Cannabidiol alleviates carbon tetrachloride-induced liver fibrosis in mice by regulating NF-κB and PPAR-α pathways.

Liver fibrosis has become a serious public health problem that can develop into liver cirrhosis and hepatocellular carcinoma and even lead to death. Cannabidiol (CBD), which is an abundant nonpsychoactive component in the cannabis plant, exerts cytoprotective effects in many diseases and under pathological conditions. In our previous studies, CBD significantly attenuated liver injury induced by chronic and binge alcohol in a mouse model and oxidative bursts in human neutrophils. However, the effects of CBD on liver fibrosis and the underlying mechanisms still need to be further explored. A mouse liver fibrosis model was induced by carbon tetrachloride (CCl4) for 10 weeks and used to explore the protective properties of CBD and related molecular mechanisms. After the injection protocol, serum samples and livers were used for molecular biology, biochemical and pathological analyses. The results showed that CBD could effectively improve liver function and reduce liver damage and liver fibrosis progression in mice; the expression levels of transaminase and fibrotic markers were reduced, and histopathological characteristics were improved. Moreover, CBD inhibited the levels of inflammatory cytokines and reduced the protein expression levels of p-NF-κB, NF-κB, p-IκBα, p-p38 MAPK, and COX-2 but increased the expression level of PPAR-α. We found that CBD-mediated protection involves inhibiting NF-κB and activating PPAR-α. In conclusion, these results suggest that the hepatoprotective effects of CBD may be due to suppressing the inflammatory response in CCl4-induced mice and that the NF-κB and PPAR-α signaling pathways might be involved in this process.

Comparison of the connectivity of the posterior intralaminar thalamic nucleus and peripeduncular nucleus in rats and mice.

The posterior intralaminar thalamic nucleus (PIL) and peripeduncular nucleus (PP) are two adjoining structures located medioventral to the medial geniculate nucleus. The PIL-PP region plays important roles in auditory fear conditioning and in social, maternal and sexual behaviors. Previous studies often lumped the PIL and PP into single entity, and therefore it is not known if they have common and/or different brain-wide connections. In this study, we investigate brain-wide efferent and afferent projections of the PIL and PP using reliable anterograde and retrograde tracing methods. Both PIL and PP project strongly to lateral, medial and anterior basomedial amygdaloid nuclei, posteroventral striatum (putamen and external globus pallidus), amygdalostriatal transition area, zona incerta, superior and inferior colliculi, and the ectorhinal cortex. However, the PP rather than the PIL send stronger projections to the hypothalamic regions such as preoptic area/nucleus, anterior hypothalamic nucleus, and ventromedial nucleus of hypothalamus. As for the afferent projections, both PIL and PP receive multimodal information from auditory (inferior colliculus, superior olivary nucleus, nucleus of lateral lemniscus, and association auditory cortex), visual (superior colliculus and ectorhinal cortex), somatosensory (gracile and cuneate nuclei), motor (external globus pallidus), and limbic (central amygdaloid nucleus, hypothalamus, and insular cortex) structures. However, the PP rather than PIL receives strong projections from the visual related structures parabigeminal nucleus and ventral lateral geniculate nucleus. Additional results from Cre-dependent viral tracing in mice have also confirmed the main results in rats. Together, the findings in this study would provide new insights into the neural circuits and functional correlation of the PIL and PP.

Effectiveness and Safety of Anlotinib Combined with PD-1 Blockades in Patients with Previously Immunotherapy Treated Advanced Non-Small Cell Lung Cancer: A Retrospective Exploratory Study.

