MicroRNA-21 (miR-21) is thought to be an oncomir because it promotes cancer cell proliferation, migration, and survival. miR-21 is also expressed in normal cells, but its physiological role is poorly ...understood. Recently, it has been found that miR-21 expression is rapidly induced in rodent hepatocytes during liver regeneration after two-thirds partial hepatectomy (2/3 PH). Here, we investigated the function of miR-21 in regenerating mouse hepatocytes by inhibiting it with an antisense oligonucleotide. To maintain normal hepatocyte viability and function, we antagonized the miR-21 surge induced by 2/3 PH while preserving baseline expression. We found that knockdown of miR-21 impaired progression of hepatocytes into S phase of the cell cycle, mainly through a decrease in levels of cyclin D1 protein, but not Ccnd1 mRNA. Mechanistically, we discovered that increased miR-21 expression facilitated cyclin D1 translation in the early phase of liver regeneration by relieving Akt1/mTOR complex 1 signaling (and thus eIF-4F-mediated translation initiation) from suppression by Rhob. Our findings reveal that miR-21 enables rapid hepatocyte proliferation during liver regeneration by accelerating cyclin D1 translation.
In order to assess the relative contribution and the interactions of the plantar cutaneous and muscle proprioceptive feedback
in controlling human erect posture, single or combined vibratory stimuli ...were applied to the forefoot areas and to the tendons
of the tibialis anterior muscles of nine standing subjects using various vibration frequency patterns (ranging from 20 to
80 Hz).
The variations in the centre of foot pressure, ankle angle and the EMG activities of the soleus and tibialis anterior muscles
of each subject were recorded and analysed.
Separate stimulation of the plantar forefoot zones or the tibialis anterior muscles always resulted in whole-body tilts oppositely
directed backwards and forwards, respectively, the amplitude of which was proportional to the vibration frequency. EMG activity
of ankle muscles also varied according to the direction of the postural responses. However, the same vibration frequency did
not elicit equivalent postural responses: in the low frequency range, tactile stimulation induced stronger postural effects
than proprioceptive stimulation, and the converse was the case for the higher frequency range.
Under sensory conflict conditions, i.e. foot sole-flexor ankle muscle co-stimulation, the direction of the body tilts also
varied according to the difference and the absolute levels of the vibration frequencies. In all cases, the resulting postural
shifts always corresponded to the theoretical sum of the isolated effects observed upon vibrating each of these two sensory
channels.
We proposed that tactile and proprioceptive information from the foot soles and flexor ankle muscles might be co-processed
following a vector addition mode to subserve the maintenance of erect stance in a complementary way.
MicroRNAs (miRNAs) constitute a new class of regulators of gene expression. Among other actions, miRNAs have been shown to control cell proliferation in development and cancer. However, whether ...miRNAs regulate hepatocyte proliferation during liver regeneration is unknown. We addressed this question by performing 2/3 partial hepatectomy (2/3 PH) on mice with hepatocyte‐specific inactivation of DiGeorge syndrome critical region gene 8 (DGCR8), an essential component of the miRNA processing pathway. Hepatocytes of these mice were miRNA‐deficient and exhibited a delay in cell cycle progression involving the G1 to S phase transition. Examination of livers of wildtype mice after 2/3 PH revealed differential expression of a subset of miRNAs, notably an induction of miR‐21 and repression of miR‐378. We further discovered that miR‐21 directly inhibits Btg2, a cell cycle inhibitor that prevents activation of forkhead box M1 (FoxM1), which is essential for DNA synthesis in hepatocytes after 2/3 PH. In addition, we found that miR‐378 directly inhibits ornithine decarboxylase (Odc1), which is known to promote DNA synthesis in hepatocytes after 2/3 PH. Conclusion: Our results show that miRNAs are critical regulators of hepatocyte proliferation during liver regeneration. Because these miRNAs and target gene interactions are conserved, our findings may also be relevant to human liver regeneration. (HEPATOLOGY 2010)
This study aims to identify the cerebral networks involved in the integrative processing of somesthetic inputs for kinesthetic purposes. In particular, we investigated how muscle proprioceptive and ...tactile messages can result in a unified percept of one's own body movements. We stimulated either separately or conjointly these two sensory channels in order to evoke kinesthetic illusions of a clockwise rotation of 10 subjects’ right hand in an fMRI environment.
