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Biomedical subjects

Ningli Wang

Publications and source records attributed to Ningli Wang.

10 recordsLinked to original sources

Base editing for precision therapeutics.

Base editing (BE), the precise installation of single-nucleotide changes in DNA or RNA without inducing double-strand breaks, holds substantial therapeutic promise for correcting single-nucleotide variants, which constitute more than half of the known pathogenic genetic variants. Recent advances have improved base editor specificity, efficiency, and delivery, enabling clinically oriented procedures. Clinically, BE has shown early success or strong translational promise in sickle cell disease, β-thalassemia, leukemia (via CAR T and epitope engineering), hypercholesterolemia (PCSK9 and ANGPTL3), alpha-1-antitrypsin deficiency, and glycogen storage disease type Ia. Key remaining challenges include bystander editing within the activity window, residual off-target DNA and RNA editing, delivery constraints (payload size, tissue targeting, and redosing limits), immunogenicity, and the need for durable long-term safety evidence across relevant cell types and disease contexts. Continued technological refinements, careful preclinical validation, and rigorous clinical assessment will be essential to fully realize BE's transformative potential in precision medicine.

Humans↗

Unilateral optic nerve transection up-regulate Hsp70 protein expression in lateral geniculate nucleus of rats.

Studies have demonstrated that optic nerve transection results in apoptotic cell death of retinal ganglion cells (RGCs) and neurons within lateral geniculate nucleus (LGN). Heat shock protein (Hsp) 70 was reported to be involved in protecting cells from injury under various pathological conditions in vivo and in vitro. To determine the involvement of Hsp70 in protecting neurons within LGN against damage or loss induced by optic nerve injuries, we observed the changes in protein expression and distribution of Hsp70 in LGN at days 1, 3, 7, 14 and 28 after unilateral optic nerve transection in the left eye of Sprague-Dawley rats by using Western blot analysis and immunohistochemical staining. We found that the levels of Hsp70 protein expression increased significantly (p < 0.05, n = 6 for each group) in both right and left LGN of rats following left optic nerve transection 1-7 days. The maximum of Hsp70 expression reached at day 3. However, Hsp70 protein expression levels in both right and left LGN returned to control levels at 14 and 28 days after left optic nerve lesion. In addition, the increased Hsp70 expression, which mainly localized in the intergeniculate leaflet of LGN, was also observed by immunostaining in right LGN at the end of day 3 after the lesion. These results suggest that increased expression of Hsp70 may be involved in protecting neurons within LGN against damage or loss induced by left optic nerve transection at early stage.

Animals↗

[Effect of RU38486 on fibronectin expression in cultured human trabecular cells].

OBJECTIVE: To study the effect of RU38486 on fibronectin expression in human trabecular cells (HTCs) in vitro. METHODS: The trabecular specimens from human donors were primarily cultured and subcultured. Cultured cells were observed by light and electron microscopes. Fibronectin (FN), laminin (LN) and neuron-specific enolase (NSE) in extracellular matrix (ECM) of the cells were immunohistochemically stained with LSAB method. The quantities of FN [optical density (A) means] affected by different concentrations of dexamethasone (Dex) and RU38486 were measured through indirect immunochemical method associated with computer image analysis. RESULTS: According to the growing characteristics and morphological features, the cultured cells were identified as HTCs. Comparison of A means of FN induced by Dex and RU38486 was 10(-6) mol/L dex (12 days) > 10(-7) mol/L Dex (12 d) > 10(-7) mol/L Dex (5 d) > Control group = 10(-7) mol/L Dex (5 d) + 10(-8) mol/L RU38486 (7 d). CONCLUSION: Dex can stimulate HTCs in vitro to secrete more FN. Bit RU38486 can reverse this high level of FN expression induced by Dex on receptor level. The efficacy of RU 38486 [glucocorticoid receptor (GR)-antagonist] in reducing intraocular pressure in vivo should be confirmed by further studies.

Dexamethasone↗

[Alteration of lateral geniculate body cells after partial injury].