Objective: This study aimed to investigate the effectiveness and tolerability of anlotinib plus PD-1 blockades in patients with previously immunotherapy treated advanced non-small-cell lung cancer (NSCLC). Methods: A total of 67 patients with previously immunotherapy treated advanced NSCLC who received anlotinib plus PD-1 blockades in clinical practice were screened retrospectively. All the PD-1 blockades used in this study were approved in China and consisted of sintilimab, camrelizumab, tislelizumab and pembrolizumab. Effectiveness and safety of anlotinib plus PD-1 blockades were assessed, and all patients were followed up regularly. Clinical significance between response status to previous immune-related treatment regimens and therapeutic outcomes of anlotinib plus PD-1 blockades was further explored. Results: The best overall response among the 67 patients suggested that a partial response was observed in 16 patients, stable disease was noted in 41 patients and progressive disease was found in 10 patients, which yielded an objective response rate of 23.9% (95% CI: 14.3-35.9%) and a disease control rate of 85.1% (95% CI: 74.3-92.6%). Prognostic outcomes indicated that the median progression-free survival (PFS) was 6.1 months (95% CI: 2.37-9.83) and the median overall survival (OS) was 16.5 months (95% CI: 10.73-22.27). Exploratory analysis highlighted that patients who were intolerant to previous immune-related regimens (17 patients) might have a superior prognosis (median OS: 22.3 months vs 12.5 months, P=0.024). Additionally, adverse reactions with any grades during anlotinib plus PD-1 blockades administration were observed in 62 patients (92.5%), of which 31 patients (46.3%) had ≥grade 3 adverse reactions. Most common adverse reactions were fatigue, hypertension, diarrhea and hepatotoxicity. Conclusion: Anlotinib plus PD-1 blockades demonstrated promising effectiveness and tolerable safety in patients with previously immunotherapy treated advanced NSCLC. Those who were intolerant to previous immune-related regimens might benefit significantly from treatment with anlotinib plus PD-1 blockades. This conclusion should be confirmed in future studies.

Carbon Dot-Mediated Photodynamic Treatment Improves the Quality Attributes of Post-Harvest Goji Berries (Lycium barbarum L.) via Regulating the Antioxidant System.

Carbon dots (CDs) have been proposed as photosensitizers in photodynamic treatment (PDT), owing to their excellent biological attributes and budding fruit preservation applications. In the present study, CDs (4.66 nm) were synthesized for photodynamic treatment to improve the quality attributes in post-harvest goji berries. The prepared CDs extended the storage time of the post-harvest goji berries by 9 d. The CD-mediated PDT postponed the hardness and decay index loss, reduced the formation of malondialdehyde (MDA), hydrogen peroxide (H2O2), and superoxide anion (O2•-) significantly, and delayed the loss of vital nutrients like the total protein, phenols, and flavonoids. The CD-mediated PDT improved the catalase (CAT), ascorbate peroxidase (APX), peroxidase (POD), phenylalanine ammonia-lyase (PAL), glutathione reductase (GR), and superoxide dismutase (SOD) activities, but did not improve polyphenol oxidase (PPO) activity. In addition, The CD-mediated PDT induced the accumulation of ascorbic acid (ASA) and glutathione (GSH). Overall, a CD-mediated PDT could extend the storage time and augment the quality attributes in post-harvest fresh goji berries by regulating the antioxidant system.

Artemisinin ameliorates cognitive decline by inhibiting hippocampal neuronal ferroptosis via Nrf2 activation in T2DM mice.

BACKGROUND: Neuronal ferroptosis plays a critical role in the pathogenesis of cognitive deficits. The present study explored whether artemisinin protected type 2 diabetes mellitus (T2DM) mice from cognitive impairments by attenuating neuronal ferroptosis in the hippocampal CA1 region. METHODS: STZ-induced T2DM mice were treated with artemisinin (40 mg/kg, i.p.), or cotreated with artemisinin and Nrf2 inhibitor MEL385 or ferroptosis inducer erastin for 4 weeks. Cognitive performance was determined by the Morris water maze and Y maze tests. Hippocampal ROS, MDA, GSH, and Fe2+ contents were detected by assay kits. Nrf2, p-Nrf2, HO-1, and GPX4 proteins in hippocampal CA1 were assessed by Western blotting. Hippocampal neuron injury and mitochondrial morphology were observed using H&E staining and a transmission electron microscope, respectively. RESULTS: Artemisinin reversed diabetic cognitive impairments, decreased the concentrations of ROS, MDA and Fe2+, and increased the levels of p-Nr2, HO-1, GPX4 and GSH. Moreover, artemisinin alleviated neuronal loss and ferroptosis in the hippocampal CA1 region. However, these neuroprotective effects of artemisinin were abolished by Nrf2 inhibitor ML385 and ferroptosis inducer erastin. CONCLUSION: Artemisinin effectively ameliorates neuropathological changes and learning and memory decline in T2DM mice; the underlying mechanism involves the activation of Nrf2 to inhibit neuronal ferroptosis in the hippocampus.