Results first show that, whether induced by a tactile or a proprioceptive stimulation, the kinesthetic illusion was accompanied by the activation of a very similar cerebral network including cortical and subcortical sensorimotor areas, which are also classically found in passive or imagined movement tasks.
In addition, the strongest kinesthetic illusions occurred under the congruent proprio-tactile co-stimulation condition. They were specifically associated to brain area activations distinct from those evidenced under the unimodal stimulations: the inferior parietal lobule, the superior temporal sulcus, the insula-claustrum region, and the cerebellum.
These findings support the hypothesis that heteromodal areas may subserve multisensory integrative mechanisms at cortical and subcortical levels. They also suggest the integrative processing might consist of detection of the spatial coherence between the two kinesthetic messages involving the inferior parietal lobule activity and of a detection of their temporal coincidence via a subcortical relay, the insula structure, usually linked to the relative synchrony of different stimuli. Finally, the involvement of the superior temporal sulcus in the feeling of biological movement and that of the cerebellum in the movement timing control are also discussed.
BACKGROUNDWhilst causes of hepatic artery thrombosis (HAT) after liver transplantation (LT) are multifactorial, early HAT (E-HAT) remains pertinent complication impacting on graft and patient ...survival. Currently there is no screening tool that would identify patients with increased risk of developing E-HAT.
METHODSWe analyzed the native procoagulant state of LT recipients, identified through pretransplant thromboelastographic (TEG) data among other known risk factors, to identify risk factors for E-HAT.
RESULTSThe outcomes of 828 adult patients undergoing LT between 2008 and 2013 were analyzed. Overall, 79 (9.5%) patients experienced HAT, E-HAT was diagnosed in 23, and in the remainder this was “late” HAT. The maximum amplitude (MA) on preoperative TEG was significantly higher in patients diagnosed with E-HAT compared with those who did not (71.2 mm vs 57.9 mm; P < 0.0001). Receiver operating characteristic analysis with the cutoff value for MA of 65 mm or greater returned area under the curve of 0.750 (P < 0.001) predicting E-HAT with a sensitivity of 70%. A total of 7% of patients with an MA of 65 mm or greater went on to develop E-HAT (hazard ratio, 5.28; 95% confidence interval, 2.10-12.29; P < 0.001), whereas only 1.2% patients with an MA less than 65 mm experienced E-HAT.
CONCLUSIONSPreoperative TEG may reliably identify group of recipients at greater risk of developing E-HAT, and intense surveillance and anticoagulation prophylaxis may avoid this serious complication after LT.
