Celastrol assuages oxygen-glucose deprivation and reoxygenation-induced damage in human brain microvascular endothelial cells through the circDLGAP4/miR-6085/GDF11 pathway.

The effect of Celastrol on cerebral ischemia-reperfusion remains unknown. The study aims to explore the role of circular RNA DLGAP4 (circDLGAP4) in cerebral ischemia-reperfusion and the underlying mechanism. Ischemia-reperfusion (I/R) injury of human brain microvascular endothelial cells (HBMECs) was induced by oxygen-glucose deprivation and reoxygenation (OGD/R). Reverse transcription quantitative real-time PCR (RT-qPCR) and western blotting analysis were performed to detect the expression of circDLGAP4, microRNA-6085 (miR-6085), growth differentiation factor 11 (GDF11), B-cell lymphoma-2 (BCL2) and BCL2-associated x protein (BAX). Cell viability, proliferation, and apoptosis were analyzed by cell counting kit-8, 5-Ethynyl-2'-deoxyuridine and flow cytometry analysis. Oxidative stress was analyzed by evaluating the levels of Malondialdehyde (MDA) and Reactive Oxygen Species (ROS) and the activity of Superoxide Dismutase (SOD). The associations among circDLGAP4, miR-6085 and GDF11 were identified by dual-luciferase reporter, RNA immunoprecipitation (RIP) and RNA pull-down assays. Celastrol reduced OGD/R-induced inhibition of circDLGAP4 expression in HBMECs. Celastrol treatment protected HBMECs from OGD/R-induced cell proliferation inhibition and apoptosis and oxidative stress promotion; however, circDLGAP4 depletion attenuated these effects. CircDLGAP4 acted as a sponge for miR-6085, and miR-6085 mimics restored circDLGAP4-mediated effects in OGD/R-stimulated HBMECs. In addition, GDF11 was identified as a targte of miR-6085, and participated in the regulation of miR-6085 to OGD/R-induced HBMEC damage. Further, circDLGAP4 absence inhibited GDF11 expression by interacting with miR-6085 under Celastrol treatment. Celastrol ameliorated OGD/R-induced HBMEC apoptosis and oxidative stress by circDLGAP4/miR-6085/GDF11 pathway, supporting the use of Celastrol as a therapeutic agent for cerebral infarction.

Sub-chronic toxicity of an aqueous extract of Epimedium sagittatum (Sieb. Et Zucc.) Maxim. in rats.

Epimedium sagittatum (Sieb. et Zucc.) Maxim., a traditional medicinal plant in Asia, is widely used in clinical settings but its safety in vivo is unclear. This study investigated the sub-chronic toxicity of E. sagittatum aqueous extract to rats with a 13-week daily intragastric administration of 7.5, 15, or 30 g/kg. Nine constituents of the aqueous extract were identified by ultra-performance liquid chromatography (UPLC). Organ weights, organ coefficients, serum biochemistry parameters, histopathology, and metabolomic analysis were performed. In female rats, treatment increased the liver, thymus, and adrenal gland coefficients (p < 0.05). Liver, pancreas, and adrenal gland injury were observed. The levels of six metabolites were altered by the treatment (p < 0.05). In male rats, treatment altered liver, heart, and thymus coefficients (p < 0.05) and liver, adrenal gland, and heart injury were observed. The levels of 11 metabolites were altered (p < 0.05). The no-observed-adverse-effect level was not determined but would be below 7.5 g/kg in rats treated for 13 weeks. In female rats, E. sagittatum may injure the liver and pancreas and dysregulate the biosynthesis of phenylalanine, tyrosine, tryptophan, valine, leucine, and isoleucine and the metabolism of phenylalanine. In male rats, the extract may injure the liver and adrenal gland and dysregulate the biosynthesis of valine, leucine, and isoleucine and the metabolism of pyruvate.

Cardioprotective effects of gypenoside XVII against ischemia/reperfusion injury: Role of endoplasmic reticulum stress, autophagy, and mitochondrial fusion fission balance.

