scholarly journals A paradoxical role for sestrin 2 protein in tumor suppression and tumorigenesis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Junsheng Qu ◽  
Moyi Luo ◽  
Jingwen Zhang ◽  
Fang Han ◽  
Ningning Hou ◽  
...  

AbstractSestrin 2, a highly conserved stress-induced protein, participates in the pathological processes of metabolic and age-related diseases. This p53-inducible protein also regulates cell growth and metabolism, which is closely related to malignant tumorigenesis. Sestrin 2 was reported to regulate various cellular processes, such as tumor cell proliferation, invasion and metastasis, apoptosis, anoikis resistance, and drug resistance. Although sestrin 2 is associated with colorectal, lung, liver, and other cancers, sestrin 2 expression varies among different types of cancer, and the effects and mechanisms of action of this protein are also different. Sestrin 2 was considered a tumor suppressor gene in most studies, whereas conflicting reports considered sestrin 2 an oncogene. Thus, this review aims to examine the literature regarding sestrin 2 in various cancers, summarize its roles in suppression and tumorigenesis, discuss potential mechanisms in the regulation of cancer, and provide a basis for follow-up research and potential cancer treatment development.

2019 ◽  
Vol 25 (14) ◽  
pp. 1696-1716 ◽  
Author(s):  
Ida Frugaard Stroem ◽  
Helene Flood Aakvaag ◽  
Tore Wentzel-Larsen

This study investigates the relationship between the characteristics of different types of childhood violence and adult victimization using two waves of data from a community telephone survey (T1) and a follow-up survey, including 505 cases and 506 controls, aged 17-35 years (T2). The logistic regression analyses showed that exposure to childhood abuse, regardless of type, was associated with adult victimization. Exposure to multiple types of abuse, victimization both in childhood and in young adulthood, and recency of abuse increased these odds. Our findings emphasize the importance of assessing multiple forms of violence when studying revictimization. Practitioners working with children and young adults should be attentive to the number of victimization types experienced and recent victimization to prevent further abuse.


2021 ◽  
pp. 112067212110057
Author(s):  
Pierre Gascon ◽  
Prithvi Ramtohul ◽  
Charles Delaporte ◽  
Sébastien Kerever ◽  
Danièle Denis ◽  
...  

Purpose: To report the visual and anatomic outcomes in treatment-naïve neovascular age-related macular degeneration (nAMD) patients treated with aflibercept under a standardized Treat and Extend (T&E) protocol for up to 3 years of follow-up in “real-life” practice. Methods: This retrospective, observational, multicenter study included patients with treatment-naïve nAMD and at least 12 months of follow-up. T&E regimen adjustment was initiated after loading phase. At each visit best-corrected visual acuity (BCVA) and optical coherence tomography parameters were performed. Results: One hundred and thirty-six eyes of 115patients had at least 1 year of follow-up with 114 and 82 eyes completing at least 2 and 3 years of follow-up, respectively (mean follow-up duration: 2.7 ± 1.3 years). Mean age was 78.6 ± 8.6 years old and 52% were women. Mean BCVA increased from 60.6 ± 18.7 letters at diagnosis to 66.9 ± 16.2 letters at 1 year (+6.3 letters, p = 0.003) and remained stable throughout the follow-up period (63.1 ± 20.3 letters (+2.5, p = 0.1) and 64.0 ± 20.1 letters (+3.4, p = 0.27) at 2 and 3 years, respectively). The mean central retinal thickness decreased significantly from 358.2 ± 87.9 µm at baseline to 302 ± 71.7 µm at 12 months and maintained stable after 36 months of follow-up (297.1 ± 76 µm, p < 0.0001). Mean number of injections was 6.6 ± 2.2, 4.8 ± 1.9, and 5.6 ± 1.7 at 1, 2, and 3 years, respectively. Mean cumulative number of 16.4 ± 5.6 injections after 3 years. Mean treatment interval was 6.8 ± 2.5 weeks at 1 year. Eight-week and 12-week treatment interval were achieved in 59.5% and 19.1%, 65.8%, and 36.8% and 69.5% and 41.5% at 1, 2, and 3 years, respectively. Conclusions: Our study demonstrated that intravitreal injections of aflibercept initiated under a standardized T&E for patients with treatment-naïve nAMD allow for significant visual improvement at 12 months, which was maintained over a 3-year follow-up period.


