Objective To investigate the mechanistic basis for the anti-proliferation and anti-invasion effect of tumor necrosis factor-related apoptosis-induced ligand(TRAIL)and celastrol combination treatment(TCCT)in glioblasto...Objective To investigate the mechanistic basis for the anti-proliferation and anti-invasion effect of tumor necrosis factor-related apoptosis-induced ligand(TRAIL)and celastrol combination treatment(TCCT)in glioblastoma cells.Methods Cell counting kit-8 was used to detect the effects of different concentrations of celastrol(0-16µmol/L)and TRAIL(0-500 ng/mL)on the cell viability of glioblastoma cells.U87 cells were randomly divided into 4 groups,namely control,TRAIL(TRAIL 100 ng/mL),Cel(celastrol 0.5µmol/L)and TCCT(TRAIL 100 ng/mL+celastrol 0.5µmol/L).Cell proliferation,migration,and invasion were detected by colony formation,wound healing,and Transwell assays,respectively.Quantitative reverse transcription polymerase chain reaction and Western blotting were performed to assess the levels of epithelial-mesenchymal transition(EMT)markers(zona occludens,N-cadherin,vimentin,zinc finger E-box-binding homeobox,Slug,and β-catenin).Wnt pathway was activated by lithium chloride(LiCl,20 mol/L)and the mechanism for action of TCCT was explored.Results Celastrol and TRAIL synergistically inhibited the proliferation,migration,invasion,and EMT of U87 cells(P<0.01).TCCT up-regulated the expression of GSK-3β and down-regulated the expression of β-catenin and its associated proteins(P<0.05 or P<0.01),including c-Myc,Cyclin-D1,and matrix metalloproteinase(MMP)-2.In addition,LiCl,an activator of the Wnt signaling pathway,restored the inhibitory effects of TCCT on the expression of β-catenin and its downstream genes,as well as the migration and invasion of glioblastoma cells(P<0.05 or P<0.01).Conclusions Celastrol and TRAIL can synergistically suppress glioblastoma cell migration,invasion,and EMT,potentially through inhibition of Wnt/β-catenin pathway.This underlies a novel mechanism of action for TCCT as an effective therapy for glioblastoma.展开更多
Collagen scaffolds possess a three-dimensional porous structure that provides sufficient space for cell growth and proliferation,the passage of nutrients and oxygen,and the discharge of metabolites.In this study,a por...Collagen scaffolds possess a three-dimensional porous structure that provides sufficient space for cell growth and proliferation,the passage of nutrients and oxygen,and the discharge of metabolites.In this study,a porous collagen scaffold with axially-aligned luminal conduits was prepared.In vitro biocompatibility analysis of the collagen scaffold revealed that it enhances the activity of neural stem cells and promotes cell extension,without affecting cell differentiation.The collagen scaffold loaded with neural stem cells improved the hindlimb motor function in the rat model of T8 complete transection and promoted nerve regeneration.The collagen scaffold was completely degraded in vivo within 5 weeks of implantation,exhibiting good biodegradability.Rectal temperature,C-reactive protein expression and CD68 staining demonstrated that rats with spinal cord injury that underwent implantation of the collagen scaffold had no notable inflammatory reaction.These findings suggest that this novel collagen scaffold is a good carrier for neural stem cell transplantation,thereby enhancing spinal cord repair following injury.This study was approved by the Animal Ethics Committee of Nanjing Drum Tower Hospital(the Affiliated Hospital of Nanjing University Medical School),China(approval No.2019AE02005)on June 15,2019.展开更多
Background: Sheep is important in the socio-economic lives of people around the world. It is estimated that more than half of our once common livestock breeds are now endangered. Since genetic characterization of Nige...Background: Sheep is important in the socio-economic lives of people around the world. It is estimated that more than half of our once common livestock breeds are now endangered. Since genetic characterization of Nigerian sheep is still lacking, we analyzed ten morphological traits on 402 animals and 15 microsatellite DNA markers in 384 animals of the 4 Nigerian sheep breeds to better understand genetic diversity for breeding management and germplasm conservation. Results: Morphological traits of Uda and Balami were significantly (P < 0.05) higher than Yankasa, which were both higher than West African Dwarf (WAD) sheep. Stepwise discriminant analysis showed tail length, rump height, chest girth, ear length and chest depth as the most discriminating variables for classification. Mahalanobis distances show the least differentiation between Uda and Balami and the largest between WAD and Balami sheep. While 93.3% of WAD sheep were correctly assigned to their source genetic group, 63.9% of Yankasa, 61.2% of Balami and 45.2% of Uda were classified correctly by nearest neighbour discriminant analysis. The overall high Polymorphism Information Content (PIC) of all microsatellite markers ranged from 0.751 to 0.927 supporting their use in genetic characterization. Expected heterozygosity was high for all loci (0.783 to 0.93). Mean heterozygote deficiency across all populations (0.171 to 0.534) possibly indicate significant inbreeding (P < 0.05). Mean values for FST , FIT and FIS statistics across all loci were 0.088, 0.394 and 0.336 respectively. Yankasa and Balami are the most closely related breeds (DA = 0.184) while WAD and Balami are the farthest apart breeds (DA = 0.665), which is coincident with distance based on morphological analysis and population structure assessed by STRUCTURE. Conclusions: These results suggest that within-breed genetic variation in Nigerian sheep is higher than between-breeds and may be a valuable tool for genetic improvement and conservation. The higher genetic variability in Yankasa suggests the presence of unique ancestral alleles reflecting the presence of certain functional genes which may result in better adaptability in more agro-ecological zones of Nigeria. These genetic characteristics are potentially useful in planning improvement and conservation strategies in Nigerian indigenous sheep.展开更多
In order to explain the direction,speed and specificity of cell signaling a dual pathway hypothesis is proposed.In this hypothesis the physical pathway is coupled to the biochemical pathway.As an example,the propagati...In order to explain the direction,speed and specificity of cell signaling a dual pathway hypothesis is proposed.In this hypothesis the physical pathway is coupled to the biochemical pathway.As an example,the propagation of a mechanical wave along the cytoskeleton components is discussed.展开更多