Gypenoside XVII (GP-17), a tetracyclic triterpene saponin isolated from the functional food Gynostemma pentaphyllum, has been demonstrated protective effects against cerebrovascular and cardiovascular diseases on multiple disease models. In this study, we established a myocardial infarction (MI) model by ligating the left anterior descending coronary artery, and explored whether GP-17 prevent myocardial ischemia/reperfusion (I/R) injuries in mice. Compared with the I/R group, GP-17 significantly improved the cardiac function, reduced the MI, decreased myocardial pathology, activated superoxide dismutase and catalase, and reduced the content of lactate dehydrogenase, creatine kinase, malondialdehyde, and inflammatory factor. The proteomic analysis showed multiple differential proteins between the GP-17 and I/R groups enriched in endoplasmic reticulum and mitochondria. Western-Blot showed that GP-17 significantly decreased the expression of GRP78, ATF6, CHOP, and phosphorylation of PERK, indicating the inhibition of ERS. GP-17 inhibited the expression of ATG5, LC3A/B, and BAX, illustrating the suppression of autophagy and apoptosis. Moreover, both GP-17 and 4-PBA could improve the downregulated Mfn2, meaning that inhibition of ERS regulated the mitochondrial fusion fission balance, thus protected the function of mitochondria. In conclusion, we found that GP-17 prevented against myocardial I/R injury by inhibit ERS-induced cell apoptosis, autophagy, oxidative stress, and mitochondrial division.

Psoralen induces liver injuries through endoplasmic reticulum stress signaling in female mice.

Psoralen is the main coumarin component of Fructus psoraleae. Previously, we have found that psoralen induced hepatocytes apoptosis via PERK and ATF6 related ER stress pathways in vitro. In this study, we investigated the toxicity and ER stress induced by psoralen in female C57 mice. Mice were fed with 80 mg/kg of psoralen intra-gastrically for either 3, 7, or 21 days. Liver and kidney were weighed and their coefficients were calculated. The serum was isolated to examine the biochemical parameters including alanine aminotransferase (ALT) activity, aspartate aminotransferase (AST) activity, alkaline phosphatase (ALP) activity, blood urea nitrogen (BUN), total bile acid (TBA), total bilirubin (TBIL), and creatinine (CRE). The transcription and expression of ER stress-related markers were determined by Wes-automated Protein Simple system, Western blot and RT-PCR. Psoralen administration for 3 days significantly increased liver coefficients but decreased kidney coefficients of mice. Histopathological examination showed minimal inflammatory cell foci and vacuolar degeneration in the liver. Besides, serum levels of ALT, TBA, BUN, and CRE were markedly altered by psoralen. Moreover, psoralen significantly increased expression and transcription levels of ER stress related markers, including Grp78, PERK, eIF2α, ATF4, IRE1α, ATF6, and XBP1. These results illustrated that psoralen induced liver injuries through ER stress signaling in female mice.

Human epididymis protein 4: a novel predictor of ischemic cardiomyopathy.

BACKGROUND: The prognostic value of human epididymis protein 4 (HE4) in patients with ischemic cardiomyopathy (ICM) is unknown. METHODS: A total of 103 patients with ICM were prospectively enrolled in this study from Hunan Provincial People's Hospital between February 2019 and June 2019. All patients were tested for HE4 levels at baseline and follow-up. Endpoints of the study included cardiovascular death and heart failure-related hospitalization. RESULTS: A total of 96 patients with ICM were included for analysis. After a mean follow-up period of 263 (153-313) days, cardiovascular events were observed in 45 patients. Serum HE4 levels in patients with events were significantly higher than those in patients without events [188.70 (113.35-326.82) pmol/L versus 92.90 (61.50-123.20) pmol/L, P < 0.001]. Multivariate Cox regression analysis revealed that HE4 [χ2: 9.602, hazard ratio (HR): 1.003, 95% confidence interval (CI): 1.001-1.005, P = 0.002] and age [χ2: 4.55, HR: 1.044, 95% CI: 1.003-1.085, P = 0.033] were independent predictors of events. After adjusting for age and sex, the risk of events in patients with HE4 > 100.2 pmol/L was higher than that in patients with HE4 ≤ 100.2 pmol/L [HR: 3.372, 95% CI: 1.409-8.065, P < 0.001]. CONCLUSION: HE4 is an independent predictor of cardiovascular death and heart failure-related rehospitalization in patients with ICM.

