Development and validation of the patient-reported outcome for older people living with HIV/AIDS in China (PROHIV-OLD).

BACKGROUND: The involvement of quality of life as the UNAIDS fourth 90 target to monitor the global HIV response highlighted the development of patient-reported outcome (PRO) measures to help address the holistic needs of people living with HIV/AIDS (PLWHA) beyond viral suppression. This study developed and tested preliminary measurement properties of a new patient-reported outcome (PROHIV-OLD) measure designed specifically to capture influences of HIV on patients aged 50 and older in China. METHODS: Ninety-three older people living with HIV/AIDS (PLWHA) were interviewed to solicit items and two rounds of patient cognitive interviews were conducted to modify the content and wording of the initial items. A validation study was then conducted to refine the initial instrument and evaluate measurement properties. Patients were recruited between February 2021 and November 2021, and followed six months later after the first investigation. Classical test theory (CTT) and item response theory (IRT) were used to select items using the baseline data. The follow-up data were used to evaluate the measurement properties of the final instrument. RESULTS: A total of 600 patients were recruited at the baseline. Of the 485 patients who completed the follow-up investigation, 483 were included in the validation sample. The final scale of PROHIV-OLD contained 25 items describing five dimensions (physical symptoms, mental status, illness perception, family relationship, and treatment). All the PROHIV-OLD dimensions had satisfactory reliability with Cronbach's alpha coefficient, McDonald's ω, and composite reliability of each dimension being all higher than 0.85. Most dimensions met the test-retest reliability standard except for the physical symptoms dimension (ICC = 0.64). Confirmatory factor analysis supported the structural validity of the final scale, and the model fit index satisfied the criterion. The correlations between dimensions of PROHIV-OLD and MOS-HIV met hypotheses in general. Significant differences on scores of the PROHIV-OLD were found between demographic and clinical subgroups, supporting known-groups validity. CONCLUSIONS: The PROHIV-OLD was found to have good feasibility, reliability and validity for evaluating health outcome of Chinese older PLWHA. Other measurement properties such as responsiveness and interpretability will be further examined.

Online preconcentration and determination of five alkaloids in Yangxinshi tablet by large-volume sample stacking and micelle to solvent stacking in cyclodextrin-modified electrokinetic chromatography.

The two-step preconcentration technique consisting of large-volume sample stacking (LVSS) and micelle to solvent stacking (MSS) in cyclodextrin-modified electrokinetic chromatography (CDEKC) was developed for the analysis of five cationic alkaloids in complex Chinese herbal prescriptions. Relevant parameters affecting separation and stacking performance were optimized separately. Under the optimal LVSS-MSS-CDEKC conditions, less analysis time and organic solvent were required, and the enhancement factors of analytes ranged from 12 to 15 compared with the normal CDEKC separation mode. Further, all validation results demonstrated good applicability and multiple alkaloids (epiberberine, dehydrocorydaline, jatrorrhizine, coptisine and berberine) in Yangxinshi tablet (YXST) have been simultaneously determined. This approach presents powerful potential for the determination of multiple components in complex preparations of Chinese medicine.

Eugenol Possesses Colitis Protective Effects: Impacts on the TLR4/MyD88/NF-[Formula: see text]B Pathway, Intestinal Epithelial Barrier, and Macrophage Polarization.

Eugenol (EU) has been shown to ameliorate experimental colitis due to its anti-oxidant and anti-inflammatory bioactivities. In this study, DSS-induced acute colitis was established and applied to clarify the regulation efficacy of EU on intestinal barrier impairment and macrophage polarization imbalance along with the inflammatory response. Besides, the adjusting effect of EU on macrophages was further investigated in vitro. The results confirmed that EU intervention alleviated DSS-induced colitis through methods such as restraining weight loss and colonic shortening and decreasing DAI scores. Microscopic observation manifested that EU maintained the intestinal barrier integrity in line with the mucus barrier and tight junction protection. Furthermore, EU intervention significantly suppressed the activation of TLR4/MyD88/NF-[Formula: see text]B signaling pathways and pro-inflammatory cytokines gene expressions, while enhancing the expressions of anti-inflammatory cytokines. Simultaneously, WB and FCM analyses of the CD86 and CD206 showed that EU could regulate the DSS-induced macrophage polarization imbalance. Overall, our data further elucidated the mechanism of EU's defensive effect on experimental colitis, which is relevant to the protective efficacy of intestinal barriers, inhibition of oxidative stress and excessive inflammatory response, and reprogramming of macrophage polarization. Hence, this study may facilitate a better understanding of the protective action of the EU against UC.

Deciphering the molecular mechanism of Bu Yang Huan Wu Decoction in interference with diabetic pulmonary fibrosis via regulating oxidative stress and lipid metabolism disorder.