Dermatophytes were earlier reported to respond well to anti-fungal agents;however, an upsurge in resistance with the high cost of these agents increased the use of medicinal plants for treatment. This study investigat...Dermatophytes were earlier reported to respond well to anti-fungal agents;however, an upsurge in resistance with the high cost of these agents increased the use of medicinal plants for treatment. This study investigated the sensitivity pattern of dermatophytes to oral anti-fungal drugs and aqueous leaf extract of the plant, <em>Acacia nilotica</em>. The extract was tested against seven strains of dermatophytes <em>Arthroderma otae</em>, <em>Trichophyton interdigitale</em>, <em>Trichophyton mentagrophyte</em>, <em>Microsporum ferrugineum</em>, <em>Arthroderma vespertilii</em>, <em>Arthroderma quadrifidum</em>, and <em>Arthroderma multifidum</em>, previously isolated from diabetic patients. The minimum inhibitory and fungicidal concentrations of the plant extracts and the standard antifungal agents were evaluated using modifications of the broth macro dilution method of the National Committee for Clinical Laboratory Standards M38-A2 protocol. There was a significant difference in the Minimum Inhibitory concentrations (MIC) of the dermatophytes to the three antifungal drugs tested (p < 0.001). The dermatophytes were mostly susceptible to itraconazole followed by Nystatin. All the dermatophytes tested were resistant to griseofulvin. <em>Acacia nilotica</em> had an inhibitory effect on all the dermatophytes tested, and showed anti-fungal activity in a dose-dependent relationship between 0.625 - 1.25 mg/ml. Though the inhibitions of the dermatophytes were significantly higher with the standard anti-fungal drugs as compared to the plant extract (p < 0.001);however, the dermatophyte, <em>Arthroderma quadrifidum</em>, which was resistant to all the anti-fungal drugs, had the highest inhibition with <em>A. nilotica</em>. Some circulating dermatophyte strains in Nigeria are griseofulvin and/or itraconazole resistant which may influence the spread of infection and <em>A. nilotica</em> aqueous leaf extract showed a strong anti-dermatophytic activity.展开更多
<strong>Background:</strong> Cisplatin, a chemotherapeutic agent, is widely used in the treatment of malignant tumors. Nephrotoxicity, especially acute kidney injury (AKI), is the most common and severe ad...<strong>Background:</strong> Cisplatin, a chemotherapeutic agent, is widely used in the treatment of malignant tumors. Nephrotoxicity, especially acute kidney injury (AKI), is the most common and severe adverse reaction of cisplatin. Resveratrol and ginsenoside Rg1, two natural products, have been found to have renal protective effects. However, the effects and the mechanisms in cisplatin-induced AKI need further investigation. <strong>Methods:</strong> The mouse models of cisplatin-induced AKI and several treatment groups were established. Male C57BL/6 mice were divided into five groups: saline control group, cisplatin injury group, resveratrol treatment group, Rg1 treatment group, resveratrol and Rg1 combined treatment group. Serological analysis of serum urea nitrogen was aimed to reflect the function of kidney, and histological analysis of renal tissue sections was aimed to assess the damage of proximal convoluted tubules. The expression levels of autophagy-related proteins Beclin 1 and LC3 were detected by western blotting and qRT-PCR respectively. <strong>Results:</strong> The renal function was improved and renal damage was alleviated in Rg1 and resveratrol alone or combined treatment groups compared with the cisplatin injury group. For the mechanism, treatment with Rg1 and resveratrol alone or in combination decreased the expressions of Beclin 1 both at protein and mRNA levels, decreased LC3II/I protein levels, indicating that autophagy was inhibited by treatment with Rg1 and resveratrol alone or in combination. <strong>Conclusion:</strong> Resveratrol and Rg1 alleviated the kidney damage caused by cisplatin, and reduced autophagy was involved in the renoprotective effects of resveratrol and Rg1 against cisplatin-induced AKI. This study may provide new evidence to alleviate cisplatin-induced AKI.展开更多
Esophageal squamous cell cancer(EScC)is one of the malignant tumors with high morbidity and mortality all over the world.^(1) In recent years,combined chemotherapy has gradually been the effective treatment method for...Esophageal squamous cell cancer(EScC)is one of the malignant tumors with high morbidity and mortality all over the world.^(1) In recent years,combined chemotherapy has gradually been the effective treatment method for EscC patients.Therefore,it is imperative to explore potential therapeutic targets for the treatment of EsCC.We previously reported a high-frequency amplification of pyrimidine metabolic pathway-related genes in EsCC tissues.展开更多
Since the outbreak of the novel corona virus disease 2019(COVID-19)at the end of 2019,specific antiviral drugs have been lacking.A Chinese patent medicine Toujiequwen granules has been promoted in the treatment of COV...Since the outbreak of the novel corona virus disease 2019(COVID-19)at the end of 2019,specific antiviral drugs have been lacking.A Chinese patent medicine Toujiequwen granules has been promoted in the treatment of COVID-19.The present study was designed to reveal the molecular mechanism of Toujiequwen granules against COVID-19.A network pharmacological method was applied to screen the main active ingredients of Toujiequwen granules.Network analysis of 149 active ingredients and 330 drug targets showed the most active ingredient interacting with many drug targets is quercetin.Drug targets most ffected by the active ingredients were PTGS2,PTGS1,and DPP4.Drug target disease enrichment analysis showed drug targets were significantly enriched in cardiovascular diseases and digestive tract diseases.An"active ingredient-target-disease"network showed that 57 active ingredients from Toujiequwen granules interacted with 15 key targets of COVID-19.There were 53 ingredients that could act on DPP4,suggesting that DPP4 may become a potential new key target for the treatment of COVID-19.GO analysis results showed that key targets were mainly enriched in the cellular response to lipopolysaccharide,cytokine activity and other functions.KEGG analysis showed they were mainly concentrated in viral protein interaction with cytokine and cytokine receptors and endocrine resistance pathway.The evidence suggests that Toujiequwen granules might play an effective role by improving the symptoms of underlying diseases in patients with COVID-19 and multi-target interventions against mutiple signaling pathways related to the pathogenesis of COVID-19.展开更多
AIM: To identify disease-causing mutation in a congenital cataract family using enrichment of targeted genes combined with next-generation sequencing.· METHODS: A total of 371 known genes related to inherited eye...AIM: To identify disease-causing mutation in a congenital cataract family using enrichment of targeted genes combined with next-generation sequencing.· METHODS: A total of 371 known genes related to inherited eye diseases of the proband was selected and captured, followed by high-throughput sequencing. The sequencing data were analyzed by established bioinformatics pipeline. Validation was performed by Sanger sequencing.·RESULTS: A recurrent heterozygous non-synonymous mutation c.130 G >A(p.V44M) in the GJA3 gene was identified in the proband. The result was confirmed by Sanger sequencing. The mutation showed co-segregation with the disease phenotype in the family but was not detected in unaffected controls.·CONCLUSION: Targeted exome sequencing is a rapid,high-throughput and cost-efficient method for screening known genes and could be applied to the routine gene diagnosis of congenital cataract.展开更多