OBJECTIVE: To investigate the damage of the cells of the lateral geniculate bodies (LGB) of Sprague-Dawley (SD) rats after partial optic nerve injury. METHODS: The optic nerve was pressed by a forceps (40 g) for 30 seconds to set up the animal model with optic nerve injury. LGB was chopped in serial coronal slices (10 microm thickness) by a cryomicrotome. The apoptosis of LGB cells was detected with terminal deoxynucleotidyl transferase (TDT)-mediated dUTP nick end-labeling (TUNEL) technique after one week. After retrograde labeling with Granular Blue (GB) through injecting GB into optic center, the average density of the LGB cells was counted under the fluorescent microscope. Using monoclonal rabbit anti-rat neurofilament (NF) antibody, the neurons of LGB were detected by immunochemistry stains, and the standard avidin-biotin complex immunoperoxidase technique was used for immunostaining. RESULTS: The results of TUNEL analysis showed that the mechanism of the LGB cells pathogenesis was apoptosis. The LGB cells appeared clear striation in the control group, and the cells in experimental group decreased obviously after immunohistrochemical staining. The average density of LGB cells was (5 172 +/- 248) cells/mm(2) in control group, and (4 144 +/- 61) cells/mm(2) in experimental group. CONCLUSION: After partial optic nerve injury, the LGB cells are obviously damaged, which may be related to apoptosis of LGB cells.

Animals↗

[Analysis of intra-operative and early post-operative complications and safety in non-penetrating trabecular surgery].

OBJECTIVE: To evaluate the safety, effectiveness and complications of non-penetrating trabecular surgery (NPTS). METHODS A total of 168 patients ( 258 eyes) of primary open angle glaucoma were divided into 2 groups randomly, and they were matched according to the age, sex and severity of disease. NPTS with reticulated hyaluronic acid implant was taken in one group, and traditional trabeculectomy was taken in the other. Pre-a2operative mean intraocular pressure (IOP) in the NPTS group and trabeculectomy group was (31.85 +/- 4.83) and (32.59 +/- 4.62) mm Hg (1a(c)mm Hg = 0.133 kPa), respectively. The post-operative IOP and complications in these 2 groups were compared. RESULTS: (1) IOP: The mean IOP on post-operative 7th, 14th day, 1st, 3rd and 6th month was (6.67 +/- 2.43), (11.42 +/- 2.89), (12.59 +/- 2.24), (15.45 +/- 1.82), and (17.99 +/- 1.80) mm Hg respectively in the NPTS group, while that in the trabeculectomy group for the same time a(c)series was (4.87 +/- 1.65), (10.48 +/- 2.38), (12.01 +/- 2.83), (15.01 +/- 2.66), an.d (17.48 +/- 2.97) mm Hg respectively. Statistically significant differences between these 2 groups were found on the post-operative 7th day and 14th day (t = 7.03, 2.89; P < 0.000 1, P = 0.004). However, significant difference was not noted for pre-operative and other post-operative IOP in the follow-up (t = 1.28, 1.78, 1.55, 1.60; P = 0.202, 0.077, 0.124, 0.112). (2) Visual acuity: There were no statistical differences of visual acuity between the 2 groups (kappa(2) = 0.135, 0.151, 0.024, 0.076; P = 0.935, 0.927, 0.988, 0.963). (3) COMPLICATIONS: I and II degree shallow anterior chamber was encountered in 57 eyes in the NPTS group, while that in the trabeculectomy group was 70. Twelve eyes with III degree shallow anterior chamber were found exclusively in the trabeculectomy group. Ciliary body or choroidal detachment was found in 66 and 70 eyes respectively in the NPTS and trabeculectomy group. Hypotony was encountered in 5 eyes exclusively in the trabeculectomy group. COMPLICATIONS were found to be statistically different in 2 groups (kappa(2) = 9.95, 15.27, 4.60, 6.19; P < 0.05). Hyphema was found in 2 and 6 eyes respectively in the NPTS and trabeculectomy group. Light anterior uveitis was found in 5 and 9 eyes respectively in the NPTS and trabeculectomy group. Vitreous extrusion was experienced in 1 eye of trabeculectomy group. Some complications (16.2%) related to operative skill were also experienced in the NPTS group. CONCLUSIONS: Over-filtration and surgical injury related complications are significantly reduced in the NPTS group compared to those in the trabeculectomy group. NPTS is safer than traditional trabeculectomy. Mastering surgical skills is required for reducing complications of NPTS.

