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1.
Reprod Biol Endocrinol ; 19(1): 99, 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34215278

RESUMO

BACKGROUND: The gonadotropin-releasing hormone (GnRH) antagonist protocol for in vitro fertilization (IVF) often leads to lower pregnancy rates compared to the GnRH agonist protocol. Decreased endometrial receptivity is one reason for the lower success rate, but the mechanisms underlying this phenomenon remain poorly understood. The S100 calcium protein P (S100P) is a biomarker for endometrial receptivity. Both GnRH antagonist and S100P are involved in mediating cell apoptosis. However, the involvement of S100P in reduced endometrial receptivity during the GnRH antagonist protocol remains unclear. METHODS: Endometrial tissue was collected at the time of implantation window from patients undergoing the GnRH agonist (GnRH-a) or GnRH antagonist (GnRH-ant) protocols, as well as from patients on their natural cycles. Endometrial cell apoptosis and expression levels of S100P, HOXA10, Bax, and Bcl-2 were assessed. Ishikawa cells were cultured to evaluate the effects that GnRH antagonist exposure or S100P up- or down- regulation had on apoptosis. RESULTS: Endometrial tissue from patients in the GnRH-ant group showed elevated apoptosis and decreased expression of the anti-apoptotic marker Bcl-2. In addition, endometrial expression of S100P was significantly reduced in the GnRH-ant group, and expression of HOXA10 was lower. Immunofluorescence colocalization analysis revealed that S100P was mainly distributed in the epithelium. In vitro experiments showed that knockdown of S100P in Ishikawa cells induced apoptosis, decreased expression of Bcl-2, while overexpression of S100P caused the opposite effects and decreased expression of Bax. Furthermore, endometrial epithelial cells exposed to GnRH antagonist expressed lower levels of S100P and Bcl-2, increased expression of Bax, and had higher rates of apoptosis. The increased apoptosis induced by GnRH antagonist treatment could be rescued by overexpression of S100P. CONCLUSIONS: We found that GnRH antagonist treatment induced endometrial epithelial cell apoptosis by down-regulating S100P, which was detrimental to endometrial receptivity. These results further define a mechanistic role for S100P in contributing to endometrial apoptosis during GnRH antagonist treatment, and suggest that S100P is a potential clinical target to improve the success of IVF using the GnRH antagonist protocol.

2.
Int J Biol Macromol ; 2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34310990

RESUMO

Traumatic brain injury (TBI) is one of the most devastating nervous injuries. Neural tissue engineering based on stem cells and bioactive scaffold is a promising but challenging approach for neural repair. A cutting-edge system with capability to control the fate of encapsulated stem cells is attractive to enhance neural regeneration after TBI. Herein, an injectable gelatin hydrogel dual-enzymatically cross-linked by horse radish peroxidase (HRP) and choline oxidase (ChOx) was performed as the neural scaffold to load murine bone marrow-derived mesenchymal stem cells (BMSC) for TBI treatment. The results of in vitro cellular experiments showed that low cross-linked gelatin hydrogel could obviously promote cellular viability, neural differentiation, and neurotrophins secretion of the loaded BMSC. In vivo tests on a TBI model of C57BL/6 mouse demonstrated that BMSC-laden gelatin hydrogel implants could significantly reduce the damaged area, ameliorate inflammation, attenuate neuronal apoptosis, facilitate survival and proliferation of endogenous neural cells, and promote the neurological function recovery of TBI mice. All data suggest that establishment of this three-dimensional (3D) gelatin hydrogel stem cell-loaded system is a promising therapeutic strategy for TBI or other neurological rehabilitation.

