PTB: Not just a polypyrimidine tract-binding protein.

Polypyrimidine tract-binding protein (PTB), as a member of the heterogeneous nuclear ribonucleoprotein family, functions by rapidly shuttling between the nucleus and the cytoplasm. PTB is involved in the alternative splicing of pre-messenger RNA (mRNA) and almost all steps of mRNA metabolism. PTB regulation is organ-specific; brain- or muscle-specific microRNAs and long noncoding RNAs partially contribute to regulating PTB, thereby modulating many physiological and pathological processes, such as embryonic development, cell development, spermatogenesis, and neuron growth and differentiation. Previous studies have shown that PTB knockout can inhibit tumorigenesis and development. The knockout of PTB in glial cells can be reprogrammed into functional neurons, which shows great promise in the field of nerve regeneration but is controversial.

"Ring on Anastomosis" for Avoidance of Acute Proximal Anastomotic Leak after Open Surgical Repair of Abdominal Aortic Aneurysm.

BACKGROUND: Acute proximal anastomotic leak is among severe complications after open surgical repair (OSR) of abdominal aortic aneurysm. We have proposed an approach of "ring on anastomosis" (ROA) as a technical improvement of conventional OSR to reinforce proximal anastomotic section. METHODS: One hundred and nineteen abdominal aortic aneurysm patients admitted to Xiangya Hospital, Central South University were enrolled. Patients were randomly divided into conventional group (n = 54) and ROA group (n = 65). The ring is prepared by cutting out a 2-cm circle from the graft. Operative time, intraoperative blood loss, perioperative mortality, and retroperitoneal hematoma were recorded. Poisson distribution analysis was used between two groups. All methods were carried out in accordance with Declaration of Helsinki. RESULTS: No obvious difference in operative time or intraoperative blood loss was identified [(205.5 ± 6.535) versus (195.6 ± 6.034) minutes, P > 0.05; (756 ± 98.22) versus (673.1 ± 98.93) ml, P > 0.05, respectively]. Two patients in conventional group (2/54, 3.7%) died while no dead case was reported in ROA group (P = 0.047). Three cases in conventional group experienced retroperitoneal hematoma while none was witnessed in ROA group (P = 0.027). An average of 18 months of follow-up was obtained in all patients, and no proximal anastomotic stenosis was reported. CONCLUSIONS: As a technical improvement of conventional OSR, ROA reinforces aorta graft anastomotic section and diminishes anastomotic leak as well as perioperative death without extra cost of time and money.

p38 MAPK inhibitor SB202190 suppresses ferroptosis in the glutamate-induced retinal excitotoxicity glaucoma model.

JOURNAL/nrgr/04.03/01300535-202410000-00031/figure1/v/2024-02-06T055622Z/r/image-tiff Glutamate excitotoxicity has been shown to play an important role in glaucoma, and glutamate can induce ferroptosis. The p38 mitogen-activated protein kinase (MAPK) pathway inhibitor SB202190 has a potential ability to suppress ferroptosis, and its downstream targets, such as p53, have been shown to be associated with ferroptosis. However, whether ferroptosis also occurs in retinal ganglion cells in response to glutamate excitotoxicity and whether inhibition of ferroptosis reduces the loss of retinal ganglion cells induced by glutamate excitotoxicity remain unclear. This study investigated ferroptosis in a glutamate-induced glaucoma rat model and explored the effects and molecular mechanisms of SB202190 on retinal ganglion cells. A glutamate-induced excitotoxicity model in R28 cells and an N-methyl-D-aspartate-induced glaucoma model in rats were used. In vitro experiments showed that glutamate induced the accumulation of iron and lipid peroxide and morphological changes of mitochondria in R28 cells, and SB202190 inhibited these changes. Glutamate induced the levels of p-p38 MAPK/p38 MAPK and SAT1 and decreased the expression levels of ferritin light chain, SLC7A11, and GPX4. SB202190 inhibited the expression of iron death-related proteins induced by glutamate. In vivo experiments showed that SB202190 attenuated N-methyl-D-aspartate-induced damage to rat retinal ganglion cells and improved visual function. These results suggest that SB202190 can inhibit ferroptosis and protect retinal ganglion cells by regulating ferritin light chain, SAT1, and SLC7A11/Gpx4 pathways and may represent a potential retina protectant.

Ripa-56 protects retinal ganglion cells in glutamate-induced retinal excitotoxic model of glaucoma.