BACKGROUND: Diabetes mellitus type 2 and pulmonary fibrosis have been found to be closely related in clinical practice. Diabetic pulmonary fibrosis (DPF) is a complication of diabetes mellitus, but its treatment has yet to be thoroughly investigated. Bu Yang Huan Wu Decoction (BYHWD) is a well-known traditional Chinese prescription that has shown great efficacy in treating pulmonary fibrosis with hypoglycemic and hypolipidemic effects. METHODS: The active ingredients of BYHWD and the corresponding targets were retrieved from the Traditional Chinese Medicine Systematic Pharmacology Database (TCMSP) and SymMap2. Disease-related targets were obtained from the GeneCard, OMIM and CTD databases. GO enrichment and KEGG pathway enrichment were carried out using the DAVID database. AutoDock Vina software was employed to perform molecular docking. Molecular dynamics simulations of proteinligand complexes were conducted by Gromacs. Animal experiments were further performed to validate the effects of BYHWD on the selected core targets, markers of oxidative stress, serum lipids, blood glucose and pulmonary fibrosis. RESULTS: A total of 84 active ingredients and 830 target genes were screened in BYHWD, among which 56 target genes intersected with DPF-related targets. Network pharmacological analysis revealed that the active ingredients can regulate target genes such as IL-6, TNF-α, VEGFA and CASP3, mainly through AGE-RAGE signaling pathway, HIF-1 signaling pathway and TNF signaling pathway. Molecular docking and molecular dynamics simulations suggested that IL6-astragaloside IV, IL6-baicalein, TNFα-astragaloside IV, and TNFα-baicalein docking complexes could bind stably. Animal experiments showed that BYHWD could reduce the expression of core targets such as VEGFA, CASP3, IL-6 and TNF-α. In addition, BYHWD could reduce blood glucose, lipid, and MDA levels in DPF while increasing the activities of SOD, CAT and GSH-Px. BYHWD attenuated the expression of HYP and collagen I, mitigating pathological damage and collagen deposition within lung tissue. CONCLUSIONS: BYHWD modulates lipid metabolism disorders and oxidative stress by targeting the core targets of IL6, TNF-α, VEGFA and CASP3 through the AGE-RAGE signaling pathway, making it a potential therapy for DPF.

Combination of large-volume sample stacking with polarity switching and micelle electrokinetic chromatography for the analysis of anion compounds in Yangxinshi tablets.

INTRODUCTION: Yangxinshi tablet (YXST) is a traditional Chinese medicine preparation characterized by its high efficacy and safety for the treatment of cardiovascular diseases. Anionic compounds have been revealed as potential active components. However, there is currently limited research regarding its quality control. OBJECTIVE: We aimed to establish a strategy for the simultaneous separation and determination of five key anionic compounds in YXST. METHOD: A sensitive and efficient analytical method was developed and applied for the simultaneous separation and determination of five key compounds in YXST using large-volume sample stacking with polarity switching and micelle electrokinetic chromatography (LVSS-PS-MEKC) coupled with diode array detection. Crucial parameters, including sample volume, applied voltage, composition and pH of the running buffer, concentration of organic modifier, and switching time of the polarity, were systematically evaluated and optimized using a single variable method to enhance separation performance. Furthermore, the impact of cyclodextrin and sodium dodecyl sulfate as electrolyte modifiers was also investigated. RESULTS: Under the optimal conditions, baseline separation of the five compounds (daidzein, puerarin, glycyrrhiztinic acid, chlorogenic acid, and salvianolic acid B) was achieved within 20 min. In comparison to the conventional MEKC mode, the constructed LVSS-PS-MEKC method exhibited a more than sixfold increase in the enrichment factor. The method was validated in terms of linearity, precision, accuracy, 24 h stability, and recovery and successfully applied to analyze YXST samples. CONCLUSION: A sensitive strategy was developed for the simultaneous separation and determination of five key anionic components in YXST, offering a robust and efficient strategy for pharmaceutical analysis.

Wuling capsule modulates macrophage polarization by inhibiting the TLR4-NF-κB signaling pathway to relieve liver fibrosis.