Corynoline Suppresses Osteoclastogenesis and Attenuates ROS Activities by Regulating NF-κB/MAPKs and Nrf2 Signaling Pathways.

Declining estrogen production in postmenopausal females causes osteoporosis in which the resorption of bone exceeds the increase in bone formation. Although clinical drugs are currently available for the treatment of osteoporosis, sustained medication use is accompanied by serious side effects. Corydalis bungeana Herba, a famous traditional Chinese herb listed in the Chinese Pharmacopoeia Commission, constitutes various traditional Chinese Medicine prescriptions, which date back to thousands of years. One of the primary active components of C. bungeana Turcz. is Corynoline (Cor), a plant isoquinoline alkaloid derived from the Corydalis species, which possesses bone metabolism disease therapeutic potential. The study aimed at exploring the effects as well as mechanisms of Cor on osteoclast formation and bone resorption. TRAcP staining, F-actin belt formation, and pit formation were employed for assessing the osteoclast function. Western blot, qPCR, network pharmacology, and docking analyses were used for analyzing the expression of osteoclast-associated genes and related signaling pathways. The study focused on investigating how Cor affected OVX-induced trabecular bone loss by using a mouse model. Cor could weaken osteoclast formation and function by affecting the biological receptor activators of NF-κB and its ligand at various concentrations. Mechanistically, Cor inhibited the NF-κB activation, and the MAPKs pathway stimulated by RANKL. Besides, Cor enhanced the protein stability of the Nrf2, which effectively abolished the RANKL-stimulated ROS generation. According to an OVX mouse model, Cor functions in restoring bone mass, improving microarchitecture, and reducing the ROS levels in the distal femurs, which corroborated with its in vitro antiosteoclastogenic effect. The present study indicates that Cor may restrain osteoclast formation and bone loss by modulating NF-κB/MAPKs and Nrf2 signaling pathways. Cor was shown to be a potential drug candidate that can be utilized for the treatment of osteoporosis.

Cannabidiol regulates the activation of hepatic stellate cells by modulating the NOX4 and NF-κB pathways.

Cannabidiol (CBD) is an extract of natural cannabinoids that has therapeutic implications for a variety of ailments, such as neurological diseases, cardiomyopathy, and diabetes, due to its strong anti-inflammatory and oxidative stress properties. Our purpose was to reveal the possible underlying mechanisms and effect of CBD on the glucose oxidase (GO)-induced activation of HSC-T6 and LX-2 cells. The results showed that CBD effectively inhibited the proliferation and activation of HSC-T6 and LX-2 cells, and reduced the production of profibrotic factors to different degrees. CBD disrupted the NOX4 signalling pathway in activated HSC-T6 and LX-2 cells, reduced ROS and MDA levels, and increased SOD and GSH levels, thereby stabilizing the oxidative imbalance. CBD significantly inhibited the phosphorylation and degradation of NF-κB and IκBα, and decreased the release of TNF-α, IL-1ß and IL-6. Moreover, CBD and an NF-κB-specific inhibitor (CAPE) effectively inhibited the expression of α-SMA, COL I, TNF-α and IL-1ß to promote collagen metabolism and inhibit the inflammatory response. Overall, CBD inhibited HSCs activation through a and the mechanism involving the inhibition of NOX4 and NF-κB-dependent ROS regulation, thereby reducing inflammation and ameliorating oxidative imbalances.

Aldehyde oxidase 1 promotes gallbladder carcinogenesis through ROS-mediated activation of the Wnt/ß-catenin pathway.

