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Yujie Hu

Publications and source records attributed to Yujie Hu.

5 recordsLinked to original sources
PubMed2026

A bi-directional Mendelian randomization study of sarcopenia-related traits and renal function.

The association between sarcopenia and renal function has been reported in observational studies; however, the directionality and potential causal nature of these associations remain uncertain. We assessed whether genetically predicted sarcopenia-related traits are associated with renal function and vice versa using bidirectional Mendelian randomization (MR). We conducted a bidirectional two-sample MR analysis using publicly available European-ancestry GWAS summary statistics for appendicular lean mass (ALM), hand-grip strength (left and right), and walking pace, and for renal function (cystatin C-based estimated glomerular filtration rate [eGFRcystatin C] and urinary albumin excretion [UAE]). Causal estimates were primarily obtained using inverse-variance weighted (IVW) models, complemented by sensitivity analyses (MR-Egger intercept, weighted median/mode, MR-PRESSO, Radial MR, and leave-one-out). In forward MR, genetically predicted walking pace was positively associated with eGFRcystatin C. Genetically predicted ALM and grip strength (right and left) were inversely associated with UAE. In reverse MR, genetically predicted UAE was inversely associated with ALM and right-hand grip strength. Estimates were broadly consistent across sensitivity analyses, and outlier-robust analyses (MR-PRESSO/Radial MR) yielded similar results. These findings provide genetic evidence consistent with bidirectional relationships between sarcopenia-related traits and renal function (particularly UAE), under standard MR assumptions. Given potential limitations (e.g., heterogeneity, pleiotropy, and possible sample overlap), the results should be interpreted cautiously and complemented by other lines of evidence.

Humans↗
PubMed2006

Caldesmon transgene expression disrupts focal adhesions in HTM cells and increases outflow facility in organ-cultured human and monkey anterior segments.

Cytoskeleton modulating compounds have been shown to lower intraocular pressure (IOP) and increase outflow facility. Caldesmon is one protein that is involved in the regulation of actin stress fiber formation. The effects of rat non-muscle caldesmon (Cald) gene over-expression on focal adhesions in human trabecular meshwork (HTM) cells and on outflow facility in organ-cultured human and monkey anterior segments were determined. Treatment of HTM cells with adenovirus-delivered caldesmon (AdCaldGFP) resulted in characteristic changes in the actin cytoskeleton and matrix adhesions within 24-48 hr post-transduction. Stress fibers gradually disappeared and novel actin structures were formed (see manuscript by Grosheva et al., this issue). In cells with disrupted stress fibers, vinculin-containing focal adhesions were also disrupted. In organ-cultured anterior segments, baseline outflow facility (microl min-1 mmHg-1) for all anterior segments averaged (mean+/-sem): human, 0.19+/-0.03 (n=12); monkey, 0.36+/-0.02 (n=19). In human anterior segments, transduction with 10(7) plaque forming units of AdGFPCald increased outflow facility by 43+/-21% (p<or=0.11, n=6) at 66 hr compared to baseline and corrected for the changes in outflow facility of the contralateral vehicle treated segment. Using the same time point, i.e. 2-3 days after injection, outflow facility in monkey anterior segments, transduced with 1.5x10(7) plaque forming units of AdGFPCald was increased by 35+/-18%, p<0.2, n=10 compared to baseline and corrected for the change in outflow facility in the contralateral AdGFP treated segment. Combining human (66 hr) and monkey (2-3 days) data, outflow facility was increased by 38+/-13%, p<0.02, n=16. Additional analysis of maximum responses in monkey anterior segments from 1 to 6 days after transduction showed outflow facility was increased by 66+/-18%, p<0.01, n=10. Caldesmon over-expression, which relaxes cultured HTM cells and disrupts their actin cytoskeleton and cell-matrix adhesions, also appears to increase outflow facility in organ-cultured human and monkey anterior segments. This suggests that over-expression of the caldesmon gene in the TM may be an effective approach for the gene therapy of glaucoma.

Actins↗
PubMed2006

Monkey organ-cultured anterior segments: technique and response to H-7.

In the intact primate eye in vivo, it may be difficult to determine whether an outflow facility response is due to direct effects on the trabecular meshwork or indirectly via an effect on ciliary muscle tone unless complicated surgical ciliary muscle disinsertion or isotope accumulation procedures are used. We established a monkey anterior segment organ culture system modeled after the human anterior segment organ culture system and determined its characteristics and response to H-7, an agent shown to increase trabecular outflow in vivo and in other organ culture systems. Outflow facility studies conducted using the monkey organ-cultured anterior segment system showed that: baseline values were comparable to those measured in vivo; washout occurred with time; the two-level constant pressure perfusion technique gave results comparable to the constant rate technique; species differences were found comparing baseline outflow facility and intraocular pressure in rhesus and cynomolgus monkey organ-cultured anterior segments; there was no effect of age on outflow facility in either species by one-way ANOVA; anterior segment exchange perfusion increased outflow facility if measured within 1 hr of the exchange; the magnitude of the response to H-7 was comparable to those reported in vivo and in other in vitro systems. The onset of the response to H-7 was delayed in most cases (day after H-7 exchange), compared to in vivo monkey studies (onset 6-9 min) and in vitro human and porcine organ culture systems (within 1 hr). Also the duration of the response (2-3 days from the onset) was longer than that found for in vitro human studies (1 day). Thus, the monkey organ-cultured anterior segment system can be used to determine the effects of pharmacological and biological agents on trabecular outflow.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed2005

The effect of C3 transgene expression on actin and cellular adhesions in cultured human trabecular meshwork cells and on outflow facility in organ cultured monkey eyes.

PURPOSE: To determine the effects of adenovirus-delivered exoenzyme C3 transferase (C3) gene expression on cultured human trabecular meshwork (HTM) cells and on outflow facility in organ cultured monkey anterior segments. METHODS: An adenoviral (Ad) vector expressing both C3 and green fluorescent protein (GFP) was used to transduce cultured HTM cells. Changes in cell morphology and the organization of actin, vinculin, and beta-catenin were assessed using immunofluorescence. Cultured monkey eye anterior segments were used to test the effects of AdC3GFP on outflow facility. RESULTS: Treatment of HTM cells with AdC3GFP resulted in dose-dependent morphological changes 3 or 4 days post-transduction. The AdC3GFP-transduced cells were either partially retracted, rounded, or very elongated compared to non-transduced cells. Compared to AdGFP-transduced cells, AdC3GFP-transduced cells demonstrated disrupted actin cytoskeleton, reduced vinculin-positive focal adhesions, and loss of beta-catenin staining. Cells transduced with AdGFP did not round up or retract. In organ culture studies, outflow facility was increased by 90+/-21% (n=15, p<0.001) in AdC3GFP-transduced eyes compared to baseline and corrected for AdGFP-transduced control eye washout on days 3-6 after transduction. CONCLUSIONS: C3 transduction is effective in disrupting actin filaments, cytoskeleton, and cellular adhesions in HTM cells and in increasing outflow facility in organ cultured monkey anterior segments, suggesting that expressing the C3 gene in the trabecular meshwork may be an effective approach for glaucoma therapy.

ADP Ribose Transferases↗