3β-Hydroxysteroid-Δ24 reductase(DHCR24) is a multifunctional enzyme that localizes to the endoplasmic reticulum and has neuroprotective and cholesterol-synthesizing activities. DHCR24 overexpression confers neuropro...3β-Hydroxysteroid-Δ24 reductase(DHCR24) is a multifunctional enzyme that localizes to the endoplasmic reticulum and has neuroprotective and cholesterol-synthesizing activities. DHCR24 overexpression confers neuroprotection against apoptosis caused by amyloid β deposition. The present study aimed to construct two recombinant adenoviruses driving DHCR24 expression specifically in neurons. Two SYN1 promoter DNA fragments were obtained from human(h) and rat(r). Recombinant Ad-r(h)SYN1-DHCR24 was transfected into AD-293, N2A(mouse neuroblastoma), and MIN6(mouse pancreatic carcinoma) cells. Western blot analysis showed DHCR24 was specially expressed in 293 and N2A cells, but no specific band was found in MIN6 cells. This demonstrates that the recombinant adenoviruses successfully express DHCR24, and no expression is observed in non-neuronal cells. TUNEL assay results showed apoptosis was inhibited in adenovirus-transfected neurons. Detecting reactive oxygen species by immunofluorescence, we found that adenovirus transfection inhibits apoptosis through scavenging excess reactive oxygen species. Our findings show that the recombinant DHCR24 adenoviruses induce neuron-specific DHCR24 expression, and thereby lay the foundation for further studies on DHCR24 gene therapy for Alzheimer's disease.展开更多
In view of increasing lead pollution(Pb^(2+)) of coastal waters, the compensatory abilities of holothurians need to be assessed. The goal of the work is to clarify the functional and phenotypical differences between t...In view of increasing lead pollution(Pb^(2+)) of coastal waters, the compensatory abilities of holothurians need to be assessed. The goal of the work is to clarify the functional and phenotypical differences between two types of phagocytes(P1 and P2) in Eupentacta fraudatrix exposed to Pb(NO_3)_2. It has been shown that 2 mg L^(-1) lead exposure for 48 h increases the number of P2 phagocytes as compared to P1 cells, does not significantly affect cell viability in both P1 and P2 phagocyte fractions, and significantly enhances chromatin condensation in P2 but not in P1 phagocytes. A lead concentration of 4 mg L^(-1) increases the number of P1 phagocytes compared to that of P2 type, and does not change cell viability and chromatin condensation in P1 phagocytes. In the P2 type, it decreases cell viability and does not influence the level of apoptosis. The protection against lead-induced apoptosis is apparently mediated by the activities of antioxidant enzymes, especially glutathione S-transferase. The differences in labeling cell surface receptors of P1 and P2 phagocytes by plant lectins also indicate the specific phenotypic properties of these cells. The results clarify the potential and GSH-dependent mechanisms of immune adaptation in holothurians that have been shortly exposed to lead at concentrations close to the maximum environmentally relevant level in coastal waters. Additionally, P1 and P2 phagocytes are first shown to have different functions and phenotypes during the response to lead, which indicates the complexity of the phagocytic system in holothurians and contributes to understanding the immunity evolution.展开更多
OBJECTIVE This study was conducted to explore the effect of Rg3 on inhibition of proliferation and induction of apoptosis in bladder cancer cells. METHODS The EJ bladder cancer cell line was treated with Rg3 at variou...OBJECTIVE This study was conducted to explore the effect of Rg3 on inhibition of proliferation and induction of apoptosis in bladder cancer cells. METHODS The EJ bladder cancer cell line was treated with Rg3 at various concentrations. Cell proliferation was measured by the MTT assay. Morphological changes in the cells were observed by fluorescent staining using Hoechst 33258. The cell cycle and apoptotic rate were analyzed by flow cytometry (FCM) and the expression of caspase-3 in cells was detected by immunocytochemistry. DMA ladder analysis was conducted by agarose gel electrophoresis. RESULTS Rg3 inhibited proliferation of EJ cells in a concentration-dependent manner, resulting in an IC50 for Rg3 at 48 h of 125.5μg/ml. When treated with 150μg/ml of Rg3 for 24 h and 48 h, the cells showed apoptotic morphological characteristics including condensed chromatin, nuclear fragmentation, apoptotic bodies and bright fluorescent granules as well as a higher caspase-3 expression. The FCM assay indicated that Rg3 altered the cell cycle and induced apoptosis of the EJ cells, when treated for 24 h and 48 h with 75μg/ml of Rg3 as well as for 48 h with 150μg/ml. The percentages of cells in the S phase and the G2/M transition were increased, whereas the percentages of cells in the G0-G1 transition were decreased. The apoptotic rates were increased from (1.05±0.17)% in the control group cells to (8.41±0.98)%,(18.57±2.20)% and (33.98±1.64)% respectively. Significant changes in the DNA ladders, showed that the effects of Rg3 were displayed in a dose and time dependent manner. CONCLUSION The results suggest that Ginsenoside Rg3 exerts an inhibitory effect on proliferation of EJ cells by inducing apoptosis.展开更多
Indiscriminate handling and disposal of industrial effluents into the environment represents one of the major sources of environmental pollution which invariably affect plants, animals and humans. This study assessed ...Indiscriminate handling and disposal of industrial effluents into the environment represents one of the major sources of environmental pollution which invariably affect plants, animals and humans. This study assessed heavy metal concentration in soils and plants around industries in Agbara industrial estate, Ogun State, Nigeria. Soil and plant samples were collected from four industries and analyzed for lead (Pb), cadmium (Cd), copper (Cu), chromium (Cr) and nickel (Ni). The pH, organic matter content and cation exchange capacity of the soil samples, as well as bioaccumulation factor (BAF) and translocation factor (TF) of the plant samples were examined. The heavy metal concentration order of the soil and plant samples was Pb ?1, 50 mg kg?1, 10 mg kg?1 and 50 mg kg?1 respectively) while Cd was above WHO tolerance limit (3 mg kg?1). Also, Pb, Cd, Cu, and Cr in most plant samples were above WHO tolerance limits (10 mg kg?1, 0.30 mg kg?1, 10 mg kg?1 and 1.5 mg kg?1 respectively). Statistical differences (P Cyperus iria, Alternanthera sessilis, C. esculentus, A. brasiliana, and Megathyrsus maximus are probable accumulators of heavy metals.展开更多
Pigmentation plays important adaptation and physiological efficiency roles in animals. In the sequence of a 648 bp fragment representing intron 1, exon 2, and part of intron 2 of the MLPH mammalian pigmentation gene, ...Pigmentation plays important adaptation and physiological efficiency roles in animals. In the sequence of a 648 bp fragment representing intron 1, exon 2, and part of intron 2 of the MLPH mammalian pigmentation gene, we identified a novel g.469C> G mutation in intron 2, and genotyped it in 266 Nigerian goats using PCR-RFLP analysis. The C allele had frequencies of 0.9625, 0.9804 and 0.97405 in West African Dwarf (WAD),Sahel(SH) and Red Sokoto (RS) breeds, respectively. The G allele was the highest in WAD (0.0375), followed by RS (0.02595), and then SH (0.0196). Overall low FIS and FST and high Nm values demonstrate little differentiation within and among the goat breeds at this intronic locus. This g.469C> G polymorphism in MLPH gene is the first in any goat breed and also first in Nigerian goats. Our results suggest that this intronic SNP locus is maintained at Hardy-Weinberg equilibrium (P < 0.05) and the lack of association of this SNP with coat color may indicate its neutrality in goats.展开更多