Female↗

Protection of retinal ganglion cells against glaucomatous neuropathy by neurotrophin-producing, genetically modified neural progenitor cells in a rat model.

OBJECTIVE: To investigate in vivo survival of retinal ganglion cells (RGCs) after partial blockage of optic nerve (ON) axoplasmic flow by sub-retinal space or vitreous cavity injection of brain-derived neural factor (BDNF) produced by genetically modified neural progenitor cells (NPCs). METHODS: Adult Sprague-Dawley (SD) rat RGCs were labeled with granular blue (GB) applied to their main targets in the brain. Seven days later, the left ON was intra-obitally crushed with a 40 g power forceps to partially block ON axoplasmic flow. Animals were randomized to three groups. The left eye of each rat received a sham injection, NPCs injection or an injection of genetically modified neural progenitors producing BDNF (BDNF-NPCs). Seven, 15 and 30 days after ON crush, retinas were examined under a fluorescence microscope. By calculating and comparing the average RGCs densities and RGC apoptosis density, RGC survival was estimated and the neuro-protective effect of transplanted cells was evaluated. RESULTS: Seven, 15 and 30 days after crush, in the intra-vitreous injection group, mean RGC densities had decreased to 1885 +/- 68, 1562 +/- 20, 1380 +/- 7 and 1837 +/- 46, 1561 +/- 58, 1370 +/- 16, respectively with sham injection or neural progenitors injection. However, RGCs density in the groups treated with intra-vitreous injection of BDNF-NPC was 2101 +/- 15, 1809 +/- 19 and 1625 +/- 34. Similar results were found in groups after sub-retinal injection. Higher densities were observed in groups treated with BDNF-NPCs. There were statistically significant differences among groups through nonparametric tests followed by the Mann-Whitely test. RGC apoptosis density in BDNF-NPC at each follow-up time was less than in other groups. CONCLUSIONS: A continuous supply of neurotrophic factors by the injection of genetically modified neural progenitors presents a highly effective approach to counteract optic neuropathy and RGC degeneration after partial ON axoplasmic flow blockage.

Animals↗

Primary angle closure glaucoma in Chinese and Western populations.

OBJECTIVE: To review the major progress in primary angle closure glaucoma (PACG). METHODS: Contents of this article were selected from the original papers or reviews related to primary angle closure glaucoma published in Chinese and foreign journals. A total of 76 articles were selected from several hundred original articles or reviews. The content of selected articles is in accordance with our purpose and the authors are authorized scientists in the study of glaucoma. RESULTS: Primary angle closure glaucoma is the most common type of glaucoma in the Sino-Mongoloid population. PACG in Chinese can be classified into three types depending on the mechanism of angle closure: 1. Multimechanism: 54.8% of Chinese PACG is caused by co-existing factors. The pattern of angle closure appears to mainly be creeping closure. After iridectomy, almost 40% of the cases still manifest a positive response to the darkroom provocative test and progressive synechial closure or recurrent angle closure may occur. Several mechanisms are involved in this form of PACG such as pupillary blocking component, iris crowding component and anterior positioned ciliary body. These factors can coexist in the follow patterns: pupillary blocking and iris crowding coexist; pupillary blocking and anterior positioned ciliary body coexist or three of them co-exist. 2. Pupillary block: (38.1% of Chinese PACG) is caused by iris bombe due to pupillary block with acute or subacute attack. It responds well to iridectomy or laser iridotomy. 3. Non-pupillary blocking: (7.8% of Chinese PACG). They usually have a deeper anterior chamber, and tend to be younger (below 40 years of age). Angle closure in this form of PACG is caused by: iris crowding mechanism or/and anteriorly positioned ciliary body against iris root to angle. It is critical to distinguish multi-mechanism PACG from other types. The initial treatment for this type of PACG is also iridectomy, but after the pupillary block component is eliminated by iridectomy, the residual non-pupillary blocking components should be highlighted by a diagnostic treatment procedure or by a ultrasound biomicroscopy (UBM) provocative test. Finally, the role of UBM in the observation and evaluation of the mechanism of angle closure is discussed and future research directions on PACG in Asians are proposed. CONCLUSION: Chinese eyes have been recognized to be prone to the development of creeping angle closure. There is some direct evidence that creeping angle closure is caused by multiple mechanisms. Further study on this topic is needed.