3.
Carcinogenesis ; 2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34313732

RESUMO

Circular RNA (circRNA) is a large class of covalently closed circular RNA. As a member of competitive endogenous RNA (ceRNA), it participates in the regulation of circRNA-miRNA-mRNA network and plays an important role in the regulation of physiology and pathology. CircRNA is produced by the reverse splicing of exon, intron or both, forming exon or intron circRNA. Studies have shown that circRNA is a ubiquitous molecule, which exceeds the linear mRNA distributed in human cells. Because of its covalent closed-loop structure, circRNA is resistant to RNase R, which is more stable than linear mRNA; circRNA is highly conserved in different species. It was found that circRNA competitively adsorbs miRNA, as a miRNA sponge, to involve in the expression regulation of a variety of genes and plays an important role in tumor development, invasion, metastasis and other processes. These molecules offer new potential opportunities for therapeutic intervention and serve as biomarkers for diagnosis. In this paper, the origin, characteristics and functions of circRNA and its role in tumor development, invasion and metastasis, diagnosis and prognosis are reviewed.

4.
Cell Signal ; 86: 110076, 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34245861

RESUMO

Protein disulfide isomerase (PDI), a principal endoplasmic reticulum resident oxidoreductase chaperone, is known to play a role in malignancies. This study aims to explore the molecular mechanism by which PDI regulates endoplasmic reticulum stress and the apoptosis signaling pathway in colorectal cancer (CRC). We determined the expression of PDI in CRC tissues and adjacent normal tissues. Gain- and loss- of function assays were conducted to evaluate the effects of PDI on oxidative stress, endoplasmic reticulum stress, and apoptosis in CRC cells, as reflected by hydrogen peroxide (H2O2) level and the expression of related proteins. PDI protein expression was upregulated in CRC tissues. Small molecule inhibitor of PDI or PDI knockdown reduced CRC cell viability and induced apoptosis. Overexpression of wild-type PDI augmented the viability of CRC cells and inhibited endoplasmic reticulum stress response and apoptosis. Small molecule inhibitor of PDI or PDI knockdown increased intracellular H2O2 level and activated apoptosis signaling pathway, which could be reversed by wild-type PDI restoration. Moreover, the catalytic active site of C-terminal of PDI was found to be indispensable for the regulatory effects of PDI on H2O2 levels, apoptosis and cell viability in CRC cells. Collectively, PDI inhibits endoplasmic reticulum stress and apoptosis of CRC cells through its oxidoreductase activity, thereby promoting the malignancy of CRC.

5.
Chin Med J (Engl) ; 134(13): 1552-1560, 2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-34250960

RESUMO

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a common public health problem worldwide. Recent studies have reported that socioeconomic status (SES) is related to the incidence of COPD. This study aimed to investigate the association between SES and COPD among adults in Jiangsu province, China, and to determine the possible direct and indirect effects of SES on the morbidity of COPD. METHODS: A cross-sectional study was conducted among adults aged 40 years and above between May and December of 2015 in Jiangsu province, China. Participants were selected using a multistage sampling approach. COPD, the outcome variable, was diagnosed by physicians based on spirometry, respiratory symptoms, and risk factors. Education, occupation, and monthly family average income (FAI) were used to separately indicate SES as the explanatory variable. Mixed-effects logistic regression models were introduced to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for examining the SES-COPD relationship. A pathway analysis was conducted to further explore the pulmonary function impairment of patients with different SES. RESULTS: The mean age of the 2421 participants was 56.63 ±â€Š9.62 years. The prevalence of COPD was 11.8% (95% CI: 10.5%-13.1%) among the overall sample population. After adjustment for age, gender, residence, outdoor and indoor air pollution, body weight status, cigarette smoking, and potential study area-level clustering effects, educational attainment was negatively associated with COPD prevalence in men; white collars were at lower risk (OR: 0.60, 95% CI: 0.43-0.83) of experiencing COPD than blue collars; compared with those within the lower FAI subgroup, participants in the upper (OR: 0.68, 95% CI: 0.49-0.97) tertiles were less likely to experience COPD. Such negative associations between all these three SES indicators and COPD were significant among men only. Education, FAI, and occupation had direct or indirect effects on pulmonary function including post-bronchodilator forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC), FEV1, FVC, and FEV1 percentage of predicted. Education, FAI, and occupation had indirect effects on pulmonary function indices of all participants mainly through smoking status, indoor air pollution, and outdoor air pollution. We also found that occupation could affect post-bronchodilator FEV1/FVC through body mass index. CONCLUSIONS: Education, occupation, and FAI had an adverse relationship with COPD prevalence in Jiangsu province, China. SES has both direct and indirect associations with pulmonary function impairment. SES is of great significance for COPD morbidity. It is important that population-based COPD prevention strategies should be tailored for people with different SES.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Adulto , Idoso , China/epidemiologia , Estudos Transversais , Volume Expiratório Forçado , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Fatores de Risco , Classe Social , Espirometria , Capacidade Vital
6.
Int J Occup Saf Ergon ; : 1-38, 2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-34225576