Profiling Aerosol Liquid Water Content Using a Polarization Lidar.

Aerosol liquid water content (ALWC) plays fundamental roles in atmospheric radiation and chemical processes. However, there is little information about ALWC vertical distribution due to the lack of sufficient measurement. In this study, a novel method to retrieve ALWC using a polarization lidar is proposed. By analyzing lidar measurement combined with in situ chemical composition measurements at the surface, the particle linear depolarization ratio δp is found to be well correlated with the liquid water mass fraction. The method is built upon a valid relationship between δp and the ratio of ALWC to the particle backscatter coefficient. ALWC can be retrieved with a relative error of 30% with this method. A case study shows that the ALWC in upper levels of the boundary layer may be different from that at the ground, suggesting the importance of measuring ALWC vertical profiles during haze episodes. The study proves that polarization lidars have the potential to retrieve vertical distributions of ALWC which will benefit studies on haze formation.

Simultaneous characterization of multiple Psoraleae Fructus bioactive compounds in rat plasma by ultra-high-performance liquid chromatography coupled with triple quadrupole mass spectrometry for application in sex-related differences in pharmacokinetics.

A method for the simultaneous quantification of 13 bioactive compounds (psoralen, isopsoralen, isobavachin, bakuchalcone, neobabaisoflavone, bavachin, corylin, psoralidin, isobavachalcone, bavachinin, corylifol A, bavachalcone, and bakuchiol) by ultra-high-performance liquid chromatography coupled with triple quadrupole mass spectrometry has been developed and validated in rat plasma. Osthol was used as an internal standard and plasma samples were pretreated with one-step liquid-liquid extraction. These analytes were separated using a gradient mobile phase system of water and acetonitrile at a flow rate of 0.2 mL/min on a reverse-phase C18 column and analyzed in the selected multiple reactions monitoring mode. All calibration curves were linear (r > 0.9952) over the tested ranges. The intra- and interday accuracy and precisions of these analytes at three different concentration levels were within the acceptable limits of <15% at all concentrations. The mean recoveries of these analytes at three concentrations were more than 60.2% and the matrix effects were in the range of 85-115%. Stability studies proved that the analytes were stable under the tested conditions. The developed method was applied to evaluating the pharmacokinetic study of 13 bioactive compounds after oral administration of Psoraleae Fructus in rat of different genders. Some active compounds in Psoraleae Fructus had sex-related pharmacokinetics.

Psoralen induces hepatic toxicity through PERK and ATF6 related ER stress pathways in HepG2 cells.

Psoralen has potential hepatotoxicity and has a certain promoting effect on the clinical liver injury of Psoralea corylifolia L (Fructus Psoraleae). This study investigated the underlying mechanisms of psoralen-induced hepatotoxicity in vitro. HepG2 cells were treated with psoralen for 6, 12, 24, or 48 h, and an endoplasmic reticulum (ER) stress-specific inhibitor, 4-PBA, was employed to investigate the mechanism of psoralen on ER stress and unfolded protein response (UPR). Cell viability was tested by MTT assay, ATP assay, and cell death by LDH. The apoptosis was reflected by the flow cytometry, caspase-8, and caspase-3 activates. The expression of ER stress-related markers was determined by RT-PCR and western blot. We found that psoralen significantly decreased cell viability, increased activities of caspase-8 and caspase-3, and upregulated expression of CHOP and BAX in a time- and dose-dependent manner. Moreover, psoralen significantly increased the expression and transcription levels of ER stress-related markers, including Grp78, PERK, eIF2α, ATF4, and ATF6, while IRE1α was not significantly affected. And 4-PBA could effectively inhibit psoralen-induced cell death and apoptosis along with the inhibition of ER stress responses. These results suggested that psoralen causes liver injury due to the induction of the ER stress-mediated apoptosis via PERK-eIF2α-ATF4-CHOP and ATF6-CHOP related pathways.