Tumor is a serious disease that threatens human health and has a high mortality. Chemotherapy is the most commonly used treatment, but it has a lot of side effects due to its toxicity. It has been found that ginsenosi...Tumor is a serious disease that threatens human health and has a high mortality. Chemotherapy is the most commonly used treatment, but it has a lot of side effects due to its toxicity. It has been found that ginsenosides exert an effective antitumor role. Ginsenosides are a class of triterpenoid saponins primarily found in the plant genus Panax. Many monomer components are studied, the most often investigated are Rg3, and Rh2, etc. Reports have shown that ginsenosides can inhibit tumor cells by suppressing proliferation and metastasis, and promoting apoptosis. In addition, ginsenosides can enhance sensitivity to conventional chemotherapeutic drugs. In this review, the recent articles about anti-tumor of ginsenosides were reviewed to promote the further development of anti-tumor therapy.展开更多
Allopolyploid oilseed rape(Brassica napus)is an important oil crop and vegetable.However,the latest version of its reference genome,with collapsed duplications,gaps,and other issues,prevents comprehensive genomic anal...Allopolyploid oilseed rape(Brassica napus)is an important oil crop and vegetable.However,the latest version of its reference genome,with collapsed duplications,gaps,and other issues,prevents comprehensive genomic analysis.Herein,we report a gap-free assembly of the rapeseed cv.Xiang5A genome using a combination of ONT(Oxford Nanopore Technologies)ultra-long reads,PacBio high-fidelity reads,and Hi-C datasets.It includes gap-free assemblies of all 19 chromosomes and telomere-to-telomere assemblies of eight chromosomes.Compared with previously published genomes of B.napus,our gap-free genome,with a contig N50 length of 50.70 Mb,has complete assemblies of 9 of 19 chromosomes without manual intervention,and greatly improves contiguity and completeness,thereby representing the highest quality genome assembly to date.Our results revealed that B.napus Xiang5A underwent nearly complete triplication and allotetraploidy relative to Arabidopsis thaliana.Using the gap-free assembly,we found that 917 flowering-related genes were affected by structural variation,including BnaA03.VERNALIZATION INSENSITIVE 3 and BnaC04.HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENES 1.These genes may play crucial roles in regulating flowering time and facilitating the adaptation of Xiang5A in the Yangtze River Basin of China.This reference genome provides a valuable genetic resource for rapeseed functional genomic studies and breeding.展开更多
Circular RNAs (circRNAs) are a special class of single-stranded RNA molecules with covalently closed loops widely expressed in eukaryotic organisms. CircRNAs have long been considered to play important roles in variou...Circular RNAs (circRNAs) are a special class of single-stranded RNA molecules with covalently closed loops widely expressed in eukaryotic organisms. CircRNAs have long been considered to play important roles in various physiological and pathological processes as non-coding RNAs. However, circRNAs have recently garnered considerable attention due to their ability to be translated into peptides/proteins via internal ribosome entry site- or N6-methyladenosine-mediated pathways or rolling translation mechanisms. Furthermore, dysregulation of translatable circRNAs and their encoded proteins has been associated with developing and progressing diseases such as cancer. This review aims to summarize the driving mechanisms of circRNA translation and the available strategies in circRNA translation research. The main focus is on the emerging biological functions of translatable circRNAs, their regulatory mechanisms, and potential clinical applications in human diseases to provide new perspectives on disease diagnosis, prognosis, and targeted therapy.展开更多
Parthenogenetic embryos,created by activation and diploidization of oocytes,arrest at mid-gestation for defective paternal imprints,which impair placental development.Also,viable offspring has not been obtained withou...Parthenogenetic embryos,created by activation and diploidization of oocytes,arrest at mid-gestation for defective paternal imprints,which impair placental development.Also,viable offspring has not been obtained without genetic manipulation from parthenogenetic embryonic stem cells(pESCs)derived from parthenogenetic embryos,presumably attributable to their aberrant imprinting.We show that an unlimited number of oocytes can be derived from pESCs and produce healthy offspring.Moreover,normal expression of imprinted genes is found in the germ cells and the mice.pESCs exhibited imprinting consistent with exclusively maternal lineage,and higher X-chromosome activation compared to female ESCs derived from the same mouse genetic background.pESCs differentiated into primordial germ cell-like cells(PGCLCs)and formed oocytes following in vivo transplantation into kidney capsule that produced fertile pups and reconstituted ovarian endocrine function.The transcriptome and methylation of imprinted and X-linked genes in pESC-PGCLCs closely resembled those of in vivo produced PGCs,consistent with efficient reprogramming of methylation and genomic imprinting.These results demonstrate that amplification of germ cells through parthenogenesis faithfully maintains maternal imprinting,offering a promising route for deriving functional oocytes and having potential in rebuilding ovarian endocrine function.展开更多
Dear Editor,Identification of oogonia stem cells would have great potentials in infertility treatment and fertility preservation.Here we tested whether Fragilis/lfitm3 can identify oogonia stem cells in fetal mouse ov...Dear Editor,Identification of oogonia stem cells would have great potentials in infertility treatment and fertility preservation.Here we tested whether Fragilis/lfitm3 can identify oogonia stem cells in fetal mouse ovaries and their molecular features,if it can,and whether the oogonia stem cells marked by Fragilis can be found in the postnatal ovaries.展开更多
基金Supported by Scientific and Technological Research Programme of Chongqing Municipal Education Commission,China(No.KJ130320)。
文摘Objective To investigate the mechanistic basis for the anti-proliferation and anti-invasion effect of tumor necrosis factor-related apoptosis-induced ligand(TRAIL)and celastrol combination treatment(TCCT)in glioblastoma cells.Methods Cell counting kit-8 was used to detect the effects of different concentrations of celastrol(0-16µmol/L)and TRAIL(0-500 ng/mL)on the cell viability of glioblastoma cells.U87 cells were randomly divided into 4 groups,namely control,TRAIL(TRAIL 100 ng/mL),Cel(celastrol 0.5µmol/L)and TCCT(TRAIL 100 ng/mL+celastrol 0.5µmol/L).Cell proliferation,migration,and invasion were detected by colony formation,wound healing,and Transwell assays,respectively.Quantitative reverse transcription polymerase chain reaction and Western blotting were performed to assess the levels of epithelial-mesenchymal transition(EMT)markers(zona occludens,N-cadherin,vimentin,zinc finger E-box-binding homeobox,Slug,and β-catenin).Wnt pathway was activated by lithium chloride(LiCl,20 mol/L)and the mechanism for action of TCCT was explored.Results Celastrol and TRAIL synergistically inhibited the proliferation,migration,invasion,and EMT of U87 cells(P<0.01).TCCT up-regulated the expression of GSK-3β and down-regulated the expression of β-catenin and its associated proteins(P<0.05 or P<0.01),including c-Myc,Cyclin-D1,and matrix metalloproteinase(MMP)-2.In addition,LiCl,an activator of the Wnt signaling pathway,restored the inhibitory effects of TCCT on the expression of β-catenin and its downstream genes,as well as the migration and invasion of glioblastoma cells(P<0.05 or P<0.01).Conclusions Celastrol and TRAIL can synergistically suppress glioblastoma cell migration,invasion,and EMT,potentially through inhibition of Wnt/β-catenin pathway.This underlies a novel mechanism of action for TCCT as an effective therapy for glioblastoma.