RESUMO

AbstracHazard recognition is mainly a visual search and cognitive process. Mental representations of hazards may impact mental states of hazard recognition. We assessed the effects of critical indicators of mental presentations of construction hazards on prefrontal cortex activation, a proxy for the mental states of hazard recognition. Students participated in a hazard inspection experiment, with near-infrared spectroscopy (NIRS) used to record prefrontal cortex activation. The effects of critical indicators of the hazards' mental representations on prefrontal activation were analyzed. Results demonstrated that site familiarity, risk tolerance, and safety knowledge have significant effects on medial prefrontal activation for hazards at low visual clutter level. High levels of site familiarity and risk tolerance reduced medial prefrontal activation and saved cognitive resources. Theoretically, the findings supplement the knowledge of safety hazards' mental representations; and practically, the findings guide provision of individual-specific guidance for improving workers' hazard inspection performance.

7.
Plant Genome ; : e20120, 2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34309200

RESUMO

Powdery mildew causes considerable yield losses in common wheat (Triticum aestivum L.) production. Mapping and cloning powdery mildew-resistant quantitative trait loci can benefit stable yield production by facilitating the breeding of resistant varieties. In this study, we used the powdery mildew resistance introgression line 'CH7087' (harboring the resistance gene PmCH7087) and developed a large F2 population and a corresponding F2:3 segregation population containing 2,000 family lines for molecular mapping of PmCH7087. Genetic analysis demonstrated that the resistance phenotype was controlled by a single dominant gene. According to the performance exhibited by the F2:3 lines, 50 resistant lines and 50 susceptible lines without phenotype segregation were chosen for pooling and bulked segregant RNA sequencing (BSR-Seq) analysis. A region spanning 42.77 Mb was identified, and genotyping of an additional 183 F2:3 lines with extreme phenotypes using 20 kompetitive allele-specific polymerase chain reaction (KASP) markers in the BSR-Seq mapping regions confirmed this region and narrowed it to 9.68 Mb, in which 45 genes were identified and annotated. Five of these transcripts harbored nonsynonymous single nucleotide polymorphisms between the two parents, with the transcripts of TraesCS2B01G302800 being involved in signal transduction. Furthermore, TraesCS2B01G302800.2 was annotated as the closest homologue of serine/threonine-protein kinase PBS1, a typical participant in the plant disease immune response, indicating that TraesCS2B01G302800 was the candidate gene of PmCH7087. Our results may facilitate future research attempting to improve powdery mildew resistance in wheat and to identify candidate genes for further verification and gene cloning.