Evaluation of Anti-Inflammatory Activities of a Triterpene ß-Elemonic Acid in Frankincense In Vivo and In Vitro.

The purpose of this research was to extract and separate the compounds from frankincense, and then evaluate their anti-inflammatory effects. The isolated compound was a representative tetracyclic triterpenes of glycine structure according to ¹H-NMR and 13C-NMR spectra, which is ß-elemonic acid (ß-EA). We determined the content of six different localities of frankincense; the average content of ß-EA was 41.96 mg/g. The toxic effects of ß-EA administration (400, 200, 100 mg/kg) for four weeks in Kunming (KM) mice were observed. Compared with the control group, the body weight of mice, the visceral coefficients and serum indicators in the ß-EA groups showed no systematic variations. The anti-inflammatory effects of ß-EA were evaluated in LPS-induced RAW264.7 cells, xylene-induced induced ear inflammation in mice, carrageenin-induced paw edema in mice, and cotton pellet induced granuloma formation in rats. ß-EA inhibited overproduction of tumor necrosis factor-α(TNF-α), interleukin-6 (IL-6), monocyte chemotactic protein 1 (MCP-1), soluble TNF receptor 1 (sTNF R1), Eotaxin-2, Interleukin 10 (IL-10) and granulocyte colony-stimulating factor (GCSF) in the RAW264.7 cells. Intragastric administration with ß-EA (300, 200, and 100 mg/kg in mice, and 210, 140, and 70 mg/kg in rats) all produced distinct anti-inflammatory effects in vivo in a dose-dependent manner. Following treatment with ß-EA (300 mg/kg, i.g.), the NO level in mice ears and PGE2 in mice paws both decreased (p < 0.01). In conclusion, our study indicates that ß-EA could be a potential anti-inflammatory agent for the treatment of inflammatory diseases.

Salvianolic Acid A Protects H9c2 Cells from Arsenic Trioxide-Induced Injury via Inhibition of the MAPK Signaling Pathway.

BACKGROUND/AIMS: This study aimed to investigate whether Salvianolic acid A (Sal A) conferred cardiac protection against Arsenic trioxide (ATO)-induced cardiotoxicity in H9c2 cells by inhibiting MAPK pathways activation. METHODS: H9c2 cardiac cells were exposed to 10 µM ATO for 24 h to induce cytotoxicity. The cells were pretreated with Sal A for 4 h before exposure to ATO. Cell viability was determined utilizing the MTT assay. The percentage of apoptosis was measured by a FITC-Annexin V/PI apoptosis kit for flow cytometry. Mitochondrial membrane potential (∆Ψm) was detected by JC-1. The intracellular ROS levels were measured using an Image-iTTM LIVE Green Reactive Oxygen Species Detection Kit. The apoptosis-related proteins and the MAPK signaling pathways proteins expression were quantified by Western blotting. RESULTS: Sal A pretreatment increased cell viability, suppressed ATO-induced mitochondrial membrane depolarization, and significantly altered the apoptotic rate by enhancing endogenous antioxidative enzyme activity and ROS generation. Signal transduction studies indicated that Sal A suppressed the ATO-induced activation of the MAPK pathway. More importantly, JNK, ERK, and p38 inhibitors mimicked the cytoprotective activity of Sal A against ATO-induced injury in H9c2 cells by increasing cell viability, up-regulating Bcl-2 protein expression, and down-regulating both Bax and caspase-3 protein expression. CONCLUSION: Sal A decreases the ATO-induced apoptosis and necrosis of H9c2 cells, and the underlying mechanisms of this protective effect of Sal A may be connected with the MAPK pathways.

Association between platelet glycoprotein Ia C807T gene polymorphism and ischemic stroke: a meta-analysis in a separate ethnic group.