Approval of living kidney donors (LKD) with end-stage kidney disease (ESKD) risk factors, such as obesity, has increased. While lifetime ESKD development data are lacking, the study of intermediate ...outcomes such as diabetes is critical for LKD safety. Donation-attributable diabetes risk among persons with obesity remains unknown. The purpose of this study was to evaluate 10-year diabetes-free survival among LKDs and non-donors with obesity. This longitudinal cohort study identified adult, LKDs (1976-2020) from 42 US transplant centers and non-donors from the Coronary Artery Risk Development in Young Adults (1985-1986) and the Atherosclerosis Risk in Communities (1987-1989) studies with body mass index greater than or equal to30 kg/m.sup.2 . LKDs were matched to non-donors on baseline characteristics (age, sex, race, body mass index, systolic and diastolic blood pressure) plus diabetes-specific risk factors (family history of diabetes, impaired fasting glucose, smoking history). Accelerated failure time models were utilized to evaluate 10-year diabetes-free survival. Among 3464 participants, 1119 (32%) were LKDs and 2345 (68%) were non-donors. After matching on baseline characteristics plus diabetes-specific risk factors, 4% (7/165) LKDs and 9% (15/165) non-donors developed diabetes (median follow-up time 8.5 (IQR: 5.6-10.0) and 9.1 (IQR: 5.9-10.0) years, respectively). While not significant, LKDs were estimated to live diabetes-free 2 times longer than non-donors (estimate 1.91; 95% CI: 0.79-4.64, p = 0.15). LKDs with obesity trended toward living longer diabetes-free than non-donors with obesity, suggesting within the decade following donation there was no increased diabetes risk among LKDs. Further work is needed to evaluate donation-attributable diabetes risk long-term.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
High body mass index is a known barrier to access to kidney transplantation in patients with end-stage kidney disease. The extent to which weight and weight changes affect access to transplantation ...among obese candidates differentially by race/ethnicity has received little attention. We included 10 221 obese patients waitlisted for kidney transplantation prior to end-stage kidney disease onset between 1995-2015. We used multinomial logistic regression models to examine the association between race/ethnicity and annualized change in body mass index (defined as stable -2 to 2 kg/m2/year, loss >2 kg/m2/year or gain >2 kg/m2/year). We then used Fine-Gray models to examine the association between weight changes and access to living or deceased donor transplantation by race/ethnicity, accounting for the competing risk of death. Overall, 29% of the cohort lost weight and 7% gained weight; 46% received a transplant. Non-Hispanic blacks had a 24% (95% CI 1.12-1.38) higher odds of weight loss and 22% lower odds of weight gain (95% CI 0.64-0.95) compared with non-Hispanic whites. Hispanics did not differ from whites in their odds of weight loss or weight gain. Overall, weight gain was associated with lower access to transplantation (HR 0.88 95% CI 0.79-0.99) compared with maintenance of stable weight, but weight loss was not associated with better access to transplantation (HR 0.96 95% CI 0.90-1.02), although this relation differed by baseline body mass index and for recipients of living versus deceased donor organs. For example, weight loss was associated with improved access to living donor transplantation (HR 1.24 95% CI 1.07-1.44) in whites but not in blacks or Hispanics. In a cohort of obese patients waitlisted before dialysis, blacks were more likely to lose weight and less likely to gain weight compared with whites. Weight loss was only associated with improved access to living donor transplantation among whites. Further studies are needed to understand the reasons for the observed associations.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
BACKGROUNDBalancing donor and recipient risks in living donor liver transplantation remains an issue of debate. This study assessed the impact of graft selection on outcomes and complications for ...left lobe (LL) versus right lobe (RL) donors and recipients.
METHODSThe medical records of donors and recipients, who underwent living donor liver transplantation at our institution between 2003 and 2015, were reviewed. For donors, we evaluated graft volume, residual liver volume per standard liver volume, length of hospital stay (LOS), complications, and readmissions. For recipients, we looked at graft and patient survival, graft function at postoperative days 7 and 14, graft volume, LOS, biliary complications, Model for End-Stage Liver Disease at transplant, and hepatitis C virus status.
RESULTSAt 5 years posttransplant, there were no significant differences in graft survival for LL recipients (86% 95% confidence interval, 74-93) compared with 82% (95% confidence interval, 69-89) for RL recipients (P = 0.85) or recipient survival (90% vs 84%; P = 0.44). In LL recipients, postoperative days 7 and 14 median international normalized ratio (1.5 and 1.2, respectively) and total bilirubin (4.6 and 2.7) were significantly greater compared with RL recipients (7 and 14 days international normalized ratio 1.2, P < 0.001; 1.1, P = 0.001 and total bilirubin (2.7, P = 0.001; 2.1, P = 0.05)). The LL recipients also had a significantly greater median LOS (14 vs 10, P = 0.008). Median donor LOS was significantly greater for RL donors (7 interquartile range, 7-8 vs 7 interquartile range, 6-7 days, P < 0.001).
CONCLUSIONSThe RL and LL grafts provide comparable long-term outcomes in properly selected donor-recipient pairs and the appropriate use of LL grafts does not impact graft or patient survival at 5 years posttransplant.
PDF