8.
Huan Jing Ke Xue ; 42(8): 3595-3603, 2021 Aug 08.
Artigo em Chinês | MEDLINE | ID: mdl-34309246

RESUMO

In late August 2020, a period of O3 pollution occurred in the main urban area of Chongqing and lasted for approximately 2 weeks (till early September). Ambient air samples, collected using Summa Canisters and DNPH sampling columns at three observation sites in the main urban area, were used to study the composition, photochemical reaction activity, and source apportionment of volatile organic compounds (VOCs) during the period of O3 pollution. The results showed that the mean volume fraction of TVOCs in the main urban area of Chongqing during the observation period was 45.08×10-9, and the components were ranked by volume fraction in the following order:OVOCs, alkanes, halohydrocarbons, alkenes, aromatics, and alkynes. Formaldehyde, ethylene, and acetone made up the higher volume fraction of VOCs, together accounting for more than 30% of TVOCs. OVOCs and alkenes contributed more to · OH loss rate (Li·OH) and ozone formation potential (OFP) and were the key VOCs components for ozone generation. The main active species in the OVOCs component were formaldehyde, acetaldehyde, and acrolein; the main active species in the alkene component were isoprene, ethylene, and n-butene. The ratio of xylene to ethylbenzene in VOCs was low, and they showed a significant correlation, indicating that the VOCs air mass in the main urban area was highly aging and affected by long-distance transmission from other areas. The source apportionment results of the PMF model showed five main sources of VOCs, namely secondary generation (27.67%), vehicle exhaust (26.56%), industrial emission (17.86%), plant (14.51%), and fossil fuel combustion (13.4%).

9.
Int J Mol Sci ; 22(13)2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34281204

RESUMO

Verticillium dahliae is a soil-borne plant pathogenic fungus that causes Verticillium wilt on hundreds of dicotyledonous plant species. V. dahliae is considered an asexually (clonal) reproducing fungus, although both mating type idiomorphs (MAT1-1 and MAT1-2) are present, and is heterothallic. Most of the available information on V. dahliae strains, including their biology, pathology, and genomics comes from studies on isolates with the MAT1-2 idiomorph, and thus little information is available on the MAT1-1 V. dahliae strains in the literature. We therefore evaluated the growth responses of MAT1-1 and MAT1-2 V. dahliae strains to various stimuli. Growth rates and melanin production in response to increased temperature, alkaline pH, light, and H2O2 stress were higher in the MAT1-2 strains than in the MAT1-1 strains. In addition, the MAT1-2 strains showed an enhanced ability to degrade complex polysaccharides, especially starch, pectin, and cellulose. Furthermore, several MAT1-2 strains from both potato and sunflower showed increased virulence on their original hosts, relative to their MAT1-1 counterparts. Thus, compared to MAT1-1 strains, MAT1-2 strains derive their potentially greater fitness from an increased capacity to adapt to their environment and exhibit higher virulence. These competitive advantages might explain the current abundance of MAT1-2 strains relative to MAT1-1 strains in the agricultural and sylvicultural ecosystems, and this study provides the baseline information on the two mating idiomorphs to study sexual reproduction in V. dahliae under natural and laboratory conditions.

10.
Anticancer Drugs ; 2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34261915

RESUMO

Atractylodes is the dry root of atractylodes macrocephala koidz and has been commonly used as a traditional Chinese medicine (TCM). Atractylenolide III, a main component of atractylodes, has displayed significant effects on anti-inflammation and anticancer. However, the effects of atractylenolide III on growth inhibition and apoptosis induction in colon cancer remain unclear. The results showed that atractylenolide III significantly inhibited the cell growth and induce cellular apoptosis in HCT-116 cells in a concentration dependence manner in vitro. Mechanistic studies further showed that atractylenolide III could regulate the Bax/Bcl-2 apoptotic signaling pathway through promoting the expression of proapoptotic related gene/proteins Bax, caspase-9 and caspase-3 but inhibiting the expression of antiapoptotic related gene/protein Bcl-2 in HCT-116 cells. Furthermore, atractylenolide III also significantly inhibited the tumor growth of HCT-116 tumor xenografts bearing in nude mice through inducing apoptosis by upregulation of the expressions of Bax, cleaved caspase-3 and p53 but downregulation of the expressions of Bcl-2 in HCT-116 tumor tissues in vivo. The studies may provide the scientific rationale for the understanding of the anticancer effect of atractylenolide III. Therefore, atractylenolide III may have the potential to be developed as a promising novel anticancer agent for the treatment of colorectal cancer clinically.