Many studies have been examined the association of platelet glycoprotein (GP) Ia C807T polymorphism with ischemic stroke (IS) susceptibility. However, the results of these studies are inconsistent. To further assess the effects of GP Ia C807T polymorphism on the risk of IS, a meta-analysis was performed in a separate ethnic group. Relevant studies were identified using PubMed and Chinese databases through January 2017. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the associations. Finally, 13 studies contained 2438 IS cases and 2308 controls included. In the total analyses, a significantly elevated risk of IS was associated with all variants of GP Ia C807T in the Chinese population (T vs C: OR = 1.24, 95% CI = 1.09-1.40; TT vs CC: OR = 1.59, 95% CI = 1.17-2.15; TT and CT combined vs CC: OR = 1.32, 95% CI = 1.09-1.59; TT vs CC and CT: OR = 1.35, 95% CI = 1.04-1.76). In the subgroup analyses stratified by ethnicity and geographic areas, it revealed the significant results in Chinese Han and in South China. This meta-analysis provides the evidence that GP Ia C807T polymorphism may contribute to the IS development in the Chinese population, especially in South China, and further studies in other ethic groups are required for definite conclusions.

Elatoside C protects against hypoxia/reoxygenation-induced apoptosis in H9c2 cardiomyocytes through the reduction of endoplasmic reticulum stress partially depending on STAT3 activation.

Endoplasmic reticulum (ER) stress-induced apoptosis has been suggested to contribute to myocardial ischemia-reperfusion (I/R) injury. Elatoside C is one of the major triterpenoid compounds isolated from Aralia elata that is known to be cardioprotective. However, its effects on I/R injury to cardiac myocytes have not been clarified. This study aimed to investigate the possible protective effect of Elatoside C against hypoxia/reoxygenation (H/R)-induced H9c2 cardiomyocyte injury and its underlying mechanisms. H9c2 cardiomyocytes were subjected to H/R in the presence of Elatoside C. Our results showed that Elatoside C (25 µM) treatment provided significant protection against H/R-induced cell death, as evidenced by improved cell viability, maintained mitochondrial membrane potential, diminished mitochondrial ROS, and reduced apoptotic cardiomyocytes (P < 0.05). These changes were associated with the inhibition of ER stress-associated apoptosis markers (GRP78, CHOP, Caspase-12 and JNK), as well as the increased phosphorylation of STAT3 and an increased Bcl2/Bax ratio. Moreover, these effects of Elatoside C were prevented by the STAT3 inhibitor Stattic. Taken together, these results suggested that Elatoside C can alleviate H/R-induced cardiomyocyte apoptosis most likely by activating the STAT3 pathways and reducing ER stress-associated apoptosis.

[Current Status of Self-transcendence among Lung Cancer Patients 
and Its Influencing Factors].

BACKGROUND: Different degrees of self-transcendence exist in lung cancer patients, which can stimulate patients' self-awareness and promote them to face negative events in life positively, thus improving patients' quality of life and treatment outcomes. However, there are few reports on self-transcendence in lung cancer patients in China, and the related influencing factors have not yet been clarified. This study aims to investigate the current situation of self-transcendence in lung cancer patients and explore its risk factors, so as to provide a theoretical basis for clinical intervention decision-making. METHODS: 243 lung cancer patients who were admitted to the Department of Lung Cancer Center of West China Hospital, Sichuan University from September 2023 to February 2024 were enrolled as the study subjects; general information questionnaire, self-transcendence scale, Herth hope scale and social support scale were used for the investigation. The influencing factors related to self-transcendence of lung cancer patients were analyzed. RESULTS: The total mean score of self-transcendence in lung cancer patients was (44.73±8.94); the total mean score of hope level was (37.60±4.98), and the total mean score of social support was (41.31±7.27). Self-transcendence was positively correlated with hope level and social support (P<0.001, P<0.001). Education, hope level and social support were influencing factors of self-transcendence in lung cancer patients (P<0.05, P<0.001, P<0.05). CONCLUSIONS: Self-transcendence in lung cancer patients was at a low level and was influenced by hope level and social support. Healthcare professionals should pay attention to improving the hope level of lung cancer patients, carrying out targeted psychological interventions, and at the same time guiding them to enhance the perception of social support, so as to promote the realization of self-transcendence in patients.