Glaucoma is a prevalent cause of blindness globally, characterized by the progressive degeneration of retinal ganglion cells (RGCs). Among various factors, glutamate excitotoxicity stands out as a significant contributor of RGCs loss in glaucoma. Our study focused on Ripa-56 and its protective effect against NMDA-induced retinal damage in mice, aiming to delve into the potential underlying mechanism. The R28 cells were categorized into four groups: glutamate (Glu), Glu + Ripa-56, Ripa-56 and Control group. After 24 h of treatment, cell death was assessed by PI / Hoechst staining. Mitochondrial membrane potential changes, apoptosis and reactive oxygen species (ROS) production were analyzed using flow cytometry. The alterations in the expression of RIP-1, p-MLKL, Bcl-2, BAX, Caspase-3, Gpx4 and SLC7A11 were examined using western blot analysis. C57BL/6j mice were randomly divided into NMDA, NMDA + Ripa-56, Ripa-56 and control groups. Histological changes in the retina were evaluated using hematoxylin and eosin (H&E) staining. RGCs survival and the protein expression changes of RIP-1, Caspase-3, Bcl-2, Gpx4 and SLC7A11 were observed using immunofluorescence. Ripa-56 exhibited a significant reduction in the levels of RIP-1, p-MLKL, Caspase-3, and BAX induced by glutamate, while promoting the expression of Bcl-2, Gpx-4, and SLC7A1 in the Ripa-56-treated group. In our study, using an NMDA-induced normal tension glaucoma mice model, we employed immunofluorescence and H&E staining to observe that Ripa-56 treatment effectively ameliorated retinal ganglion cell loss, mitigating the decrease in retinal ganglion cell layer and bipolar cell layer thickness caused by NMDA. In this study, we have observed that Ripa-56 possesses remarkable anti- necroptotic, anti-apoptotic and anti-ferroptosis properties. It demonstrates the ability to combat not only glutamate-induced excitotoxicity in R28 cells, but also NMDA-induced retinal excitotoxicity in mice. Therefore, Ripa-56 could be used as a potential retinal protective agent.

Role of epigenetic regulation in glaucoma.

Glaucoma is the world's leading irreversible blinding eye disease. Lowering intraocular pressure is currently the only effective clinical treatment. However, there is a lack of long-acting IOP-lowering drugs, and some patients still experience retinal ganglion cell loss even with good intraocular pressure control. Currently, there is no effective method for neuroprotection and regeneration in clinical practice for glaucoma. In recent years, epigenetics has been widely researched and reported for its role in glaucoma's neuroprotection and regeneration. This article reviews the changes in histone modifications, DNA methylation, non-coding RNA, and m6A methylation in glaucoma, aiming to provide new perspectives for glaucoma management, protection of retinal ganglion cells, and axon regeneration by understanding epigenetic alterations.

Growth of nanostructured Cu3Al alloy films by magnetron sputtering for non-enzymatic glucose-sensing applications.

Enzymatic glucose sensors usually exhibit excellent sensitivity and selectivity but suffer from poor stability due to the negative influence of temperature and humidity on enzyme molecules. As compared to enzymatic glucose sensors, non-enzymatic counterparts are generally more stable but are facing challenges in concurrently improving both sensitivity and selectivity of a trace amount of glucose molecules in physiological samples such as saliva and sweat. Here, a novel non-enzymatic glucose sensor based on nanostructured Cu3Al alloy films has been fabricated by a facile magnetron-sputtering followed by controllable electrochemical etching approach. Since the metal Al is more reductive than Cu, by selectively etching aluminum in the Cu3Al alloys, nanostructured alloy films were obtained with increased surface contact area and electrocatalytic active sites which resulted in enhanced glucose-sensing performance. Thus, non-enzymatic glucose sensors based on nanostructured Cu3Al alloy films not only exhibited a high sensitivity of 1680 µA mM-1 cm-2 but also achieved a reliable selectivity to glucose without interference by other species in physiological samples. Consequently, this study sparked the potential for the development of non-enzymatic biosensors for the continuous monitoring of blood glucose levels with high sensitivity and impressive selectivity for glucose molecules.

Comparison of clinical outcomes between cystotome-assisted prechop phacoemulsification surgery and femtosecond laser-assisted cataract surgery for hard nucleus cataracts.