11.
Aging (Albany NY) ; 13(undefined)2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34289452

RESUMO

Studies aiming to identify the significance of the carotid artery perivascular fat density are limited. The present study investigated the distribution pattern of pericarotid fat and its association with imaging markers of cerebral small vessel disease (CSVD). In total, 572 subjects who underwent both neck computed tomography angiography and cranial magnetic resonance imaging were analyzed. The pericarotid fat density near the origin of the internal carotid artery (ICA) and imaging markers of CSVD, such as lacunes, white matter hyperintensities (WMHs) and dilated perivascular spaces (PVSs), were assessed. We found that an increased pericarotid fat density was associated with the presence of lacunes and a higher WMH grade in all subjects, but in the patients with acute ischemic stroke, there was a difference only among the WMH grades. There was no significant difference in the pericarotid fat density in different grades of PVSs. The patients with acute ischemic stroke had a significantly higher mean pericarotid fat density than those without stroke. In conclusion, our study provides evidence suggesting that an increased pericarotid fat density is associated with the presence and degree of WMHs and lacunes. Our findings suggested that features that appear to extend beyond the vessel lumen of the ICA may be linked to CSVD.

12.
Chemosphere ; 285: 131450, 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34246095

RESUMO

Soil salinization has severely affected the quality of tillage land in China, and most greenhouse soils in Shanghai suburb suffer from secondary salinization with high salinity levels dominated by Ca2+, Mg2+ and NO3-. In this work, a sandy loam soil (Calcaric Fluvisols) contaminated by the above ions was selected as research object, and the binding conditions and abilities of γ-polyglutamic acid (γ-PGA) to water-soluble Ca2+ and Mg2+ in the soil were examined, and then pot experiments were conducted to remove Ca2+, Mg2+ and NO3- by two halophytes (Sedum aizoon L., Sesbania cannabina Pers.) integrated with γ-PGA application. The results showed that under the conditions of adding 1000 mg L-1γ-PGA (pH 7) and 25 °C, the binding efficiencies of Ca2+ and Mg2+ were 51.59% and 68.03%, respectively. Compared with Sesbania cannabina Pers., Sedum aizoon L. displayed better remediation performance for the soil with γ-PGA application in pot experiments, and the removal efficiencies of Ca2+, Mg2+ and NO3- reached 93.25%, 94.78% and 84.26% after applying 1000 mg L-1γ-PGA for 56 d, respectively. Moreover, γ-PGA application could mitigate salt stress and promote plant growth, and activate antioxidant defense systems. Compared with the control, 1000 mg L-1γ-PGA application significantly increased plant height and fresh weight of Sedum aizoon L., and the removal efficiencies of Ca2+, Mg2+ and NO3- increased by 45.48%, 82.62% and 69.91%, respectively. In the future, more in-depth mechanism of joint effect and field-scale investigation need to be further studied.

13.
Int Immunopharmacol ; 99: 107914, 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34246059

RESUMO

OBJECTIVES: Acute respiratory distress syndrome (ARDS) is characterized by an excessive pulmonary inflammatory response. Pyroptosis is a newly form of programmed inflammatory cell death that is triggered by inflammatory caspases. Studies have shown that Luteolin has powerful anti-inflammation effects through activating the function of regulatory T cells (Tregs). The study aimed at investigating the effects of Luteolin on CLP-induced ALI. METHODS: In our study, we employed the mouse cecal ligation and puncture (CLP) model to explore whether Luteolin contributed to alleviated lung injury in vivo. H&E staining and wet/dry (W/D) weight ratios were used to evaluate the severity of lung injury. The serum and BALF of cytokines were assessed by ELISA. The number of neutrophils in the BALF was counted. Immunohistochemistry of IL-10 and MPO in lung tissue was detected. The ROS level in lung was tested by ROS Assay Kit and expression of Gpx4 in lung tissue was detected by qRT-PCR and Western blotting. The regulatory T cells (Treg) population was analyzed in spleen and Peripheral blood mononuclear cells (PBMCs). The levels of caspase-11 protein, caspase-1 protein, GSDMD protein, IL-1α and IL-1ß protein in the lung tissue was evaluated by Western blotting. RESULTS: We found Luteolin significantly inhibits inflammation and attenuated CLP-induced lung injury in vivo, and the levels of, caspase-11, caspase-1, GSDMD, IL-1α and IL-1ß protein in the lungs of CLP mice decreased significantly after pretreatment with Luteolin. Furthermore, the results showed that Luteolin could increase Treg frequencies and IL-10 levels in serum and BALF of CLP mice. It is noteworthy that depleting Tregs reverse Luteolin ameliorated lung injury, and IL-10 neutralizing antibodies treatment aggravated lung pyroptosis. CONCLUSIONS: Our study illustrated that Luteolin contributed to alleviated lung injury, and attenuated caspase-11-dependent pyroptosis in the lung tissue of the CLP-induced ALI mouse model. The mechanisms could be related to regulating the frequency of Tregs and the levels of Treg derived IL-10. Treg cells were show to produce IL-10 and could alleviating caspase-11-dependent lung pyroptosis.