Aqueous extract of Epimedium sagittatum (Sieb. et Zucc.) Maxim. induces liver injury in mice via pyroptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Epimedium sagittatum (Sieb. et Zucc.) Maxim. has been used traditionally in Asia. It can dispel wind and cold, tonify the kidney, and strengthen bones and tendons. However, adverse effects of E. sagittatum have been reported, and the underlying mechanisms remain unclear. AIM OF THE STUDY: This study aimed to investigate liver injury caused by an aqueous extract of E. sagittatum in Institute of Cancer Research (ICR) mice and explore its potential mechanisms. MATERIALS AND METHODS: Dried E. sagittatum leaves were decocted in water to prepare aqueous extracts for ultra-high performance liquid chromatography analysis. Mice were administered an aqueous extract of E. sagittatum equivalent to either 3 g raw E. sagittatum/kg or 10 g raw E. sagittatum/kg once daily via intragastric injection for three months. The liver weights and levels of the serum biochemical parameters including alanine transaminase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), total bilirubin (TBIL), and alkaline phosphatase were measured. Hematoxylin-eosin staining was performed for histopathology. Apoptosis was detected using the TUNEL apoptosis assay kit. IL-1ß was detected using ELISA kits. Proteomics was used to identify the differentially expressed proteins. Western blot analysis was performed to determine the levels of proteins significantly affected by the aqueous extract of E. sagittatum. RESULTS: E. sagittatum treatment increased the liver weights and liver coefficients, and ALT and AST levels significantly increased (p < 0.05). A high dose of E. sagittatum significantly increased LDH and TBIL levels (p < 0.05). Ruptured cell membranes and multiple sites of inflammatory cell infiltration were also observed. No evidence of apoptosis was observed. IL-1ß levels were significantly increased (p < 0.05). The expressions of PIK3R1, p-MAP2K4, p-Jun N-terminal kinase (JNK)/JNK, p-c-Jun, VDAC2, Bax, and CYC were upregulated, whereas that of Bcl-2 was inhibited by E. sagittatum. The expression of cleaved caspase-1 was significantly increased; however, its effects on GSDMD and GSDMD-N were significantly decreased. The expression levels of cleaved caspase-3 and its effector proteins GSDME and GSDME-N significantly increased. CONCLUSIONS: Our results suggest that the aqueous extract of E. sagittatum induces liver injury in ICR mice after three months of intragastric injection via inflammatory pyroptosis.

Gypenoside XVII attenuates renal ischemia-reperfusion injury by inhibiting endoplasmic reticulum stress and NLRP3 inflammasome-triggered pyroptosis.

BACKGROUND: Renal ischemia-reperfusion (I/R) is one of the main causes of acute kidney injury (AKI), for which there is currently no effective treatment. Recently, the interaction between endoplasmic reticulum (ER) stress and pyroptosis during AKI has been investigated. AIM: The purpose of this study was to investigate the protective effects of Gypenoside XVII (GP-17) against I/R-induced renal injury. METHODS: In this study, mice were divided into 6 groups, sham group, I/R group, GP-17 low-, medium-, high-dose group, and positive control 4-PBA group. The renal I/R was performed in mice by clamping the bilateral renal pedicles for 40 min, and then reperfusing for 24 h. Blood and kidney samples were collected for analysis. RESULTS: The results showed that GP-17 improved renal function and alleviated renal histopathological abnormalities caused by I/R. In addition, GP-17 pretreatment significantly decreased the expression or phosphorylation of ER stress response proteins including BIP, p-PERK, and CHOP. Besides, GP-17 inhibited the expression of pyroptosis proteins including caspase-1, GSDMD, and apoptotic protein BAX. The inflammatory factor IL-1ß in these GP-17 pretreatment groups was also significantly reduced. CONCLUSION: GP-17 blocked NLRP3 inflammasome activation by inhibiting ERS, thereby inhibiting renal tubular cell pyroptosis and apoptosis, and prevented renal I/R injury.

Untargeted metabolomics analysis of Gannan navel orange at different storage periods under room temperature using HS-SPME-GC-MS and UPLC-Q-TOF/MS.