BACKGROUND/OBJECTIVES: To compare the safety and efficacy of cystotome-assisted prechop phacoemulsification surgery (CAPPS) and femtosecond laser-assisted cataract surgery (FLACS) in patients with hard nucleus cataract. SUBJECTS/METHODS: Ninety-six eyes of 64 patients with grade IV hard nucleus cataract were assigned to 1 of the 2 groups (49 CAPPS and 47 FLACS). Follow-up visits were performed at 1 day, 1 week, 1 month, 3 months, 6 months, and 1 year, and the outcome measures comprised ultrasound power, effective phacoemulsification time (EPT), corrected distance visual acuity (CDVA), endothelial cell density (ECD), corneal endothelium cell loss rate (ECL), central corneal thickness (CCT), and intraoperative and postoperative complications. RESULTS: The ultrasound power and EPT were lower in the CAPPS group (p = 0.03 and <0.0001, respectively). Patients in both groups gained better CDVA postoperatively. The ECD value decreased at each follow-up visit and did not return to the preoperative level; FLACS resulted in greater endothelial cell loss compared to CAPPS. CCT increased immediately after the surgery and decreased thereafter. The mean CCT value returned to the preoperative level 3 months postoperatively in the CAPPS group, while in the FLACS group, CCT value took 6 months to return to the preoperative level. Miosis was more likely to occur in the FLACS group. CONCLUSIONS: Due to its efficacy and cost-effectiveness, CAPPS is worth promoting and applying to clinical work in the future.

Anti-scarring effect of sodium hyaluronate at filtration pathway after filtering surgery in rabbits.

AIM: To investigate the anti-scarring effect of sodium hyaluronate (HA) at filtration pathway after filtering surgery in a rabbit model. METHODS: Fifteen healthy adult New Zealand white rabbits were selected for trabeculectomy in both eyes. The right eyes were used as HA group with 0.1 mL HA injected into the anterior chamber at the end of the operation; the left eyes were used with 0.1 mL sodium lactate Ringer's solution (RS) injected into the anterior chamber as RS group. Intraocular pressure (IOP), filtering blebs morphology, inflammatory reaction and complications were observed at the 7, 60, and 90d after surgery. RESULTS: One day after surgery, the IOP of HA and RS groups were 12.75±1.92 and 10.50±1.59 mm Hg (P=0.005). At the 7th day postoperative, the filtering blebs of each group were functional type and TGF-ß expression was significantly difference in both groups (0.10±0.01 vs 0.14±0.02, P=0.024). After 60d of the operation, all filtering blebs were scarring and alpha-smooth muscle actin (α-SMA) expression was significantly difference in both groups (0.40±0.04 vs 0.35±0.02, P=0.032). α-SMA positive cells were mainly distributed in the junction of conjunctiva and sclera and around the blood vessels. The collagen volume fraction (CVF) of HA and RS group was (75.49±7.01)% and (79.93±5.35)% (P=0.044). On the 90th day after the operation, CVF was (82.57±5.19)% and (88.08±1.75)% in HA and RS groups (P=0.036). There was no α-SMA positive cell in HA group, while a few positive cells were observed in RS group (P=0.000). CONCLUSION: HA has effect of anti-scar and anti-inflammation on filtration pathway after filtering surgery within 3mo by inhibiting fibroblast proliferation and collagen deposition.

A comprehensive analysis of FOX family in HCC and experimental evidence to support the oncogenic role of FOXH1.

Hepatocellular carcinoma (HCC) remains the second leading cause of cancer related deaths worldwide. Understanding about the molecular biology of HCC and development of targeted therapies are still the main focuses of this type of disease. Here, by connecting the expression levels of FOX proteins with their associated clinical characteristics using TCGA LIHC dataset, we found that 27/40 FOX proteins were highly expressed in HCC tumors compared to normal liver tissues and their expression levels were tightly associated with HCC tumor stage, tumor grade and overall survival. Our experimental results also confirmed that FOXH1 indeed played an oncogenic role in HCC development by promoting cell growth and cell migration/invasion. Mechanistic dissection demonstrated that FOXH1-induced cell growth and cell migration/invasion relied on mTOR signaling because inhibition of mTOR signaling by rapamycin could attenuate FOXH1-mediated phenotypic alterations of HCC cells. The results from orthotopic mouse model also validated that FOXH1 promoted HA22T tumor growth via triggering mTOR activation. Overall, this study not only comprehensively examines the clinical values of FOX proteins in HCC but also provides experimental evidence to support the role of FOXH1 in HCC development, building rationale to develop more effective therapies to treat HCC patients.

Protective activity of tert-butylhydroquinone against oxidative stress and apoptosis induced by glutamate agonizts in R28 cells and mice retina.