Medicina ◽  
2021 ◽  
Vol 57 (7) ◽  
pp. 660
Author(s):  
Csilla-Andrea Eötvös ◽  
Roxana-Daiana Lazar ◽  
Iulia-Georgiana Zehan ◽  
Erna-Brigitta Lévay-Hail ◽  
Giorgia Pastiu ◽  
...  

Among the different types, immunoglobulin light chain (AL) cardiac amyloidosis is associated with the highest morbidity and mortality. The outcome, however, is significantly better when an early diagnosis is made and treatment initiated promptly. We present a case of cardiac amyloidosis with left ventricular hypertrophy criteria on the electrocardiogram. After 9 months of follow-up, the patient developed low voltage in the limb leads, while still maintaining the Cornell criteria for left ventricular hypertrophy as well. The relative apical sparing by the disease process, as well as decreased cancellation of the opposing left ventricular walls could be responsible for this phenomenon. The discordance between the voltage in the frontal leads and precordial leads, when present in conjunction with other findings, may be helpful in raising the clinical suspicion of cardiac amyloidosis.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M De Carlo ◽  
R Liga ◽  
G.M Migaleddu ◽  
M Scatturin ◽  
C Spaccarotella ◽  
...  

Abstract Background Most patients undergoing transcatheter aortic valve implantation (TAVI) develop silent cerebral ischemic lesions (SCIL) detectable at magnetic resonance imaging (MRI). The natural history and clinical relevance of SCIL are not well established. We aimed to assess the characteristics, predictors, evolution, and neurocognitive effects of SCIL. Methods Cerebral MRI was performed within 7 days before TAVI to assess baseline status and age-related white matter changes (ARWMC) score. MRI was repeated postoperatively to assess the occurrence, location, number and dimensions of SCIL. Patients developing SCIL underwent a third MRI at 3–5 months follow-up. A neurocognitive evaluation was performed before TAVI, at discharge and at 3-month follow-up. Results Of the 117 patients enrolled, 96 underwent a postprocedural MRI; SCIL were observed in 76% of patients, distributed in all vascular territories, with a median number of 2 lesions, median diameter 4.5 mm, and median total volume 140 mm3. Independent predictors of SCIL occurrence were a higher baseline ARWMC score and the use of self-expanding or mechanically-expanded bioprostheses. Among 47 patients who underwent follow-up MRI, only 26.7% of postprocedural SCIL evolved into a gliotic scar. SCIL occurrence was associated with a more pronounced transient neurocognitive decline early after TAVI and with a lower recovery at follow-up. Conclusions SCIL occur in the vast majority of patients undergoing TAVR and are predicted by a more diffuse white matter damage at baseline and by the use of non-balloon-expandable prostheses. Although most SCIL disappear within months, their occurrence has a limited but significant impact on neurocognitive function. Figure 1 Funding Acknowledgement Type of funding source: Private company. Main funding source(s): unrestricted grants from Edwards Lifesciences SA, Nyon, Switzerland, and from Medtronic Italia SpA, Milan, Italy


Biology ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 163
Author(s):  
Swapnil Gupta ◽  
Panpan You ◽  
Tanima SenGupta ◽  
Hilde Nilsen ◽  
Kulbhushan Sharma