Asian People↗

[Drug therapy for residual angle-closure glaucoma after laser iridectomy].

OBJECTIVE: To observe and compare the effect of 0.005% latanoprost and 0.5% timolol solutions in the treatment of post-iridectomy residual angle-closure glaucoma. METHODS: Laser peripheral iridectomy was performed and 68 cases (68 eyes) of post-iridectomy residual angle-closure glaucoma were selected and treated with 0.005% latanoprost once at night as the study group and 0.5% timolol twice a day as the control group Intraocular pressure (IOP) was measured before treatment, on day 3, week 1, week 2, week 4, month 2, month 3 and month 6 in the follow-up, and visual acuity, visual field and C/D ratio were monitored. RESULTS: Of 68 patients, 56 (82.4%) complete the 6 month follow-up. The basic IOP for all subjects in two groups before treatment was not statistically different (t = 0.236, P = 0.814). After the treatment for three days, the efficiency in IOP reduction was statistically different between 2 groups with repeated measure ANOVA (F = 287.441, P < 0.001). In each group, the IOP after treatment was statistically different from that at baseline, with t = 14.103, P < 0.001 and t = 10.308, P < 0.001 in the latanoprost and timolol groups respectively. For those patients who finished 6 months' follow-up, the IOP difference between the 2 groups was statistically significant with repeated measure ANOVA (F = 74.259, P < 0.001). The IOP was statistically reduced in both the latanoprost and the timolol groups with F = 148.787, P < 0.001 and F = 54.875, P < 0.001 respectively. At each follow-up time, the IOP in latanoprost group was statistically different from that of the timolol group with t values to be -6.127, -5.930, -6.201, -5.931, -7.412, -6.640 and -6.756 (P < 0.001). The IOP was statistically different from that before treatment in each group with a mean difference to be -7.034 approximately -6.897 in the latanoprost group and -4.704 approximately -5.000 in the timolol group (P < 0.001). The IOP was not statistically different within each group in the follow-up with mean difference of 0.034 approximately 0.138 (P = 0.904 approximately 0.629) in the latanoprost group and a mean difference of 0.037 approximately 0.296 (P = 0.910 approximately 0.366) in the timolol group. The best-corrected visual acuity, visual field and C/D ratio were not significantly changed during follow-up. CONCLUSIONS: 0.005% latanoprost and 0.5% timolol can be used in the drug therapy of post-iridectomy angle-closure glaucoma and the efficiency of 0.005% latanoprost is better than of 0.5% timolol. Drug therapy of post-iridectomy angle-closure glaucoma is a practical strategy.

Adolescent↗

The influence of central corneal thickness and corneal curvature and axial length on the measurement of intraocular pressure.

PURPOSE: To examine the influence of central corneal thickness (CCT), corneal curvature (CC), and axial length (AL) on intraocular pressure (IOP). METHODS: Eighty-one clinically normal eyes were included in our study. The IOP, CCT, CC, AL were measured using a Goldmann applanation tonometer, optical pachymeter, keratometer and A-scan ultrasound biometer respectively in all subjects. RESULTS: A highly significant positive correlation was identified between IOP and CCT. Linear regression analysis suggests that an increase in CCT of 0.010 mm is associated with a 4.946 mmHg increment in IOP. No significant positive correlation was identified between IOP and CC. P values are 0.724 and 0.414 respectively for vertical and horizontal readings. A paradoxically reversed correlation was present between IOP and axial length. CONCLUSION: Corneal thickness is a very important confounding factor in the measurement of intraocular pressure, which warrants further attention in our clinical practice.

Adolescent↗