BACKGROUND: Aldehyde oxidase 1 (AOX1) is associated with various pathophysiological processes, including cancer. Specifically, AOX1 has been demonstrated to have a close relationship with the progression of certain cancers. However, the expression, function, and mechanisms of action of AOX1 in gallbladder cancer (GBC) remain unclear. METHODS: Utilizing immunohistochemistry, the study quantified the prevalence of AOX1 within tissues of gallbladder carcinoma and those of the surrounding non-cancerous regions. In vitro assays using gallbladder carcinoma cell lines with modulated AOX1 expression levels were performed to assess the protein's role in cell proliferation, migration, and invasion. Furthermore, flow cytometry techniques were harnessed to determine the influence of AOX1 on the content of reactive oxygen species (ROS) in these cells. Additionally, the expression of epithelial-mesenchymal transition (EMT) markers and the Wnt/ß-catenin signaling pathway markersin cells with varied AOX1 expression, detected through Western blot analyses. An in vivo xenograft model involving athymic mice was implemented to explore the influence of AOX1 on gallbladder tumor growth, with Western blot analysis applied to measure EMT marker expression in the resulting tumours. RESULTS: Elevated AOX1 protein levels have been observed in gallbladder carcinoma tissues, with such upregulation linked to a negative prognostic outlook for patients. In vitro analyses demonstrate that enhanced AOX1 expression facilitates gallbladder carcinoma cell proliferation, migration, and invasion, while AOX1 suppression yields an inhibitory effect on these cellular behaviors. Western blot results reveal an inverse relationship between AOX1 and E-cadherin levels, yet was positively correlation with N-cadherin, Vimentin, and Snail within both gallbladder cancer cells and in vivo xenograft tumours. Further mechanistic investigation indicates that AOX1 elevation augments reactive oxygen species (ROS) production and initiates the Wnt/ß-catenin signaling pathway in these cells. The application of N-acetylcysteine (NAC) and/or KY1797K attenuates the proliferative, migratory, and invasive enhancements imparted by AOX1 overexpression and reinforces these effects when AOX1 is silenced-achieved through ROS mitigation and the obstruction of the Wnt/ß-catenin pathway. In vivo studies corroborate these findings, showing AOX1 overexpression to amplify xenograft tumor growth and mesenchymal marker expression, whereas AOX1 interference did the opposite. CONCLUSIONS: The study indicates that AOX1 functions as a carcinogenic factor in gallbladder carcinoma, enhancing cell proliferation, migration, invasion, and the EMT. These effects are driven by the activation of the Wnt/ß-catenin pathway mediated by reactive oxygen species (ROS). Therefore,AOX1 presents potential as a valuable prognostic and diagnostic marker as well as a target for therapeutic intervention in the gallbladder cancer.

Research hotspots and trends of transcranial magnetic stimulation in Parkinson's disease: a bibliometric analysis.

Background: Transcranial magnetic stimulation (TMS), as a non-invasive neuromodulation technique, has been widely used in the treatment of Parkinson's disease (PD). The increasing application of TMS has promoted an increasing number of clinical studies. In this paper, a bibliometric analysis of existing studies was conducted to reveal current research hotspots and guide future research directions. Method: Relevant articles and reviews were obtained from the Science Citation Index Expanded of Web of Science Core Collection database. Data related to publications, countries, institutions, authors, journals, citations, and keywords in the studies included in the review were systematically analyzed using VOSviewer 1.6.18 and Citespace 6.2.4 software. Result: A total of 1,894 papers on the topic of TMS in PD between 1991 and 2022 were analyzed and visualized to identify research hotspots and trends in the field. The number of annual publications in this field of study has increased gradually over the past 30 years, with the number of annual publications peaking in 2022 (n = 150). In terms of publications and total citations, countries, institutions, and authors from North America and Western Europe were found to make significant contributions to the field. The current hotspot focuses on the effectiveness of TMS for PD in different stimulation modes or different stimulated brain regions. The keyword analysis indicates that the latest research is oriented to the mechanism study of TMS for motor symptoms in PD, and the non-motor symptoms are also receiving more attention. Conclusion: Our study offers insights into the current hotspots and emerging trends of TMS in the rehabilitation of PD. These findings may serve as a guide for future research and the application of TMS for PD.

