Resveratrol protects against diabetic retinal ganglion cell damage by activating the Nrf2 signaling pathway.

Objective: Oxidative stress-induced retinal neurodegenerative changes are among the pathological alterations observed in diabetic retinopathy. Resveratrol (RSV), a polyphenolic compound with diverse pharmacological effects, has shown preventive qualities in several neurodegenerative illnesses, including anti-inflammatory, anti-aging, and antioxidant benefits. However, its therapeutic efficacy in diabetic retinal neurodegeneration has not yet been thoroughly elucidated. Our study aimed to explore the protective mechanisms and therapeutic benefits of RSV on diabetic retinal neurodegeneration alterations. Materials and methods: Using streptozotocin, we created a diabetic mouse model and conducted visual electrophysiological examinations on mice from the normal group, diabetic group, and diabetic group treated with RSV. Retinas were harvested for histological staining. Additionally, primary retinal ganglion cells cultured in high glucose conditions were used to assess malondialdehyde (MDA) levels and superoxide dismutase (SOD) levels upon siRNA-mediated nuclear factor erythroid 2-related factor 2 (Nrf2) interference. Protein levels of Nrf-2, heme oxygenase-1 (HO-1), and transcriptional levels of them were also measured. Results: We demonstrated that RSV significantly improved the retinal morphology and function in the diabetic retinopathy model mice. The treated mice exhibited notable improvements in visual electrophysiology, with a significant reduction in retinal ganglion cell apoptosis. Following RSV treatment, the high glucose-cultured ganglion cells demonstrated a considerable rise in SOD levels and a substantial drop in MOD. Moreover, the protein expression of solute carrier family 7 member 11 (SLC7A11) and Nrf2 significantly increased. RT-PCR and Western blot results indicated a significant attenuation of RSV's therapeutic effects upon Nrf2 inhibition. Conclusion: Our findings suggest that RSV may reduce oxidative stress levels in the retina and inhibit retinal ganglion cell apoptosis via reducing the Nrf2/HO-1 pathway, which lessens the harm that excessive glucose causes to the retina.

Molecule engineering strategy of toll-like receptor 7/8 agonists designed for potentiating immune stimuli activation.

Toll-like receptor 7/8 (TLR-7/8) agonists serve as a promising class of pattern recognition receptors that effectively evoke the innate immune response, making them promising immunomodulatory agents for tumor immunotherapy. However, the uncontrollable administration of TLR-7/8 agonists frequently leads to the occurrence of severe immune-related adverse events (irAEs). Thus, it is imperative to strategically design tumor-microenvironment-associated biomarkers or exogenous stimuli responsive TLR-7/8 agonists in order to accurately evaluate and activate innate immune responses. No comprehensive elucidation has been documented thus far regarding TLR-7/8 immune agonists that are specifically engineered to enhance immune activation. In this feature article, we provide an overview of the advancements in TLR-7/8 agonists, aiming to enhance the comprehension of their mechanisms and promote the clinical progression through nanomedicine strategies. The current challenges and future directions of cancer immunotherapy are also discussed, with the hope that this work will inspire researchers to explore innovative applications for triggering immune responses through TLR-7/8 agonists.

A stable ratiometric fluorescent probe for hypochlorous acid detection and rheumatoid arthritis evaluation.

A ratiometric fluorescent probe (MeO-CNPPV Pdots) based on the principle of fluorescence resonance energy transfer (FRET) was designed for hypochlorous acid (HOCl) and rheumatoid arthritis (RA) detection. The presence of HOCl can block the energy transfer from CNPPV to MeOTPATBT, resulting in a ratio change in the fluorescence of Pdots (I600 nm/I680 nm). This strategy provides a valuable paradigm in early RA evaluation.

Prediction of SMILE surgical cutting formula based on back propagation neural network.

AIM: To predict cutting formula of small incision lenticule extraction (SMILE) surgery and assist clinicians in identifying candidates by deep learning of back propagation (BP) neural network. METHODS: A prediction program was developed by a BP neural network. There were 13 188 pieces of data selected as training validation. Another 840 eye samples from 425 patients were recruited for reverse verification of training results. Precision of prediction by BP neural network and lenticule thickness error between machine learning and the actual lenticule thickness in the patient data were measured. RESULTS: After training 2313 epochs, the predictive SMILE cutting formula BP neural network models performed best. The values of mean squared error and gradient are 0.248 and 4.23, respectively. The scatterplot with linear regression analysis showed that the regression coefficient in all samples is 0.99994. The final error accuracy of the BP neural network is -0.003791±0.4221102 µm. CONCLUSION: With the help of the BP neural network, the program can calculate the lenticule thickness and residual stromal thickness of SMILE surgery accurately. Combined with corneal parameters and refraction of patients, the program can intelligently and conveniently integrate medical information to identify candidates for SMILE surgery.

NAD(P)H: quinone oxidoreductase 1 activatable toll-like receptor 7/8 agonist designed for precise immunotherapy.

An NQO1-responsive precursor, named R848-QPA, has been developed to evoke an anti-tumor immune response. R848-QPA can induce innate immune activation when activated by overexpressed NQO1 in the tumor microenvironment while showing lower activity in NQO1-deprived environments. This strategy provides a new method for the development of tumor-microenvironment-responsive prodrugs for antitumor immunotherapy.