Navel orange remains metabolized continuously during postharvest storage, but few studies have monitored the changes of these metabolites. Therefore, HS-SPME-GC-MS and UPLC-Q-TOF/MS were used to comprehensively investigate the dynamic changes of the components of Gannan navel orange during storage at room temperature. A total of 62 volatile components and 68 non-volatile components were identified. Principal Component Analysis and Partial Least Squares Discriminant Analysis showed that navel orange under different storage periods were clearly distinguished. Combined with VIP > 1 and p < 0.05, 19 volatile and 27 non-volatile differential metabolites were obtained. KEGG enrichment analysis revealed that flavonoid biosynthesis (map00941) was the primary metabolic pathway. The middle storage period had a higher antioxidant enzyme activity, but the malondialdehyde content was the opposite. These results reveal the changes of postharvest components of Gannan navel orange, providing a theoretical basis for the storage and product development of navel orange.

4-Phenylbutyric acid suppresses psoralen-induced hepatotoxicity by inhibiting ERS and reestablishing mitochondrial fusion-fission balance in mice.

Psoralen is a main active molecule of the traditional Chinese herb medicine Fructus Psoraleae. Our previous studies have shown that psoralen induced liver injury through the endoplasmic reticulum stress (ERS) signaling pathways. In this article, we studied whether the ERS inhibitor, 4-phenylbutyrate acid (4-PBA) could inhibit the liver toxicity caused by psoralen, and explored the underlying mechanisms. Mice were given the solvent, 20mg/kg, 40mg/kg, 80mg/kg of psoralen, or 80mg/kg of psoralen plus 4-PBA for 14 days. We found that 4-PBA significantly reduced the serum LDH and liver tissue MDA level, increased the activities of SOD and CAT, reduced liver weight and coefficient, repaired histopathological damage, and inhibited hepatocytes apoptosis induced by psoralen. RNA-seq transcriptomics found that except for the endoplasmic reticulum, the mitochondria was severely affected by psoralen. And genes involved in mitochondrial fusion, apoptosis, protein folding, and autophagy were found differently expressed in the psoralen group. Further studies found that 4-PBA inhibited the overexpression of GRP78 and CHOP, increased the Bcl-2/Bax ratio, and reduced the expression of Caspase-3. Moreover, 4-PBA reduced the overexpression of mitochondrial fission protein DRP1, increased the expression of fusion proteins Mfn-2 and OPA1, but has no inhibitory effects on autophagy proteins Atg5 or LC3A/B. In conclusion, 4-PBA inhibited ERS and reestablished mitochondrial fusion-fission balance, thereby blocking cell apoptosis, oxidative stress, and mitochondrial dysfunction, thus prevented against psoralen-induced hepatotoxicity.

Global research hotspots and trends in exercise interventions for rheumatoid arthritis over the past two decades: A bibliometric and visualization study.

Rheumatoid arthritis (RA) is a prolonged multifactorial autoimmune disease of unknown etiology. With the global population aging, the incidence of RA is increasing, highlighting the need for more effective treatments. Exercise interventions have been recognized as safe and effective for managing pain, improving function, and reducing fatigue in RA patients. However, the existing literature in this field lacks a thorough, organized, and clear line of analysis. In this study, we conducted a comprehensive analysis of the 20-year literature on exercise interventions for RA, aiming to identify hotspots and cutting-edge trends. Our objective is to provide subsequent researchers with valuable ideas and references. Using Cite Space, VOS viewer, and R-bibliometrix software for visualization and analysis, we compiled the main dataset from the web of science database, consisting of 1790 articles on exercise interventions in RA published between 2000 and 2023. Among these articles, the United States contributed the highest number of papers (433), while Karolinska Institutet ranked first institutionally with 90 papers. The study focused on the keyword's quality of life, cardiovascular disease, aerobic exercise, social support, psychology, and multidisciplinary care. The research highlighted the importance of clinical efficacy studies that investigate different types of exercise modalities (cardiorespiratory aerobic, resistance, aquatic, and neurological) either alone or in combination, to improve pain and function and reduce cardiovascular disease risk in patients with RA. Additionally, sedentary behavior, fatigue, and multidisciplinary care were identified as potential areas for further research. Overall, this study provides a scientific perspective on exercise interventions for RA and offers valuable insights for academics, funding organizations, and policymakers.