Cinnamaldehyde Alleviates Bone Loss by Targeting Oxidative Stress and Mitochondrial Damage via the Nrf2/HO-1 Pathway in BMSCs and Ovariectomized Mice.

Osteoporosis (OP) is typically brought on by disruption of bone homeostasis. Excessive oxidative stress and mitochondrial dysfunction are believed to be the primary mechanisms underlying this disorder. Therefore, in order to restore bone homeostasis effectively, targeted treatment of oxidative stress and mitochondrial dysfunction is necessary. Cinnamaldehyde (CIN), a small molecule that acts as an agonist for the nuclear factor erythroid 2-related factor (Nrf2), has been found to possess antiapoptotic, anti-inflammatory, and antioxidant properties. We found that CIN, while rescuing apoptosis, can also reduce the accumulation of reactive oxygen species (ROS) to improve mitochondrial dysfunction and thus restore the osteogenic differentiation potential of BMSCs disrupted by hydrogen peroxide (H2O2) exposure. The role of CIN was preliminarily considered to be a consequence of Nrf2/HO-1 axis activation. The ovariectomized mice model further demonstrated that CIN treatment ameliorated oxidative stress in vivo, partially reversing OVX-induced bone loss. This improvement was seen in the trabecular microarchitecture and bone biochemical indices. However, when ML385 was concurrently injected with CIN, the positive effects of CIN were largely blocked. In conclusion, this study sheds light on the intrinsic mechanisms by which CIN regulates BMSCs and highlights the potential therapeutic applications of these findings in the treatment of osteoporosis.

Bioinformatics-based analysis reveals elevated CYTL1 as a potential therapeutic target for BRAF-mutated melanoma.

Introduction: Despite many recent emerging therapeutic modalities that have prolonged the survival of melanoma patients, the prognosis of melanoma remains discouraging, and further understanding of the mechanisms underlying melanoma progression is needed. Melanoma patients often have multiple genetic mutations, with BRAF mutations being the most common. In this study, public databases were exploited to explore a potential therapeutic target for BRAF-mutated melanoma. Methods: In this study, we analyzed differentially expressed genes (DEGs) in normal tissues and melanomas, Braf wild-type and Braf mutant melanomas using information from TCGA databases and the GEO database. Subsequently, we analyzed the differential expression of CYTL1 in various tumor tissues and its effect on melanoma prognosis, and resolved the mutation status of CYTL1 and its related signalling pathways. By knocking down CYTL1 in melanoma cells, the effects of CYTL1 on melanoma cell proliferation, migration and invasion were further examined by CCK8 assay, Transwell assay and cell migration assay. Results: 24 overlapping genes were identified by analyzing DEGs common to melanoma and normal tissue, BRAF-mutated and BRAF wild-type melanoma. Among them, CYTL1 was highly expressed in melanoma, especially in BRAF-mutated melanoma, and the high expression of CYTL1 was associated with epithelial-mesenchymal transition (EMT), cell cycle, and cellular response to UV. In melanoma patients, especially BRAF-mutated melanoma patients, clinical studies showed a positive correlation between increased CYTL1 expression and shorter overall survival (OS) and disease-free survival (DFS). In vitro experiments further confirmed that the knockdown of CYTL1 significantly inhibited the migration and invasive ability of melanoma cells. Conclusion: CYTL1 is a valuable prognostic biomarker and a potentially effective therapeutic target in melanoma, especially BRAF-mutated melanoma.

Evaluation and uncertainty analysis of Himawari-8 hourly aerosol product version 3.1 and its influence on surface solar radiation before and during the COVID-19 outbreak.