Genomic integrity is maintained by DNA repair and the DNA damage response (DDR). Defects in certain DNA repair genes give rise to many rare progressive neurodegenerative diseases (NDDs), such as ocular motor ataxia, Huntington disease (HD), and spinocerebellar ataxias (SCA). Dysregulation or dysfunction of DDR is also proposed to contribute to more common NDDs, such as Parkinson’s disease (PD), Alzheimer’s disease (AD), and Amyotrophic Lateral Sclerosis (ALS). Here, we present mechanisms that link DDR with neurodegeneration in rare NDDs caused by defects in the DDR and discuss the relevance for more common age-related neurodegenerative diseases. Moreover, we highlight recent insight into the crosstalk between the DDR and other cellular processes known to be disturbed during NDDs. We compare the strengths and limitations of established model systems to model human NDDs, ranging from C. elegans and mouse models towards advanced stem cell-based 3D models.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Giuseppe Querques ◽  
Riccardo Sacconi ◽  
Francesco Gelormini ◽  
Enrico Borrelli ◽  
Francesco Prascina ◽  
...  

AbstractThere is a lack of treatment aimed at the regression of reticular pseudodrusen (RPD) secondary to age-related macular degeneration (AMD). The aim of this prospective, pilot study is to evaluate the safety and short-term efficacy of subthreshold laser treatment (SLT) in patients affected by RPD secondary to dry AMD (dAMD). Twenty eyes of 20 patients (mean age 78.4 ± 6.8 years) with RPD secondary to dAMD were prospectively enrolled. All patients were treated in an extrafoveal area of 1.27 mm2 using end-point management yellow subthreshold laser and followed for 3 months. Best-corrected visual acuity was 0.140 ± 0.09 LogMAR at the baseline and no changes were observed during the follow-up (p = 0.232). No significant worsening was disclosed before and after the treatment analyzing the macular sensitivity of the treated area (p = 0.152). No topical and/or systemic side effects were disclosed during the 3-month follow-up. The distribution among the RPD stages changed after the treatment (p < 0.001). In detail, in the treated area, we observed a significant increase in the number of Stage 1 RPD during the follow-up (p = 0.002), associated with a significant decrease of Stage 3 RPD (p = 0.020). Outer nuclear layer (ONL) thickness analysis showed a significant increase after the treatment associated with RPD regression (p = 0.001). End-point management SLT appears a safe treatment for RPD secondary to dAMD, showing short-term safety outcomes. Our results suggest that SLT could be effective in inducing a RPD regression in terms of RPD stage and ONL thickening.


The Knee ◽  
2021 ◽  
Vol 31 ◽  
pp. 11-21
Author(s):  
Simo Miettinen ◽  
Henrik Nyländen ◽  
Jussi Jalkanen ◽  
Hannu Miettinen ◽  
Heikki Kröger ◽  
...  

Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 2047
Author(s):  
Bénédicte M. J. Merle ◽  
Audrey Cougnard-Grégoire ◽  
Jean-François Korobelnik ◽  
Wolfgang Schalch ◽  
Stéphane Etheve ◽  
...  

Lutein and zeaxanthin may lower the risk of age-related macular degeneration (AMD). We evaluated the associations of plasma lutein and zeaxanthin with the incidence of advanced AMD in the Alienor study (Antioxydants Lipides Essentiels Nutrition et Maladies Oculaires). Alienor study is a prospective population-based cohort of 963 residents of Bordeaux, France, who were 73 years or older at baseline (2006–2008). The present study included 609 participants with complete ophthalmologic and plasma carotenoids data. Examinations were performed every two years over an eight-year period (2006 to 2017). Plasma lutein and zeaxanthin were determined at baseline from fasting blood samples using high-performance liquid chromatography. Cox proportional hazard models were used to assess associations between plasma lutein, zeaxanthin, and their (total cholesterol (TC) + triglycerides (TG)) ratios with AMD. Among the 609 included participants, 54 developed advanced incident AMD during a median follow-up time of 7.6 years (range 0.7 to 10.4). Participants with higher plasma lutein had a reduced risk for incident advanced AMD in the fully adjusted model (HR = 0.63 per 1-SD increase (95% CI, 0.41–0.97), p = 0.03). A similar association was observed using the lutein/(TC + TG) ratio (HR = 0.59 (95% CI, 0.39–0.90), p = 0.01). No associations were evidenced for other carotenoids. Higher plasma lutein was associated with a 37% reduced risk of incident advanced AMD.


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