基金This research was supported by the Ministry of Science and Technology Grant （2001CB510106）；Science and Technology Plan of Beijing Municipal Government （H020220050290）；National Natural Science Foundation of China Awards for 0utstanding Young Scientists （30125022）；for Creative Research Groups （30421004）；Bill ＆ Melinda Gates Foundation Grant （37871） to H Deng.
文摘为人的胚胎的茎(ES ) 的自强和区别的能力细胞为对待类型 Idiabetes mellitus 为胰腺的贝它细胞的产生使他们成为潜在的来源。这里，我们报导一最新发展了并且有效方法，在aserum免费的系统执行了，区分进生产胰岛素的 cells.Activin A 的导致的人的 ES 房间它在起始的阶段被使用从人的 EScells 导致权威的内胚叶区别，是由权威的内胚叶标记 Sox17 和 Brachyury.Further 的表示检测了， all-trans retinoic 酸( RA )被用来支持胰腺的区别，由早胰腺的抄写因素 pdx1 和 hlxb9 的表示显示了。在成熟 inDMEM/F12 以后有 bFGF 和菸碱的没有浆液的媒介，区分的房间表示了小岛特定的标记象 C 肽，胰岛素，胰高血糖素和 glut2 那样。百分比 ofC-peptide-positive 房间超过了 15% 。由这些房间的胰岛素和 C 肽的分泌物在葡萄糖层次对应于变化。当移植了进肾的囊时， ofStreptozotocin (STZ ) 对待裸体老鼠，这些区分的人的 ES 房间熬过并且维持贝它房间标记基因的表示包括 C 肽， pdx1， glucokinase， nkx6.1， IAPP， pax6and Tcf1。百分之三十只移植裸体老鼠展出了 stableeuglycemia 的明显的恢复；并且改正的显型被支撑超过六个星期。我们的新方法为学习人的胰开发的机制提供一个有希望的试管内区别模特儿并且说明为类型 Idiabetes mellitus 的处理使用人的 ES 房间的潜力。
基金supported by the National Key Research and Development Program of China,No.2017YFA0104304(to NG)the National Natural Science Foundation of China,Nos.81571213(to BW),81800583(to YYX),81601539(to DM)+2 种基金the Nanjing Medical Science and Technique Development Foundation of China,Nos.QRX17006(to BW),QRX17057(to DM)the Key Project Supported by Medical Science and Technology Development Foundation,Nanjing Department of Health and the Nanjing Medical Science and Innovation Platform of China,No.ZDX16005(to BW)Chongqing Yuzhong District Science and Technology Commission Project of China,No.20140112(to YYC).
文摘Collagen scaffolds possess a three-dimensional porous structure that provides sufficient space for cell growth and proliferation,the passage of nutrients and oxygen,and the discharge of metabolites.In this study,a porous collagen scaffold with axially-aligned luminal conduits was prepared.In vitro biocompatibility analysis of the collagen scaffold revealed that it enhances the activity of neural stem cells and promotes cell extension,without affecting cell differentiation.The collagen scaffold loaded with neural stem cells improved the hindlimb motor function in the rat model of T8 complete transection and promoted nerve regeneration.The collagen scaffold was completely degraded in vivo within 5 weeks of implantation,exhibiting good biodegradability.Rectal temperature,C-reactive protein expression and CD68 staining demonstrated that rats with spinal cord injury that underwent implantation of the collagen scaffold had no notable inflammatory reaction.These findings suggest that this novel collagen scaffold is a good carrier for neural stem cell transplantation,thereby enhancing spinal cord repair following injury.This study was approved by the Animal Ethics Committee of Nanjing Drum Tower Hospital(the Affiliated Hospital of Nanjing University Medical School),China(approval No.2019AE02005)on June 15,2019.
基金supported by the College of Agriculture and Life Sciences,Cornell University, Ithaca, NY. USAsupport from the United States Agency for International Development (USAID) through the award of the Norman Borlaug Leadership Enhancement in Agriculture Program (LEAP)Fellowship to Moses Okpekuresearch grant from International Foundation for Science, Stockholm to Moses Okpeku
文摘Background: Sheep is important in the socio-economic lives of people around the world. It is estimated that more than half of our once common livestock breeds are now endangered. Since genetic characterization of Nigerian sheep is still lacking, we analyzed ten morphological traits on 402 animals and 15 microsatellite DNA markers in 384 animals of the 4 Nigerian sheep breeds to better understand genetic diversity for breeding management and germplasm conservation. Results: Morphological traits of Uda and Balami were significantly (P < 0.05) higher than Yankasa, which were both higher than West African Dwarf (WAD) sheep. Stepwise discriminant analysis showed tail length, rump height, chest girth, ear length and chest depth as the most discriminating variables for classification. Mahalanobis distances show the least differentiation between Uda and Balami and the largest between WAD and Balami sheep. While 93.3% of WAD sheep were correctly assigned to their source genetic group, 63.9% of Yankasa, 61.2% of Balami and 45.2% of Uda were classified correctly by nearest neighbour discriminant analysis. The overall high Polymorphism Information Content (PIC) of all microsatellite markers ranged from 0.751 to 0.927 supporting their use in genetic characterization. Expected heterozygosity was high for all loci (0.783 to 0.93). Mean heterozygote deficiency across all populations (0.171 to 0.534) possibly indicate significant inbreeding (P < 0.05). Mean values for FST , FIT and FIS statistics across all loci were 0.088, 0.394 and 0.336 respectively. Yankasa and Balami are the most closely related breeds (DA = 0.184) while WAD and Balami are the farthest apart breeds (DA = 0.665), which is coincident with distance based on morphological analysis and population structure assessed by STRUCTURE. Conclusions: These results suggest that within-breed genetic variation in Nigerian sheep is higher than between-breeds and may be a valuable tool for genetic improvement and conservation. The higher genetic variability in Yankasa suggests the presence of unique ancestral alleles reflecting the presence of certain functional genes which may result in better adaptability in more agro-ecological zones of Nigeria. These genetic characteristics are potentially useful in planning improvement and conservation strategies in Nigerian indigenous sheep.