The hourly Himawari-8 version 3.1 (V31) aerosol product has been released and incorporates an updated Level 2 algorithm that uses forecast data as an a priori estimate. However, there has not been a thorough evaluation of V31 data across a full-disk scan, and V31 has yet to be applied in the analysis of its influence on surface solar radiation (SSR). This study firstly investigates the accuracy of V31 aerosol products, which includes three categories of aerosol optical depth (AOD) (AODMean, AODPure, and AODMerged) as well as the corresponding Ångström exponent (AE), using ground-based measurements from the AERONET and SKYNET. Results indicate that V31 AOD products are more consistent with ground-based measurements compared to previous products (V30). The highest correlation and lowest error were seen in the AODMerged, with a correlation coefficient of 0.8335 and minimal root mean square error of 0.1919. In contrast, the AEMerged shows a larger discrepancy with measurements unlike the AEMean and AEPure. Error analysis reveals that V31 AODMerged has generally stable accuracy across various ground types and geometrical observation angles, however, there are higher uncertainties in areas with high aerosol loading, particularly for fine aerosols. The temporal analysis shows that V31 AODMerged performs better compared to V30, particularly in the afternoon. Finally, the impacts of aerosols on SSR based on the V31 AODMerged are investigated through the development of a sophisticated SSR estimation algorithm in the clear sky. Results demonstrate that the estimated SSR is significant consistency with those of well-known CERES products, with preservation of 20 times higher spatial resolution. The spatial analysis reveals a significant reduction of AOD in the North China Plain before and during the COVID-19 outbreak, resulting in an average 24.57 W m-2 variation of the surface shortwave radiative forcing in clear sky daytime.

Targeted activation of Nrf2/HO-1 pathway by Corynoline alleviates osteoporosis development.

Oxidative stress is preferentially treated as a risk factor for the development and progression of osteoporosis. Corynoline as a component of Corydalis bungeana Turcz presents antioxidative and anti-inflammatory properties. In the present study, the effects of Corynoline on osteoblasts following hydrogen peroxide (H2O2)-induced injury were evaluated accompanied by the investigation of the molecular mechanisms involved. It was found that Corynoline downregulated the intracellular reactive oxygen species (ROS) generation and restored the osteogenic potential of the disrupted osteoblasts by H2O2 exposure. Furthermore, Corynoline was revealed to activate the Nrf2/HO-1 signaling pathway, while ML385 (an Nrf2 inhibitor) would prevent the Corynoline-mediated positive effects on the disrupted osteoblasts. In terms of the animal experiments, Corynoline treatment contributed to a significantly alleviated bone loss. These findings indicate that Corynoline may significantly attenuate the H2O2-induced oxidative damage of osteoblasts via the Nrf2/HO-1 signaling pathway, providing novel insights to the development of treatments for osteoporosis induced by oxidative injury.

Antibacterial Activity and Possible Mechanism of Litsea cubeba Essential Oil Against Shigella sonnei and Its Application in Lettuce.

Shigella sonnei, the causative agents of bacillary dysentery, remains a significant threat to public health. Litsea cubeba essential oil (LC-EO), one of the natural essential oils, exhibited promising biological activities. In this study, the antibacterial effects and possible mechanisms of LC-EO on S. sonnei and its application in lettuce medium were investigated. The minimum inhibitory concentration (MIC) of LC-EO against S. sonnei ATCC 25931 and CMCC 51592 was 4 and 6 µL/mL, respectively. The LC-EO could inhibit the growth of S. sonnei, and decreased S. sonnei to undetectable levels with 4 µL/mL for 1 h in Luria-Bertani broth. The antibacterial mechanism indicated that after the treatment of LC-EO, the production of reactive oxygen species and the activity of superoxide dismutase were significantly elevated in S. sonnei cells, and eventually led to the lipid oxidation product, the malondialdehyde content that significantly increased. Moreover, LC-EO at 2 MIC could destroy 96.51% of bacterial cell membrane integrity, and made S. sonnei cells to appear wrinkled with a rough surface, so that the intracellular adenosine triphosphate leakage was about 0.352-0.030 µmol/L. Finally, the results of application evaluation indicated that the addition of LC-EO at 4 µL/mL in lettuce leaves and 6 µL/mL in lettuce juice could decrease the number of S. sonnei to undetectable levels without remarkable influence on the lettuce leaf sensory quality. In summary, LC-EO exerted strong antibacterial activity and has the potential to control S. sonnei in food industry.