Effects of lumbar-pelvic training combined with electroacupuncture on chronic nonspecific low back pain.

This observational study was conducted to investigate the effect of lumbar-pelvic training (LP) combined with electroacupuncture (EA) in the treatment of chronic nonspecific low back pain. One hundred and twenty patients diagnosed with chronic nonspecific low back pain were evenly randomized to receive the following 4 treatments for 2 weeks: LP combined with EA (Group A), EA (Group B), LP (Group C) or no intervention (Group D). The LP was a self-developed training program containing 5 movements and was conducted three times a week to build up the strength of abdomen muscle groups. Four acupoints along the foot-taiyang bladder meridian and the governor vessel were chosen for EA five times a week based on the theory of Traditional Chinese Medicine. The Visual Analog Scale and Oswestry Disability Index were measured before and after treatment to assess the reduction of pain intensity and functional disability, respectively. Following the treatments, Visual Analog Scale and Oswestry Disability Index scores in all 3 intervention groups were significantly lower than those in the Group D without intervention (P < .01). Among the intervention groups, Group A's scores were lower than those of Group B or Group C (P < .01). The overall efficacy of Group A was 93.33%, which was higher than that of Group B (76.67%) and Group C (70.00%) (P < .01). In conclusion, this study suggest that our self-developed lumbar-pelvic training combined with electroacupuncture is effective for chronic nonspecific low back pain in terms of pain and disability reduction.

Exploring Effects and Mechanism of Ingredients of Herba Epimedii on Osteogenesis and Osteoclastogenesis In Vitro.

BACKGROUND: Herba Epimedii, a commonly used traditional herb, has been proven effective in ameliorating osteoporosis. However, the active ingredients and potential mechanism need further exploration. OBJECTIVE: To screen active ingredients of Herba Epimedii with the effect of ameliorating osteoporosis and to explore their potential mechanisms. METHODS: TCMSP and Swiss Target Prediction were applied to collect the ingredients of Herba Epimedii and their targets. UniProt, GeneCards, TTD, DisGeNET, and OMIM were adopted to search osteoporosis-related genes. STRING and DAVID were used to perform enrichment analysis. Effects of screened ingredients were evaluated on MC3T3-E1 cells and RAW264.7 cells, respectively. RESULTS: Eleven ingredients were screened by Network Pharmacology. They exerted a promoting effect on MC3T3-E1 cells (10-9-10-5 M). The ingredients didn't significantly affect ALP activity and osteoblastogenesis-related genes. Baohuoside 1, Sagittatoside B, Chlorogenic acid, Cryptochlorogenic acid, and Neochlorogenic acid significantly increased calcium depositions. The ingredients didn't exhibit a dose-dependent inhibition or promotion on RAW264.7 cells. Baohuoside 1, Sagittatoside B, Neochlorogenic acid, Cryptochlorogenic acid, Icariin, Epimedin A, Chlorogenic acid, Sagittatoside A, and Epimedin C suppressed the level of TRACP. Baohuoside 1, Sagittatoside B, Cryptochlorogenic acid, Neochlorogenic acid, Chlorogenic acid, Sagittatoside A, and Icariin decreased the number of multinucleated osteoclastic cells. Baohuoside 1, Sagittatoside B, and Cryptochlorogenic acid could significantly inhibit MMP-9 expression. CONCLUSION: Neochlorogenic acid, Sagittatoside B, Chlorogenic acid, and Cryptochlorogenic acid promoted MC3T3-E1 differentiation, among which Neochlorogenic acid showed significant promotion in viability, mineralization, and OPN expression. Baohuoside 1, Sagittatoside B, Cryptochlorogenic acid, Neochlorogenic acid, Chlorogenic acid, and Icariin inhibited RAW264.7 differentiation, among which Baohuoside 1 showed significant inhibition on TRACP, multinucleated osteoclastic cells number and MPP-9 expression. The mechanism might relate to the FoxO signaling pathway, MAPK signaling pathway, and TNF signaling pathway.