Piper longum L. ameliorates gout through the MAPK/PI3K-AKT pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Gout, a painful joint disease with a prevalence ranging from 0.86% to 2.2% in China over the past decade. Traditional medicine has long utilized the medicinal and edible Piper longum L. (PL) fruit spikes for treating gout and other joint conditions like rheumatoid arthritis. However, the exact mechanisms behind its effectiveness remain unclear. AIM OF THE STUDY: This study aimed to investigate the potential of alcoholic extracts from PL fruit spikes as a safe and effective treatment for gout. We used a combined network pharmacology and experimental validation approach to evaluate the mechanisms behind the anti-gout properties of PL. MATERIALS AND METHODS: UPLC-Q/TOF-MS analysis determined the major components of PL. Subsequently, network pharmacology analysis predicted potential molecular targets and related signaling pathways for the anti-gout activity of PL. Molecular docking simulations further explored the interactions between PL compounds and proteins and characterized the properties of potential bioactive secondary metabolites. Mouse models of air pouch inflammation and hyperuricemia were further established, and the anti-gout mechanism of PL was confirmed by examining the expression of proteins related to the MAPK and PI3K-AKT pathways in the tissue. RESULTS: Our analysis revealed 220 bioactive secondary metabolites within PL extracts. Network pharmacology and molecular docking results indicated that these metabolites primarily combat gout by modulating the PI3K-AKT and MAPK signaling pathways. In vivo experiments have also proven that PL at a dose of 100 mg/kg can optimally reduce acute inflammation of gout and kidney damage caused by high uric acid. The anti-gout mechanism involves the PI3K-AKT/MAPK signaling pathway and its downstream NF-κB pathway. CONCLUSION: This study provides compelling evidence for PL's therapeutic potential in gout management by modulating key inflammatory pathways. The findings offer a strong foundation for future clinical exploration of PL as a gout treatment option.

Subclinical damage to the contralateral eye in unilateral optic neuritis: A longitudinal study.

BACKGROUND: Early detection of subclinical injuries can lead to a correct diagnosis and help control the advancement of the condition. This study aims to investigate the presence of subclinical damage and silent progression to the contralateral eye's visual function and structure in patients experiencing their first episode of unilateral optic neuritis (ON). METHODS: Fifty patients with first-onset unilateral ON were enrolled in this study. Based on etiology, they were classified as having neuromyelitis optica spectrum disorder-related ON (NMOSD-ON), myelin oligodendrocyte glycoprotein antibody-associated ON (MOG-ON), idiopathic ON (IDON), or multiple sclerosis-related ON (MS-ON). These cases were followed up for one year to determine whether there was any silent progression of visual function and structure in the contralateral non-ON (NON) eye. A gender- and age-matched healthy control (HC) group was included to compare the differences in visual function and structure between the patients with NON eyes and the HC group. RESULTS: Within two weeks of onset, best-corrected visual acuity (BCVA; P = 0.008), mean deviation (MD) of the visual field (VF) (P = 0.001), and peripapillary retinal nerve fiber layer (pRNFL; P = 0.019) thickness were significantly worse in the NMOSD-NON patients than those in the HC group, while there were no differences in the pRNFL and the ganglion cell-inner plexiform layer (GCIPL) thicknesses and quadrant thicknesses (P > 0.05) of the groups. IDON-NON only showed subclinical damage in VF (P = 0.001) and temporal pRNFL (P = 0.042), while the BCVA, VF, and optic nerve structure (pRNFL, GCIPL) of the MOG-NON patients showed no subclinical damage (P > 0.05). In addition, the one-year follow-up of each NON eye type showed that there was no silent progression in NMOSD-NON, MOG-NON, or IDON-NON. A pairwise comparison of the different types of NON eyes revealed no statistical differences (P > 0.05). CONCLUSION: Among the patients with unilateral ON, NMOSD-NON and IDON-NON resulted in subclinical damage to the visual function and structure of the contralateral eye within two weeks of onset, whereas MOG-NON did not show any subclinical damage to visual function or structure. Furthermore, these subclinical damages did not show any silent progression during the one-year follow-up period.

Deep learning system for distinguishing optic neuritis from non-arteritic anterior ischemic optic neuropathy at acute phase based on fundus photographs.