Structural characterization and stability of glycated bovine serum albumin-kaempferol nanocomplexes.

Kaempferol (Kae), a flavonoid is endowed with various functions. However, due to its poor water solubility and stability, its application in the food and pharmaceutical fields remains elusive. Emerging reports have emphasized the importance of bovine serum albumin (BSA), and glycosylated BSA (GBSA) prepared in the nature deep eutectic solvent system as drug delivery system carriers. In our study, ultraviolet and fluorescence spectra revealed the higher interactions of BSA and GBSA with Kae. Through analysis of Z-average diameter, zeta-potential, polydispersity index (PDI), encapsulation efficiency (EE), loading capacity (LC) of BSA-Kae nanocomplexes (NPs) and GBSA-Kae NPs, GBSA-Kae NPs showed a higher absolute value of zeta-potential and lower PDI, while its EE and LC were also higher. Structural characterization and stability analysis revealed that GBSA-Kae NPs had more stable properties. This study laid the theoretical foundation for improving the solubility and stability of Kae during its delivery and transport.

Effects of slanted bilateral lateral recession vs conventional bilateral lateral recession on convergence insufficiency intermittent exotropia: a prospective study.

AIM: To observe the surgical effects of slanted bilateral lateral recession (S-BLR) versus conventional bilateral lateral recession (C-BLR) in convergence insufficiency intermittent exotropia (CI-IXT). METHODS: Using a randomized, double-blind, prospective design, 22 patients with CI-IXT who were admitted to Renmin Hospital of Wuhan University from July 2019 to December 2020 were included. Patients were randomly divided into either S-BLR or C-BLR group for their subsequent strabismus surgery. All patients were followed up for 12mo. Near deviation, distant deviation, and near-distance difference (NDD) were measured in all patients. RESULTS: Twelve months after surgery, NDD improvement was 10 (8, 13) prismatic degrees (PD) in S-BLR group and 3 (1, 6) PD in C-BLR group (P=0.011). The near deviation of S-BLR group was 0 (-2, 2) PD, while that of C-BLR group was -4 (-6, -3) PD (P=0.005). Before and after surgery, the difference in the distant deviation between the two groups was not statistically significant. There was no statistically significant difference in near stereopsis between the two groups (P=0.380) at 12mo. The success rate at 12mo after operation was 90.91% and 72.73% in the two groups (P=0.280). CONCLUSION: CI-IXT patients treated with S-BLR have better surgical outcomes than those treated with C-BLR, which indicates S-BLR is a safe and effective operation pattern.

Integrated miRNA and mRNA omics reveal dioscin suppresses migration and invasion via MEK/ERK and JNK signaling pathways in human endometrial carcinoma in vivo and in vitro.

ETHNOPHARMACOLOGICAL RELEVANCE: Polygonatum sibiricum Redouté (PS, also called Huangjing in traditional Chinese medicine), is a perennial herb as homology of medicine and food. According to the traditional Chinese medicine theory "Special Records of Famous Doctors", its functions include invigorating qi and nourishing yin, tonifying spleen and kidney. Traditionally, qi and blood therapy has been believed as most applicable to the treatment of uterine disease. The current research has focused on the effect and mechanism of dioscin, the main active component of PS, on Endometrial carcinoma (EC). AIM OF THE STUDY: To study the efficacy of dioscin on proliferation and migration of Endometrial carcinoma cell line, we conducted experiments by using xenograft model and Ishikawa cells, and explored the potential molecular mechanism. MATERIALS AND METHODS: mRNA and miRNA omics techniques were employed to investigate the regulatory mechanism of dioscin on EC Ishikawa cells. Based on in vivo and in vitro experiments, cell clone formation, cell scratching, Transwell, H&E staining, immunohistochemistry, q-PCR, and Western blot techniques were used to determine the molecular effects and mechanisms of dioscin on cell migration. RESULTS: Integrated miRNA and mRNA omics data showed that 513 significantly different genes marked enrichment in MAPK signaling pathway. The in vivo data showed that dioscin (24 mg/kg) significantly inhibited tumor growth. The in vitro proliferation and invasiveness of dioscin on Ishikawa cells showed that dioscin could significantly decrease the colony numbers, and suppress the Ishikawa cell wound healing, migration and invasion. Molecular data revealed that dioscin decreased the MMP2 and MMP9 expression in vitro and in vivo. The p-MEK, p-ERK, and p-JNK expression levels were also confirmed to be significantly reduced. Key regulators in the MAPK signaling pathway were further validated in xenograft tumors. CONCLUSION: Our data indicated that dioscin inhibited Ishikawa cell migration and invasion mediated through MEK/ERK and JNK signaling. More importantly, screened hub miRNAs and genes can be regarded as potential molecular targets for future EC treatment.