14.
Mol Biol Evol ; 2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34293158

RESUMO

Insects detect odors using an array of odorant receptors (ORs), which may expand through gene duplication. How and which new functions may evolve among related ORs within a species remain poorly investigated. We addressed this question by functionally characterizing ORs from the Eurasian spruce bark beetle Ips typographus, in which physiological and behavioral responses to pheromones, volatiles from host and non-host trees, and fungal symbionts are well described. In contrast, knowledge of OR function is restricted to two receptors detecting the pheromone compounds (S)-(-)-ipsenol (ItypOR46) and (R)-(-)-ipsdienol (ItypOR49). These receptors belong to an Ips-specific OR-lineage comprising seven ItypORs. To gain insight into the functional evolution of related ORs, we characterized the five remaining ORs in this clade using Xenopus oocytes. Two receptors responded primarily to the host tree monoterpenes (+)-3-carene (ItypOR25) and p-cymene (ItypOR27). Two receptors responded to oxygenated monoterpenoids produced in larger relative amounts by the beetle-associated fungi, with ItypOR23 specific for (+)-trans-(1R, 4S)-4-thujanol, and ItypOR29 responding to (+)-isopinocamphone and similar ketones. ItypOR28 responded to the pheromone E-myrcenol from the competitor Ips duplicatus. Overall, the OR responses match well with those of previously characterized olfactory sensory neuron classes except that neurons detecting E-myrcenol have not been identified. The characterized ORs are under strong purifying selection and demonstrate a shared functional property in that they all primarily respond to monoterpenoids. The variation in functional groups among OR ligands and their diverse ecological origins suggest that neofunctionalization has occurred early in the evolution of this OR-lineage following gene duplication.

15.
Phys Rev Lett ; 127(2): 020502, 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34296925

RESUMO

Simulation of a quantum many-body system at finite temperatures is crucially important but quite challenging. Here we present an experimentally feasible quantum algorithm assisted with continuous variable for simulating quantum systems at finite temperatures. Our algorithm has a time complexity scaling polynomially with the inverse temperature and the desired accuracy. We demonstrate the quantum algorithm by simulating a finite temperature phase diagram of the quantum Ising and Kitaev models. It is found that the important crossover phase diagram of the Kitaev ring can be accurately simulated by a quantum computer with only a few qubits and thus the algorithm may be implementable on current quantum processors. We further propose a protocol with superconducting or trapped ion quantum computers.

16.
Stem Cell Res ; 54: 102448, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34198153

RESUMO

Stargardt disease (STGD1) is the most common inherited retinal dystrophy and ABCA4 c.546--10 T>C is the most commonly reported splice mutation. Here, we generated and characterized two induced pluripotent stem cell (iPSC) lines from a STGD1 patient with compound heterozygous mutations in ABCA4 (c.[5461-10 T > C;5603A > T];[4163 T > C;455G > A]). Episomal vectors containing OCT4, SOX2, KLF4, L-MYC, LIN28 and mp53DD were employed to conduct the reprogramming of patient-derived fibroblasts. Both lines had a normal karyotype, displayed iPSC morphology, expressed pluripotency markers and showed trilineage differentiation potential. These lines can provide a powerful platform for further investigating the pathophysiological consequences of mutations in ABCA4.