文摘In order to explain the direction,speed and specificity of cell signaling a dual pathway hypothesis is proposed.In this hypothesis the physical pathway is coupled to the biochemical pathway.As an example,the propagation of a mechanical wave along the cytoskeleton components is discussed.
文摘Dermatophytes were earlier reported to respond well to anti-fungal agents;however, an upsurge in resistance with the high cost of these agents increased the use of medicinal plants for treatment. This study investigated the sensitivity pattern of dermatophytes to oral anti-fungal drugs and aqueous leaf extract of the plant, <em>Acacia nilotica</em>. The extract was tested against seven strains of dermatophytes <em>Arthroderma otae</em>, <em>Trichophyton interdigitale</em>, <em>Trichophyton mentagrophyte</em>, <em>Microsporum ferrugineum</em>, <em>Arthroderma vespertilii</em>, <em>Arthroderma quadrifidum</em>, and <em>Arthroderma multifidum</em>, previously isolated from diabetic patients. The minimum inhibitory and fungicidal concentrations of the plant extracts and the standard antifungal agents were evaluated using modifications of the broth macro dilution method of the National Committee for Clinical Laboratory Standards M38-A2 protocol. There was a significant difference in the Minimum Inhibitory concentrations (MIC) of the dermatophytes to the three antifungal drugs tested (p < 0.001). The dermatophytes were mostly susceptible to itraconazole followed by Nystatin. All the dermatophytes tested were resistant to griseofulvin. <em>Acacia nilotica</em> had an inhibitory effect on all the dermatophytes tested, and showed anti-fungal activity in a dose-dependent relationship between 0.625 - 1.25 mg/ml. Though the inhibitions of the dermatophytes were significantly higher with the standard anti-fungal drugs as compared to the plant extract (p < 0.001);however, the dermatophyte, <em>Arthroderma quadrifidum</em>, which was resistant to all the anti-fungal drugs, had the highest inhibition with <em>A. nilotica</em>. Some circulating dermatophyte strains in Nigeria are griseofulvin and/or itraconazole resistant which may influence the spread of infection and <em>A. nilotica</em> aqueous leaf extract showed a strong anti-dermatophytic activity.
文摘<strong>Background:</strong> Cisplatin, a chemotherapeutic agent, is widely used in the treatment of malignant tumors. Nephrotoxicity, especially acute kidney injury (AKI), is the most common and severe adverse reaction of cisplatin. Resveratrol and ginsenoside Rg1, two natural products, have been found to have renal protective effects. However, the effects and the mechanisms in cisplatin-induced AKI need further investigation. <strong>Methods:</strong> The mouse models of cisplatin-induced AKI and several treatment groups were established. Male C57BL/6 mice were divided into five groups: saline control group, cisplatin injury group, resveratrol treatment group, Rg1 treatment group, resveratrol and Rg1 combined treatment group. Serological analysis of serum urea nitrogen was aimed to reflect the function of kidney, and histological analysis of renal tissue sections was aimed to assess the damage of proximal convoluted tubules. The expression levels of autophagy-related proteins Beclin 1 and LC3 were detected by western blotting and qRT-PCR respectively. <strong>Results:</strong> The renal function was improved and renal damage was alleviated in Rg1 and resveratrol alone or combined treatment groups compared with the cisplatin injury group. For the mechanism, treatment with Rg1 and resveratrol alone or in combination decreased the expressions of Beclin 1 both at protein and mRNA levels, decreased LC3II/I protein levels, indicating that autophagy was inhibited by treatment with Rg1 and resveratrol alone or in combination. <strong>Conclusion:</strong> Resveratrol and Rg1 alleviated the kidney damage caused by cisplatin, and reduced autophagy was involved in the renoprotective effects of resveratrol and Rg1 against cisplatin-induced AKI. This study may provide new evidence to alleviate cisplatin-induced AKI.
基金supported by the National Natural Science Foundation of China(No.82103175)the Natural Science Foundation of Shanxi Province,China(No.201901D111432,20210302123316,202103021224379).
文摘Esophageal squamous cell cancer(EScC)is one of the malignant tumors with high morbidity and mortality all over the world.^(1) In recent years,combined chemotherapy has gradually been the effective treatment method for EscC patients.Therefore,it is imperative to explore potential therapeutic targets for the treatment of EsCC.We previously reported a high-frequency amplification of pyrimidine metabolic pathway-related genes in EsCC tissues.
基金was supported by the grants from the Education Department of Liaoning Province(No.LFW201701)Liaoning Provincial Key R&D Project(No.2020JH2/10300114)Key Laboratory of Shenyang Science and Technology Bureau(No.18-007-0-02)。
文摘Since the outbreak of the novel corona virus disease 2019(COVID-19)at the end of 2019,specific antiviral drugs have been lacking.A Chinese patent medicine Toujiequwen granules has been promoted in the treatment of COVID-19.The present study was designed to reveal the molecular mechanism of Toujiequwen granules against COVID-19.A network pharmacological method was applied to screen the main active ingredients of Toujiequwen granules.Network analysis of 149 active ingredients and 330 drug targets showed the most active ingredient interacting with many drug targets is quercetin.Drug targets most ffected by the active ingredients were PTGS2,PTGS1,and DPP4.Drug target disease enrichment analysis showed drug targets were significantly enriched in cardiovascular diseases and digestive tract diseases.An"active ingredient-target-disease"network showed that 57 active ingredients from Toujiequwen granules interacted with 15 key targets of COVID-19.There were 53 ingredients that could act on DPP4,suggesting that DPP4 may become a potential new key target for the treatment of COVID-19.GO analysis results showed that key targets were mainly enriched in the cellular response to lipopolysaccharide,cytokine activity and other functions.KEGG analysis showed they were mainly concentrated in viral protein interaction with cytokine and cytokine receptors and endocrine resistance pathway.The evidence suggests that Toujiequwen granules might play an effective role by improving the symptoms of underlying diseases in patients with COVID-19 and multi-target interventions against mutiple signaling pathways related to the pathogenesis of COVID-19.