Purpose: To develop a deep learning system to differentiate demyelinating optic neuritis (ON) and non-arteritic anterior ischemic optic neuropathy (NAION) with overlapping clinical profiles at the acute phase. Methods: We developed a deep learning system (ONION) to distinguish ON from NAION at the acute phase. Color fundus photographs (CFPs) from 871 eyes of 547 patients were included, including 396 ON from 232 patients and 475 NAION from 315 patients. Efficientnet-B0 was used to train the model, and the performance was measured by calculating the sensitivity, specificity, and area under the receiver operating characteristic curve (AUC). Also, Cohen's kappa coefficients were obtained to compare the system's performance to that of different ophthalmologists. Results: In the validation data set, the ONION system distinguished between acute ON and NAION achieved the following mean performance: time-consuming (23 s), AUC 0.903 (95% CI 0.827-0.947), sensitivity 0.796 (95% CI 0.704-0.864), and specificity 0.865 (95% CI 0.783-0.920). Testing data set: time-consuming (17 s), AUC 0.902 (95% CI 0.832-0.944), sensitivity 0.814 (95% CI 0.732-0.875), and specificity 0.841 (95% CI 0.762-0.897). The performance (κ = 0.805) was comparable to that of a retinal expert (κ = 0.749) and was better than the other four ophthalmologists (κ = 0.309-0.609). Conclusion: The ONION system performed satisfactorily distinguishing ON from NAION at the acute phase. It might greatly benefit the challenging differentiation between ON and NAION.

Potential anti-gout properties of Wuwei Shexiang pills based on network pharmacology and pharmacological verification.

ETHNOPHARMACOLOGICAL RELEVANCE: Wuwei Shexiang Pills (WWSX), a classic Tibetan medicine, consists of Chebulae Fructus (removed pit), Aucklandiae Radix, Moschus, Aconiti Fiavi Radix, and Acori Calami Rhizoma. It is used clinically in China to treat joint pain, swelling and other symptoms, and has the function of dispelling wind and relieving pain. However, to date, the mechanism of how it works against gout is still unclear. AIMS OF THE STUDY: Using network pharmacology, molecular docking and pharmacological verification to explore the potential anti-gout properties of WWSX. MATERIALS AND METHODS: With the use of UPLC-Q/TOF-MS, the main components of WWSX were obtained and screened for potential anti-inflammatory components by network pharmacology and molecular docking. The anti-inflammatory activity of the components screened from WWSX was also tested by in vitro assays. The anti-gout mechanism of WWSX was predicted by network pharmacology, and the pharmacological validation experiments using gouty arthritis model and mouse air pouch model were used to explore the multifaceted mechanism of WWSX to modify gout. RESULT: Thirty-eight active ingredients were obtained from the UPLC-Q/TOF-MS detection. The network pharmacology and molecular docking analysis showed that 104 co-targets were participated in the treatment of gout, and the main signaling pathways involved were NOD-like receptor pathway, NF-κB pathway and MAPK pathway. Pharmacological evaluation showed that WWSX could significantly improve gout in gouty arthritis models and mouse air pouch models by modulating the above pathways. CONCLUSION: This work has predicted and validated the anti-inflammatory material basis and predicted the anti-gout mechanism of WWSX which was verified by network pharmacology, molecular docking and in vitro cellular studies. The results reveal the mechanism of WWSX in the treatment of gout and provide a theoretical basis for its clinical application.

Influence of obstructive sleep apnea syndrome on the contralateral optic nerve in patients with unilateral nonarteritic anterior ischemic optic neuropathy.

