS)was independently predicted by a highΔCONUT score(P=0.031)and high EBV DNA(P<0.001).TheΔCONUT-EBV DNA score[OS area under the curve(AUC)=0.621;progression free survival(PFS)-AUC=0.612;distant metastasis-free survival(DMFS)-AUC=0.622]was more predictive of OS,PFS,and DMFS in patients with advanced NPC than theΔCONUT score(OS-AUC=0.547;PFS-AUC=0.533;DMFS-AUC=0.522)and pretreatment plasma EBV DNA levels alone(OS-AUC=0.600;PFS-AUC=0.591,DMFS-AUC=0.610).TheΔCONUT-EBV DNA score was significantly correlated with OS,PFS,and DMFS in patients with advanced NPC treated with CCRT.Conclusions:TheΔCONUT-EBV DNA score may be useful in clinical practice as a convenient biomarker for predicting the outcomes in patients with advanced NPC treated with CCRT.
文摘The novel coronavirus (SARS-COV-2) is generally referred to as Covid-19 virus has spread to 213 countries with nearly 7 million confirmed cases and nearly 400,000 deaths. Such major outbreaks demand classification and origin of the virus genomic sequence, for planning, containment, and treatment. Motivated by the above need, we report two alignment-free methods combing with CGR to perform clustering analysis and create a phylogenetic tree based on it. To each DNA sequence we associate a matrix then define distance between two DNA sequences to be the distance between their associated matrix. These methods are being used for phylogenetic analysis of coronavirus sequences. Our approach provides a powerful tool for analyzing and annotating genomes and their phylogenetic relationships. We also compare our tool to ClustalX algorithm which is one of the most popular alignment methods. Our alignment-free methods are shown to be capable of finding closest genetic relatives of coronaviruses.
文摘In this study,an electrochemical DNA biosensor was developed using a straightforward methodology to investigate the interaction of indinavir with calf thymus double-stranded deoxyribonucleic acid(ctdsDNA)for the first time.The decrease in the oxidation signals of deoxyguanosine(dGuo)and deoxyadenosine(dAdo),measured by differential pulse voltammetry,upon incubation with different concentrations of indinavir can be attributed to the binding mode of indinavir to ct-dsDNA.The currents of the dGuo and dAdo peaks decreased linearly with the concentration of indinavir in the range of 1.0 e10.0 mg/mL.The limit of detection and limit of quantification for indinavir were 0.29 and 0.98 mg/mL,respectively,based on the dGuo signal,and 0.23 and 0.78 mg/mL,respectively,based on the dAdo signal.To gain further insights into the interaction mechanism between indinavir and ct-dsDNA,spectroscopic measurements and molecular docking simulations were performed.The binding constant(Kb)between indinavir and ct-dsDNA was calculated to be 1.64108 M1,based on spectrofluorometric measurements.The obtained results can offer insights into the inhibitory activity of indinavir,which could help to broaden its applications.That is,indinavir can be used to inhibit other mechanisms and/or hallmarks of viral diseases.
文摘Among inherited cardiac conditions,a special place is kept by cardiomyopathies(CMPs)and channelopathies(CNPs),which pose a substantial healthcare burden due to the complexity of the therapeutic management and cause early mortality.Like other inherited cardiac conditions,genetic CMPs and CNPs exhibit incomplete penetrance and variable expressivity even within carriers of the same pathogenic deoxyribonucleic acid variant,challenging our understanding of the underlying pathogenic mechanisms.Until recently,the lack of accurate physiological preclinical models hindered the investigation of fundamental cellular and molecular mechanisms.The advent of induced pluripotent stem cell(iPSC)technology,along with advances in gene editing,offered unprecedented opportunities to explore hereditary CMPs and CNPs.Hallmark features of iPSCs include the ability to differentiate into unlimited numbers of cells from any of the three germ layers,genetic identity with the subject from whom they were derived,and ease of gene editing,all of which were used to generate“disease-in-a-dish”models of monogenic cardiac conditions.Functionally,iPSC-derived cardiomyocytes that faithfully recapitulate the patient-specific phenotype,allowed the study of disease mechanisms in an individual-/allele-specific manner,as well as the customization of therapeutic regimen.This review provides a synopsis of the most important iPSC-based models of CMPs and CNPs and the potential use for modeling disease mechanisms,personalized therapy and deoxyribonucleic acid variant functional annotation.
文摘Cellular NDA and AgNOR Protein contents were evaluated byautomatic image analysis in tissue sections stained hy combined Feulgen-AgNOR staining method in 9 normal colonic mucosae, 45 colorectal adenomas and 27 adenocarcinomas. The results indicated that during the course that the normal colonical mucosa developed to colorectal adenocarcinoma via adenoma the DNA and AgNOR protein contents increased gradually and there were very significant correlationships between the DNA and the AgNOR protein contents of adenoma group and adenocarcinoma group. However, there were considerahle overlaping in the DNA or AgNOR Protein content and considerahle overlaping cases between adenoma and normal colonic mucosa groups and between adenoma and adenocarcinoma groups. But the overlaping scope in NDA and AgNOR Protein content and the number of overlaping cases were reduced significantly by assessing the correlationship between the DNA and AgNOR protein content. Therefore, it is much more reliable to distinguish colorectal adenomas from adnocarcinomas by using the correlationship between the cellular DNA and the AgNOR Protein contents in the same specimens.