基金Supported by the National Natural Science Foundation of China (No.81300463No.81130051)+2 种基金Fundamental Research Funds for Non-profit Public Scientific Research Institutions of Chongqing (No.2012CSTC-jbby01704)Natural Science Foundation Project of CQ CSTC(No. cstc2013jcyjA 10086)Promotion Program for Young and Middle-aged Teacher in Scientific Research of Basic Medicin College,Chongqing Medical University (No.JC201306)
文摘AIM: To identify disease-causing mutation in a congenital cataract family using enrichment of targeted genes combined with next-generation sequencing.· METHODS: A total of 371 known genes related to inherited eye diseases of the proband was selected and captured, followed by high-throughput sequencing. The sequencing data were analyzed by established bioinformatics pipeline. Validation was performed by Sanger sequencing.·RESULTS: A recurrent heterozygous non-synonymous mutation c.130 G >A(p.V44M) in the GJA3 gene was identified in the proband. The result was confirmed by Sanger sequencing. The mutation showed co-segregation with the disease phenotype in the family but was not detected in unaffected controls.·CONCLUSION: Targeted exome sequencing is a rapid,high-throughput and cost-efficient method for screening known genes and could be applied to the routine gene diagnosis of congenital cataract.
基金financially supported by the National Natural Science Foundation of China(General Program),No.31271494Excellent Talent Support Program of Liaoning Province,No.LJQ2011004
文摘3β-Hydroxysteroid-Δ24 reductase(DHCR24) is a multifunctional enzyme that localizes to the endoplasmic reticulum and has neuroprotective and cholesterol-synthesizing activities. DHCR24 overexpression confers neuroprotection against apoptosis caused by amyloid β deposition. The present study aimed to construct two recombinant adenoviruses driving DHCR24 expression specifically in neurons. Two SYN1 promoter DNA fragments were obtained from human(h) and rat(r). Recombinant Ad-r(h)SYN1-DHCR24 was transfected into AD-293, N2A(mouse neuroblastoma), and MIN6(mouse pancreatic carcinoma) cells. Western blot analysis showed DHCR24 was specially expressed in 293 and N2A cells, but no specific band was found in MIN6 cells. This demonstrates that the recombinant adenoviruses successfully express DHCR24, and no expression is observed in non-neuronal cells. TUNEL assay results showed apoptosis was inhibited in adenovirus-transfected neurons. Detecting reactive oxygen species by immunofluorescence, we found that adenovirus transfection inhibits apoptosis through scavenging excess reactive oxygen species. Our findings show that the recombinant DHCR24 adenoviruses induce neuron-specific DHCR24 expression, and thereby lay the foundation for further studies on DHCR24 gene therapy for Alzheimer's disease.
文摘In view of increasing lead pollution(Pb^(2+)) of coastal waters, the compensatory abilities of holothurians need to be assessed. The goal of the work is to clarify the functional and phenotypical differences between two types of phagocytes(P1 and P2) in Eupentacta fraudatrix exposed to Pb(NO_3)_2. It has been shown that 2 mg L^(-1) lead exposure for 48 h increases the number of P2 phagocytes as compared to P1 cells, does not significantly affect cell viability in both P1 and P2 phagocyte fractions, and significantly enhances chromatin condensation in P2 but not in P1 phagocytes. A lead concentration of 4 mg L^(-1) increases the number of P1 phagocytes compared to that of P2 type, and does not change cell viability and chromatin condensation in P1 phagocytes. In the P2 type, it decreases cell viability and does not influence the level of apoptosis. The protection against lead-induced apoptosis is apparently mediated by the activities of antioxidant enzymes, especially glutathione S-transferase. The differences in labeling cell surface receptors of P1 and P2 phagocytes by plant lectins also indicate the specific phenotypic properties of these cells. The results clarify the potential and GSH-dependent mechanisms of immune adaptation in holothurians that have been shortly exposed to lead at concentrations close to the maximum environmentally relevant level in coastal waters. Additionally, P1 and P2 phagocytes are first shown to have different functions and phenotypes during the response to lead, which indicates the complexity of the phagocytic system in holothurians and contributes to understanding the immunity evolution.
文摘OBJECTIVE This study was conducted to explore the effect of Rg3 on inhibition of proliferation and induction of apoptosis in bladder cancer cells. METHODS The EJ bladder cancer cell line was treated with Rg3 at various concentrations. Cell proliferation was measured by the MTT assay. Morphological changes in the cells were observed by fluorescent staining using Hoechst 33258. The cell cycle and apoptotic rate were analyzed by flow cytometry (FCM) and the expression of caspase-3 in cells was detected by immunocytochemistry. DMA ladder analysis was conducted by agarose gel electrophoresis. RESULTS Rg3 inhibited proliferation of EJ cells in a concentration-dependent manner, resulting in an IC50 for Rg3 at 48 h of 125.5μg/ml. When treated with 150μg/ml of Rg3 for 24 h and 48 h, the cells showed apoptotic morphological characteristics including condensed chromatin, nuclear fragmentation, apoptotic bodies and bright fluorescent granules as well as a higher caspase-3 expression. The FCM assay indicated that Rg3 altered the cell cycle and induced apoptosis of the EJ cells, when treated for 24 h and 48 h with 75μg/ml of Rg3 as well as for 48 h with 150μg/ml. The percentages of cells in the S phase and the G2/M transition were increased, whereas the percentages of cells in the G0-G1 transition were decreased. The apoptotic rates were increased from (1.05±0.17)% in the control group cells to (8.41±0.98)%,(18.57±2.20)% and (33.98±1.64)% respectively. Significant changes in the DNA ladders, showed that the effects of Rg3 were displayed in a dose and time dependent manner. CONCLUSION The results suggest that Ginsenoside Rg3 exerts an inhibitory effect on proliferation of EJ cells by inducing apoptosis.
文摘Indiscriminate handling and disposal of industrial effluents into the environment represents one of the major sources of environmental pollution which invariably affect plants, animals and humans. This study assessed heavy metal concentration in soils and plants around industries in Agbara industrial estate, Ogun State, Nigeria. Soil and plant samples were collected from four industries and analyzed for lead (Pb), cadmium (Cd), copper (Cu), chromium (Cr) and nickel (Ni). The pH, organic matter content and cation exchange capacity of the soil samples, as well as bioaccumulation factor (BAF) and translocation factor (TF) of the plant samples were examined. The heavy metal concentration order of the soil and plant samples was Pb ?1, 50 mg kg?1, 10 mg kg?1 and 50 mg kg?1 respectively) while Cd was above WHO tolerance limit (3 mg kg?1). Also, Pb, Cd, Cu, and Cr in most plant samples were above WHO tolerance limits (10 mg kg?1, 0.30 mg kg?1, 10 mg kg?1 and 1.5 mg kg?1 respectively). Statistical differences (P Cyperus iria, Alternanthera sessilis, C. esculentus, A. brasiliana, and Megathyrsus maximus are probable accumulators of heavy metals.