Diosgenin Glucoside Inhibits the Progression of Osteosarcoma MG-63 by Regulating the PI3K/AKT/mTOR Pathway.

BACKGROUND: Trillium tschonoskii Maxim (TTM) exerts antitumor effects on a variety of tumour cells. However, the antitumor mechanism of Diosgenin glucoside (DG) extracted from TTM is not clear. OBJECTIVE: This study aimed to investigate the anti-tumour effects of DG-induced osteosarcoma MG-63 cells and their molecular mechanism. METHODS: CCK-8 assay, HE staining, and flow cytometry were used to detect the effects of DG on the proliferation, apoptosis, and cell cycle of osteosarcoma cells. Wound healing and Transwell invasion assays were used to observe the effect of DG on the migration and invasion of osteosarcoma cells. The anti-tumour mechanism of DG on osteosarcoma cells was investigated by immunohistochemistry, Western blot, and RT-PCR. RESULTS: DG significantly inhibited osteosarcoma cell activity and proliferation, promoted apoptosis and blocked the G2 phase of the cell cycle. Both wound healing and Transwell invasion assays showed that DG inhibited osteosarcoma cell migration and invasion. Immunohistochemical and western blot results showed that DG inhibited the activation of PI3K/AKT/mTOR. We found that DG also significantly downregulated the expression of S6K1 and eIF4F, which might be associated with the inhibition of protein synthesis. CONCLUSION: DG may inhibit proliferation, migration, invasion, and cell cycle G2 phase arrest of osteosarcoma MG-63 cells and promote apoptosis through the PI3K/AKT/mTOR signalling pathway.

Modified suture-assisted canaloplasty in Asians with primary open-angle glaucoma: a prospective study with 12-month follow-up.

BACKGROUND: To evaluate the efficacy and safety of modified suture-assisted canaloplasty in Asians with primary open-angle glaucoma (POAG). METHODS: A prospective, consecutive cases study, evaluating a modified canaloplasty by twisted 6/0 suture was performed on Asian POAG patients. Three modifications of this canaloplasty included opening the Schlemm's canal by viscocanalostomy, circumferential probing by a twisted 6/0 suture and loose suture of the superficial scleral flap. The twisted 6/0 suture was selected as a prober based on characteristical analysis of size and contact measurement as well as chemical composition conducted among 5/0, twisted 6/0 polypropylene sutures and the microcatheter. Success criteria were defined as intraocular pressure (IOP) ≤ 21 mmHg, 18 mmHg, 15 mmHg, and ≥ 20% reduction without (complete success) or with medications (qualified success). Efficacy was assessed by the success rate of circumferential catheterization, IOP values, the success rate of the surgery, the number of IOP-lowering medications, best-corrected vision acuity (BCVA), cup-to-disc ratio (C/D), and mean deviation (MD). Safety was evaluated by adverse events. RESULTS: Forty eyes from 40 consecutive patients were included with a mean follow-up of 14.8 ± 3.0 months. Circumferential catheterization was successfully conducted in 36 eyes (90%). Mean IOP decreased from 26.2 ± 6.9 mmHg to 14.5 ± 2.7 mmHg at 12 months postoperatively. While medication numbers were reduced from 3.2 ± 0.6 to 0.5 ± 0.8 at month 12 (both p < 0.001). Qualified success rate was 97.2% [95% confidence interval (CI) 0.92-1.03], 86.1% (95% CI 0.74-0.98) and 66.7% (95% CI 0.51-0.83) at 12 months with three criteria. BCVA, C/D and MD did not show progression at 1-year follow-up (p > 0.05). Age, baseline IOP, and spherical equivalent negatively influenced the success rate significantly (all p < 0.05). Adverse events included hyphema (30.6%), IOP spike > 25 mmHg (8.3%), and peripheral synechia to the trabecular-Descemet's membrane (2.7%). CONCLUSION: Twisted 6/0 suture can be an ideal material for cannulation. Modified suture-assisted canaloplasty is an effective, safe alternative with a cost-efficient feature for patients with POAG, especially in developing countries. TRIAL REGISTRATION: This trial was registered in the Chinese Clinical Trial Registry ( ChiCTR1900028618 , 29/12/2019).

The Role of Leukocyte-Platelet-Rich Fibrin in Promoting Wound Healing in Diabetic Foot Ulcers.

To explore the effect of leukocyte-platelet-rich fibrin (L-PRF) on promoting wound healing in diabetic foot ulcers. A total of 42 patients with diabetic foot ulcers at our hospital from January 2017 to July 2020 were retrospectively analyzed. A control group and a PRF group were established. The two groups of patients underwent debridement. In the platelet-rich fibrin (PRF) group, autologous L-PRF was used to cover ulcer wounds. One time each week, Vaseline gauze was used to cover the ulcer wounds. In contrast, the control group was treated with the external application of mupirocin ointment and recombinant human epidermal growth factor gel (yeast). Two times each week, the sterile Vaseline gauze was covered with a bandage. Both groups were treated for 5 weeks. The wound recovery of the two groups was observed. During the early stage of treatment (first and second weeks) for diabetic foot ulcers, the wound healing rate was significantly better with L-PRF treatment than traditional treatment. For later-stage treatment (third to fifth weeks), the overall cure rate was higher with L-PRF than the traditional treatment method. L-PRF can effectively promote wound healing in diabetic foot ulcers.