STUDY OBJECTIVES: The aim was to quantitatively evaluate the influence of obstructive sleep apnea syndrome (OSAS) on the morphology and function of the contralateral optic nerve in patients with unilateral nonarteritic anterior ischemic optic neuropathy (NAION). METHODS: Fifty patients with unilateral NAION were divided into non-OSAS (n = 16), mild OSAS (n = 15), and moderate-severe OSAS (n = 19) groups based on their apnea-hypopnea index (AHI) scores. Systemic and ocular characteristics were compared between these groups. Spearman correlation and multiple linear regression analyses were used to determine the independent factors that most influenced the thickness of the peripapillary retinal nerve fiber layer (pRNFL). RESULTS: Body mass index and hypertension occurrence were higher in the moderate-severe OSAS group than in the non-OSAS group. Temporal pRNFL was thinner in the moderate-severe group than in the mild and non-OSAS groups, whereas no difference was found between the mild and non-OSAS groups. Spearman correlation showed that the AHI (r = -.469, P = .001) and the percentage of total sleep time with oxygen saturation < 90% (T90%; r = -.477, P = .001) correlated with temporal pRNFL thickness. Multiple linear regression showed that the AHI was negatively associated with temporal pRNFL thickness (ß = -0.573, P = .003). CONCLUSIONS: OSAS may cause subclinical temporal pRNFL thinning in the contralateral optic nerve among patients with unilateral NAION without any significant change in visual function. Advanced optic nerve observation and intervention may be warranted in patients with moderate-severe OSAS. CITATION: Li X, Zhang Y, Guo T, et al. Influence of obstructive sleep apnea syndrome on the contralateral optic nerve in patients with unilateral nonarteritic anterior ischemic optic neuropathy. J Clin Sleep Med. 2023;19(2):347-353.

Risk Factors for Fellow Eye Involvement in Patients with Nonarteritic Anterior Ischemic Optic Neuropathy.

INTRODUCTION: To investigate the possible risk factors for fellow eye involvement in patients with nonarteritic anterior ischemic optic neuropathy (NAION). METHODS: A total of 113 patients with unilateral NAION attack were included and divided into two groups according to whether fellow eye involvement was present over a mean follow-up period of 2.70 years (P25-P75: 0.77-3.54 years). General characteristics (including age, sex, diabetes, hypertension, hyperlipidemia and obstructive sleep apnea syndrome) and ocular characteristics (including initial best corrected visual acuity, initial visual field damage of the first eye and the presence/absence of a crowded disc) were analyzed and compared between the two groups. Cox regression was used to assess the risk factors for fellow eye involvement. RESULTS: During the follow-up period, 40 patients developed fellow eye involvement. The initial best corrected visual acuity (P = 0.048) and mean deviation (MD) of the visual field (VF) (P = 0.039) of the first eye in patients with fellow eye involvement were worse than those in patients without it. Diabetes (HR = 3.06, 95% CI: 1. 50, 6.26, P = 0.002) and increased VF damage (moderate vs. mild, HR = 2.92, 95% CI: 1.03, 8.25, P = 0.043; severe vs. mild, HR = 5.01, 95% CI: 1.65, 15.20, P = 0.004) were associated with a significantly increased risk of fellow eye involvement. In 57 patients with apnea hypopnea index (AHI) data for further study, an AHI score≥ 23.2 was also found to be a risk factor (HR = 3.36, 95% CI: 1.17, 9.69, P = 0.025). CONCLUSION: Diabetes, severer initial VF damage, and more severe obstructive sleep apnea syndrome (OSAS) were risk factors for fellow eye involvement in NAION. For patients with these risk factors, more intensive follow-ups might be warranted.

Different visual evoked potentials in neuromyelitis optica spectrum disorder-related optic neuritis and idiopathic demyelinating optic neuritis: a prospective longitudinal analysis.

BACKGROUND: To investigate different visual evoked potential (VEP) patterns in neuromyelitis optica spectrum disorder-related optic neuritis (NMOSD-ON) and idiopathic demyelinating optic neuritis (IDON). METHODS: This was a longitudinal, prospective, case-control study. Eighty-four Chinese patients with acute optic neuritis were enrolled, including 26 NMOSD-ON patients and 58 IDON patients. All the patients underwent best-corrected visual acuity (BCVA) and full-field pattern reversal VEP recordings at the onset, 1 month, 3 months, and 6 months. RESULTS: Within 15' checks, the NMOSD-ON patients had more severe VEP amplitude reduction at 6 months (2.39 ± 4.63 µV vs. 6.96 ± 8.88 µV, P = 0.034). However, the IDON patients showed more frequently normal VEP response at 3 months (24.0% vs. 4.5%, P = 0.017), and only prolonged P100 peak latency with normal amplitude (L) at 6 months (30.0% vs. 57.8%, P = 0.048). Within 60' checks, no significant difference in VEP parameters between the two groups was found at each follow-up (P > 0.05). CONCLUSIONS: The NMOSD-ON patients showed more severe axonal damage and worse axonal recovery than the IDON patients. VEP elicited by smaller check size was more sensitive to visual pathway abnormality in NMOSD-ON.