17.
Stem Cell Res ; 54: 102439, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34214897

RESUMO

Mutations in ABCA4 gene are causative for autosomal recessive Stargardt disease (STGD1), the most common inherited retinal dystrophy. Here, we report the generation of an induced pluripotent stem cell (iPSC) line from a STGD1 patient carrying biallelic c.[5461-10T>C;5603A>T];[6077T>C] mutations in the ABCA4 gene. Episomes carrying OCT4, SOX2, KLF4, L-MYC, LIN28 and mp53DD were employed for the reprogramming of patient-derived fibroblasts. This iPSC line expressed comparable pluripotency markers as in a commercially available human iPSC line, displayed normal karyotype and potential for trilineage differentiation, and were negative for both reprogramming episomes and mycoplasma test.

18.
Genes (Basel) ; 12(6)2021 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-34198599

RESUMO

PRPF31-associated retinopathy (RP11) is a common form of autosomal dominant retinitis pigmentosa (adRP) that exhibits wide variation in phenotype ranging from non-penetrance to early-onset RP. Herein, we report inter-familial and intra-familial variation in the natural history of RP11 using multimodal imaging and microperimetry. Patients were recruited prospectively. The age of symptom onset, best-corrected visual acuity, microperimetry mean sensitivity (MS), residual ellipsoid zone span and hyperautofluorescent ring area were recorded. Genotyping was performed using targeted next-generation and Sanger sequencing and copy number variant analysis. PRPF31 mutations were found in 14 individuals from seven unrelated families. Four disease patterns were observed: (A) childhood onset with rapid progression (N = 4), (B) adult-onset with rapid progression (N = 4), (C) adult-onset with slow progression (N = 4) and (D) non-penetrance (N = 2). Four different patterns were observed in a family harbouring c.267del; patterns B, C and D were observed in a family with c.772_773delins16 and patterns A, B and C were observed in 3 unrelated individuals with large deletions. Our findings suggest that the RP11 phenotype may be related to the wild-type PRPF31 allele rather than the type of mutation. Further studies that correlate in vitro wild-type PRPF31 allele expression level with the disease patterns are required to investigate this association.

19.
Cancer Lett ; 520: 68-79, 2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34237406

RESUMO

Cellular senescence is a stress response that imposes a growth arrest on cancer and nonmalignant cells during cancer therapy. By secreting a plethora of proinflammatory factors collectively termed the senescence-associated secretory phenotype (SASP), therapy-induced senescent cells can promote tumorigenesis. Moreover, the SASP from senescent cells is also able to drive therapy resistance and mediate many adverse effects of cancer therapy. Because senescent cell production often occurs during cancer therapy, it is important to carefully consider these potential detrimental effects. Senotherapy, which refers to selective removal of senescent cells, has been proposed as a promising adjuvant approach to eliminate the adverse effects of senescent cells. Thus, in this review we summarize in detail the mechanisms by which senescent cells contribute to tumorigenesis and therapeutic resistance. Also, we thoroughly discuss the potential strategies regarding how to effectively circumvent the undesirable effects of therapy-induced senescent cells.

20.
Scientometrics ; : 1-21, 2021 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-34276107

RESUMO

In addition to academic impact, researchers are increasingly concerned with understanding and demonstrating the practical impact of research outside academia. Several frameworks capturing key impact types have been developed based on project experiences, expert opinions, and surveys. This empirical study seeks to contribute to this development by identifying impact types documented in 6,882 case studies submitted to impact evaluation groups in Australia (Engagement and Impact Assessment) and the United Kingdom (Research Excellence Framework). The results of text mining indicate three emerging impact types that extend existing frameworks in terms of the recognition of new opportunities, the length of use, and experience improvement, thereby allowing a variety of researchers, not just those who address popular, short-term, and instrumental issues, to understand and demonstrate their practice impact.

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