Evolutionary research trend of Polygonatum species: a comprehensive account of their transformation from traditional medicines to functional foods.

With the advances in Polygonatum research, there is a huge interest in harnessing the valuable functional ingredients of this genus with the potential for functional foods. This review emphasizes the different aspects of Ploygonatum based research starting from its bioactive compounds, their structural characterization, various extraction methods, as well as biological activities. In view of its integral use as an essential medicinal plant, our review emphasizes on its promising food applications both as an ingredient and as a whole food, and its improved health benefits with potential for agricultural and environmental relevance are also discussed. As we collated the recent research information, we present the main challenges and limitations of the current research trend in this area which can upgrade the further expansion of Polygonatum-related research that will strengthen its economic and accessible nutritional value in the food and health industries. By highlighting the need for the unattended species, this review not only fills existing research gaps, but also encourages the researchers to find new avenues for the natural production of bio-based functional materials and the development of highly functional and health-promoting foods for disease prevention and treatment.

Lycium barbarum (Goji) as functional food: a review of its nutrition, phytochemical structure, biological features, and food industry prospects.

Lycium genus (Goji berry) is recognized as a good source of homology of medicine and food, with various nutrients and phytochemicals. Lately, numerous studies have focused on the chemical constituents and biological functions of the L. barbarum L., covering phytochemical and pharmacological aspects. We aim to provide exclusive data on the nutrients of L. barbarum L. fruits and phytochemicals, including their structural characterization, the evolution of extraction, and purification processes of different phytochemicals of L. barbarum L. fruit while placing greater emphasis on their wide-ranging health effects. This review also profitably offers innovative approaches for the food industry and industrial applications of L. barbarum L. and addresses some current situations and problems in the development of L. barbarum L. in deep processing products, which can provide clues for the sustainable development of L. barbarum L. industry.

Exercise therapy for adolescent idiopathic scoliosis rehabilitation: a bibliometric analysis (1999-2023).

Background: Among the conservative treatments for rehabilitation of adolescent idiopathic scoliosis (AIS), exercise therapy has attracted a large number of studies as its advantages of good clinical effect, high operability, high compliance, few side effects and low cost. We conduct a bibliometric analysis of previous research to identify prevalent areas of study and inform research for the future directions in this paper. Methods: Relevant publications and reviews were collected using the Science Citation Index Expanded from the Web of Science Core Collection. Information from the included studies was analyzed systematically using VOSviewer and Citespace software to identify patterns regarding publications, keywords, authors, citations, countries, institutions and journals. Results: A total of 172 articles published from 1999 to 2023 were identified. Over the last decade, the number of publications has gradually increased, reaching a peak of 21 publications in 2021. China, North America and Western European countries and institutions are leading the way as far as the quantity of publications and the total number of citations are concerned. The current areas of focus are the efficacy of exercise therapy in relation to enhancing the quality of life of adolescents during rehabilitation. Conclusions: This is the first bibliometric analysis that provides a comprehensive review of the research trends and advances in exercise therapy for the rehabilitation of AIS. The study identifies latest research frontiers and hot directions, providing a valuable reference for scholars in the field of exercise therapy.