文摘Pigmentation plays important adaptation and physiological efficiency roles in animals. In the sequence of a 648 bp fragment representing intron 1, exon 2, and part of intron 2 of the MLPH mammalian pigmentation gene, we identified a novel g.469C> G mutation in intron 2, and genotyped it in 266 Nigerian goats using PCR-RFLP analysis. The C allele had frequencies of 0.9625, 0.9804 and 0.97405 in West African Dwarf (WAD),Sahel(SH) and Red Sokoto (RS) breeds, respectively. The G allele was the highest in WAD (0.0375), followed by RS (0.02595), and then SH (0.0196). Overall low FIS and FST and high Nm values demonstrate little differentiation within and among the goat breeds at this intronic locus. This g.469C> G polymorphism in MLPH gene is the first in any goat breed and also first in Nigerian goats. Our results suggest that this intronic SNP locus is maintained at Hardy-Weinberg equilibrium (P < 0.05) and the lack of association of this SNP with coat color may indicate its neutrality in goats.
文摘Tumor is a serious disease that threatens human health and has a high mortality. Chemotherapy is the most commonly used treatment, but it has a lot of side effects due to its toxicity. It has been found that ginsenosides exert an effective antitumor role. Ginsenosides are a class of triterpenoid saponins primarily found in the plant genus Panax. Many monomer components are studied, the most often investigated are Rg3, and Rh2, etc. Reports have shown that ginsenosides can inhibit tumor cells by suppressing proliferation and metastasis, and promoting apoptosis. In addition, ginsenosides can enhance sensitivity to conventional chemotherapeutic drugs. In this review, the recent articles about anti-tumor of ginsenosides were reviewed to promote the further development of anti-tumor therapy.
基金This work was supported by the Hunan Province Science and Technology Innovation Plan Project(grant number 2021NK1004)the Changsha Natural Science Foundation(grant number kq2208157)China Agriculture Research System of MOF and MAR(grant number CARS_12).The authors thank Wuhan Benagen Tech Solutions Co.,Ltd for assistance with bioinformatics analysis.
文摘Allopolyploid oilseed rape(Brassica napus)is an important oil crop and vegetable.However,the latest version of its reference genome,with collapsed duplications,gaps,and other issues,prevents comprehensive genomic analysis.Herein,we report a gap-free assembly of the rapeseed cv.Xiang5A genome using a combination of ONT(Oxford Nanopore Technologies)ultra-long reads,PacBio high-fidelity reads,and Hi-C datasets.It includes gap-free assemblies of all 19 chromosomes and telomere-to-telomere assemblies of eight chromosomes.Compared with previously published genomes of B.napus,our gap-free genome,with a contig N50 length of 50.70 Mb,has complete assemblies of 9 of 19 chromosomes without manual intervention,and greatly improves contiguity and completeness,thereby representing the highest quality genome assembly to date.Our results revealed that B.napus Xiang5A underwent nearly complete triplication and allotetraploidy relative to Arabidopsis thaliana.Using the gap-free assembly,we found that 917 flowering-related genes were affected by structural variation,including BnaA03.VERNALIZATION INSENSITIVE 3 and BnaC04.HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENES 1.These genes may play crucial roles in regulating flowering time and facilitating the adaptation of Xiang5A in the Yangtze River Basin of China.This reference genome provides a valuable genetic resource for rapeseed functional genomic studies and breeding.
基金supported by the National Natural Science Foundation of China(No.81802793 and 82103465)Natural Science Foundation of Shanxi Province(China)(No.201801D221419)+4 种基金Youth Foundation of First Hospital Affiliated with Shanxi Medical University(China)(No.YQ161701)Science Research Start-up Fund for Doctor of Shanxi Medical University(China)(No.XD1801)Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi(China)(STIPNo.2021-185)Fund of Shanxi"1331 Project"Key Subjects Construction(China).
文摘Circular RNAs (circRNAs) are a special class of single-stranded RNA molecules with covalently closed loops widely expressed in eukaryotic organisms. CircRNAs have long been considered to play important roles in various physiological and pathological processes as non-coding RNAs. However, circRNAs have recently garnered considerable attention due to their ability to be translated into peptides/proteins via internal ribosome entry site- or N6-methyladenosine-mediated pathways or rolling translation mechanisms. Furthermore, dysregulation of translatable circRNAs and their encoded proteins has been associated with developing and progressing diseases such as cancer. This review aims to summarize the driving mechanisms of circRNA translation and the available strategies in circRNA translation research. The main focus is on the emerging biological functions of translatable circRNAs, their regulatory mechanisms, and potential clinical applications in human diseases to provide new perspectives on disease diagnosis, prognosis, and targeted therapy.
基金This work was supported by China National Key R&D Program(2018YFC1003004,2018YFA0107002)the National Natural Science Foundation of China(31430052,91749129)as well as the Stanley H.Kaplan Research Fund at NYU School of Medicine.
文摘Parthenogenetic embryos,created by activation and diploidization of oocytes,arrest at mid-gestation for defective paternal imprints,which impair placental development.Also,viable offspring has not been obtained without genetic manipulation from parthenogenetic embryonic stem cells(pESCs)derived from parthenogenetic embryos,presumably attributable to their aberrant imprinting.We show that an unlimited number of oocytes can be derived from pESCs and produce healthy offspring.Moreover,normal expression of imprinted genes is found in the germ cells and the mice.pESCs exhibited imprinting consistent with exclusively maternal lineage,and higher X-chromosome activation compared to female ESCs derived from the same mouse genetic background.pESCs differentiated into primordial germ cell-like cells(PGCLCs)and formed oocytes following in vivo transplantation into kidney capsule that produced fertile pups and reconstituted ovarian endocrine function.The transcriptome and methylation of imprinted and X-linked genes in pESC-PGCLCs closely resembled those of in vivo produced PGCs,consistent with efficient reprogramming of methylation and genomic imprinting.These results demonstrate that amplification of germ cells through parthenogenesis faithfully maintains maternal imprinting,offering a promising route for deriving functional oocytes and having potential in rebuilding ovarian endocrine function.
文摘Dear Editor,Identification of oogonia stem cells would have great potentials in infertility treatment and fertility preservation.Here we tested whether Fragilis/lfitm3 can identify oogonia stem cells in fetal mouse ovaries and their molecular features,if it can,and whether the oogonia stem cells marked by Fragilis can be found in the postnatal ovaries.