Comparing evolvement of visual field defect in neuromyelitis optica spectrum disorder-optic neuritis and idiopathic optic neuritis: a prospective study.

PURPOSE: To compare the evolvement of visual field (VF) defect in neuromyelitis optica spectrum disorder-optic neuritis (NMOSD-ON) and idiopathic optic neuritis (IDON). METHODS: This prospective study involved 104 optic neuritis (ON) patients followed up for ≥ 6 months (33 patients with NMOSD-ON and 71 patients with IDON). The pattern and recovery pattern of VF defect, mean defect (MD) and pattern standard deviation (PSD) of VF, as well as BCVA at onset, 1 month (1 m), 3 months (3 m), and ≥ 6 months (6 m) after onset were compared between two groups. Analysis of these indicators in first episode patients was also done. RESULTS: Diffuse abnormalities and nerve fiber bundle abnormalities were the two most common patterns in both groups. The percentage of neurologic abnormality of VF defect in NMOSD-ON was higher than that of IDON. Compared with the IDON group, the MD and PSD of NMOSD-ON group were significantly worse at each follow-up. While a positive correlation in BCVA was found between 1 m and ≥ 6 m in the NMOSD-ON group only, a positive correlation was found between 1 m and ≥ 6 m in MD and PSD of both groups. A positive correlation was found between 3 m and ≥ 6 m in MD, PSD and BCVA of both groups. The quadrant recovery pattern was the most common pattern in both groups (57.1% in NMOSD-ON and 57.4% in IDON). The analysis of the first episode subgroup further confirmed the observation above. CONCLUSIONS: The NMOSD-ON patients tended to suffer more severe VF damage, VF irregularity and worse prognosis than that of IDON patients. Diffuse abnormalities and nerve fiber bundle abnormalities were the two most common types in both groups, while neurologic abnormality more common in NMOSD-ON and central scotoma more common in IDON. The visual functions of 1 m in NMOSD-ON and 3 m in IDON were related to its prognosis.

Remedial Effect of Intravenous Cyclophosphamide in Corticosteroid-Refractory Patients in the Acute Phase of Neuromyelitis Optica Spectrum Disorder-Related Optic Neuritis.

Background: To investigate the remedial efficacy and safety of intravenous cyclophosphamide (CP) in the acute phase in patients with neuromyelitis optica spectrum disorder-related optic neuritis (NMOSD-ON) who are refractory to intravenous methylprednisolone (MP) treatment. Design: This study was a single-center, retrospective, observational case-control cohort study. Methods: Thirty-six patients who had acute NMOSD-ON attacks and were refractory to MP treatment were included. Patents were divided into two groups: the remedial CP group, and the MP group. The best-corrected visual acuity (BCVA), mean deviation (MD) of the visual field (VF), visual evoked potential amplitude (VEP-A), visual evoked potential latency (VEP-T), and average thickness of the retinal nerve fiber layer (RNFL) at onset, 1 month (m), 3 m, and 6 m after the attack were analyzed. Routine blood test results, liver and kidney function, routine urinalysis results and general condition were analyzed for safety issues at each follow-up. Fisher's exact test, the Mann-Whitney U test, the Kruskal-Wallis test and the Wilcoxon rank-sum test were used for statistical analysis. Results: The remedial CP group showed significant improvement over 6 m with regard to BCVA and MD (P < 0.05),whereas MP group only showed significant improvement in MD (P < 0.05). Regarding remedial CP intervention time window, the CP ≤ 30 days group showed significant improvement over 6 m with regard to BCVA (P = 0.002), MD (P = 0.003), and VEP-A (P = 0.036), while those CP > 30 days group did not. Both two subgroups showed significantly RNFL thickness reduction, however, BCVA, MD, VEP-A, VEP-T, and RNFL thickness showed no significant differences between the two subgroups at any follow-up point (P > 0.05). Conclusion: CP within 30 days of attack onset is safe and might have a beneficial degree of therapeutic efficacy for acute-phase treatment of NMOSD-ON that is refractory to MP treatment alone.