Glutamate excitotoxicity can cause cell damage and apoptosis and play an important role in a variety of retinal diseases. Tertiary-butylhydroquinone (tBHQ) is an approved food-grade phenolic antioxidant with antioxidant activity in a variety of cells and tissues. We observed the protective effect of tBHQ on glutamatergic agonist-induced retina and explored its possible mechanism of action through in vitro cell experiments. The results showed that tBHQ had protective effects on NMDA-induced mouse retinal excitotoxicity and glutamate-induced excitotoxicity in rat retinal precursor cells (R28 cells). tBHQ reversed glutamate-induced apoptosis, production of intracellular reactive oxygen species, and reduction of mitochondrial membrane potential. Western blot analysis showed that tBHQ could increase the expression of procaspase-3, Bcl-2, AIF precursor, CAT, SOD2, Nrf2, NQO1, HO-1 and NF-κB in glutamate-treated cells, and decrease the expression of AIF cleavage products. Furthermore, we discovered that tBHQ activated müller glial cells. Based on these results, tBHQ may have antioxidant and anti-apoptotic properties, thus serving as a potential retinal protective agent. Its anti-oxidative stress effect was attributed to up-regulation of Nrf2, and its anti-apoptotic effect was related to its up-regulation of Bcl-2 expression and inhibition of mitochondria-dependent apoptosis.

Depicting Developing Trend and Core Knowledge of Primary Open-Angle Glaucoma: A Bibliometric and Visualized Analysis.

Objective: The prevalence of glaucoma is rising due to an increasing aging population. Because of its insidious and irreversible nature, glaucoma has gradually become the focus of attention. We assessed primary open angle glaucoma, the most common type of glaucoma, to study its present status, global trend, and state of clinical research. Methods: Publications from 2000 to 2021 in Web of Science database were retrieved and analyzed by bibliometrics. VOSviewer and Citespace were used for analysis. Results: A total of 6,401 publications were included in this review, and we found that the number of publications increased from 139 in 2000 to 563 in 2021. American researchers have published the most papers and had the highest h-index and the most citations, while the Journal of Glaucoma has published the most papers on this topic. Some key researchers, contributing institutions, their partnerships, and scientific masterpieces were identified. The publications we reviewed fall into seven categories: publications on intraocular pressure, normal tension glaucoma, risk factors, the trabecular meshwork, optical coherence tomography, surgery, and mutation. Clear study hotspots were described, which began with epidemiology and transitioned to pathogenesis and diagnosis and then to treatment. Conclusion: Studies on primary open angle glaucoma extend well beyond ophthalmology to biochemistry molecular biology, general internal medicine, pharmacology, pharmacy, science technology, and other areas. Interest, research and publications on primary open angle glaucoma are on the rise.

Androgen receptor (AR) decreases HCC cells migration and invasion via miR-325/ACP5 signaling.

Hepatocellular carcinoma (HCC) is the most 5th commonly diagnosed and 2nd most lethal tumor in the world. The obvious gender advantage of HCC indicates that androgen receptor (AR) may play an important role in the tumor occurrence, develop and metastasis of HCC. Here we found that decreased AR could alter miR-325 to increase ACP5 expression in HCC cells, to increase HCC cells migration and invasion capacities. Mechanism dissection revealed that AR could regulate miR-325 expression through transcriptional regulation and miR-325 might directly target the 3'UTR of ACP5-mRNA to suppress its translation. The in vivo orthotopic xenografts mouse model with oemiR-325 also validated in vitro data. Together, these findings suggest that AR may decrease HCC progression through miR-325/ACP5 signaling and targeting the AR/miR-325/ACP5 signaling may help in the development of the novel therapies to better suppress the HCC progression.

Testicular orphan receptor 4 (TR4) promotes papillary thyroid cancer invasion via activating circ-FNLA/miR-149-5p/MMP9 signaling.

The incidence and mortality of papillary thyroid cancer (PTC) have steadily increased. Although conventional therapies are very effective toward differentiated PTC patients, very limited therapeutic options are applicable to those patients with distant metastases. Therefore, better understanding of the molecular biology of metastatic PTC helps identify novel targets and facilitates the development of new therapies. In this study, we first found that testicular orphan receptor 4 (TR4) was significantly increased in PTC tumors spreading to lymph nodes compared to the paired primary tumors. Experimental evidence suggested that TR4 drove PTC progression via promoting its cell invasion and cell migration. Mechanistically, TR4 transcriptionally regulated the expression level of circ-filamin A (FLNA), which competed with matrix metalloproteinase 9 (MMP9) for microRNA (miR)-149-5p binding and led to an increased protein level of MMP9. Interruption assays with various gene manipulations verified that the TR4/circ-FLNA/miR-149-5p/MMP9 signaling axis played a central role in cell invasion and cell migration of PTC cells. Moreover, a xenografted mouse model also confirmed that the TR4/circ-FLNA signal promoted PTC tumor growth. Overall, our study pinpoints the oncogenic role of TR4 in PTC development, and the targeting of TR4/circ-FLNA/miR-149-5p/MMP9 signaling may be an alternative option for metastatic PTC patients.