BACKGROUND AND PURPOSE: Wuling capsule (WL) has good efficacy in the clinical treatment of chronic hepatitis B and liver injury. Liver fibrosis is a common pathological feature of chronic liver disease and may progress to irreversible cirrhosis and liver cancer. Accumulating evidence reveals that modulating macrophage polarization contribute to the therapy of liver fibrosis. However, the effects of WL on modulating macrophage polarization to relive liver fibrosis remain unclear. This study investigated the anti-liver fibrosis effects of WL in carbon tetrachloride (CCl4)-induced liver fibrosis in rats, and the modulation effects and underlying molecular mechanism on macrophage polarization. METHODS: A rat liver fibrosis model was constructed by intraperitoneal injection of 40 % CCl4 olive oil mixture. At 2, 4, 6, and 8 weeks, the histopathological status of the liver was assessed by hematoxylin-eosin (HE) and Masson staining; the liver biochemical indexes were measured in rat liver tissue. The expression levels of inflammatory cytokines in liver tissue were detected by ELISA. The mRNA levels and proteins expression of macrophage markers of different phenotypes, TLR4-NF-κB signaling pathway indicators were detected independently by ELISA, immunofluorescence, RT-PCR and western blotting. RESULTS: In vivo, WL treatment attenuated abnormal changes in weight, organ indices and biochemical indices, alleviated pathological changes, and reduced collagen fiber deposition as well as the expression of α-SMA in liver tissues. Further studies revealed that WL decreased the expression of the macrophage M1 polarization markers inducible nitric oxide synthase (iNOS), TNF-α, IL-6, and CD86, promoted the expression of the M2 macrophage polarization markers IL-10, CD206, and arginase-1 (Arg-1), and inhibited the activation of the TLR4-NF-κB signaling pathway via several key signaling proteins. In vitro, WL significantly suppressed macrophage M1 polarization, and promoted M2 polarization while boosted M1 polarization transform to M2 polarization in LPS-activated RAW264.7 cells. CONCLUSIONS: This study demonstrated that WL modulated macrophage polarization against liver fibrosis mainly by inhibiting the activation of the TLR4-NF-κB signaling pathway.

Maternal folic acid and vitamin B12 supplementation during medium to late gestation promotes fetal development via improving placental antioxidant capacity, angiogenesis and amino acid transport.

BACKGROUND: Folic acid and vitamin B12 (FV), being B vitamins, not only facilitate the remethylation of homocysteine (Hcy) but also contribute to embryonic development. This study aimed to assess the impact of FV supplementation during late pregnancy on sows' reproductive performance, amino acid metabolism, placental angiogenesis, and related parameters. Twenty primiparous sows at day 60 of gestation were randomly allocated to two groups: a basal diet (CON) group and a group receiving a basal diet supplemented with folic acid at 20 ppm and vitamin B12 at 125 ppb. RESULTS: The findings revealed that dietary FV supplementation significantly reduced the incidence of intrauterine growth retardation compared to the CON group (P < 0.05). Furthermore, it led to a decrease in the Hcy levels in umbilical cord serum (P < 0.05) and activation of the placental mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway (P < 0.05). Additionally, FV supplementation lowered placental malondialdehyde levels (P < 0.05) and increased the expression of placental thioredoxin (P = 0.05). Moreover, maternal FV supplementation notably elevated placental vascular density (P < 0.05) and the expression of sodium-coupled neutral amino acid transporter 2 (SNAT2) (P < 0.05), as well as amino acid concentrations in umbilical cord blood (P < 0.05). CONCLUSION: Maternal FV supplementation during medium to late gestation reduced Hcy levels in umbilical cord blood and positively impacted fetal development. This improvement was closely associated with increased placental antioxidant capacity and vascular density, as well as activation of the placental mTORC1-SNAT2 signaling pathway. © 2023 Society of Chemical Industry.

[Mechanism of Wuling Capsules against hepatic fibrosis based on network pharmacology and animal experiments].

The present study aimed to explore the underlying mechanism of Wuling Capsules in the treatment of hepatic fibrosis(HF) through network pharmacology, molecular docking, and animal experiments. Firstly, the chemical components and targets of Wuling Capsules against HF were searched from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), Traditional Chinese Medicines Integrated Database(TCMID), GeneCards, and literature retrieval. The protein-protein interaction(PPI) network analysis was carried out on the common targets by STRING database and Cytoscape 3.9.1 software, and the core targets were screened, followed by Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses. Enrichment analysis was conducted on the core targets and the "drug-core component-target-pathway-disease" network was further constructed. Subsequently, molecular docking between core components and core targets was conducted using AutoDock Vina software to predict the underlying mechanism of action against HF. Finally, an HF model induced by CCl_4 was constructed in rats, and the general signs and liver tissue morphology were observed. HE and Masson staining were used to analyze the liver tissue sections. The effects of Wuling Capsules on the levels of inflammatory factors, hydroxyproline(HYP) levels, and core targets were analyzed by ELISA, RT-PCR, etc. A total of 445 chemical components of Wuling Capsules were screened, corresponding to 3 882 potential targets, intersecting with 1 240 targets of HF, and 47 core targets such as TNF, IL6, INS, and PIK3CA were screened. GO and KEGG enrichment analysis showed that the core targets mainly affected the process of cell stimulation response and metabolic regulation, involving cancer, PI3K-Akt, MAPK, and other signaling pathways. Molecular docking showed that the core components of Wuling Capsules, such as lucidenic acid K, ganoderic acid B, lucidenic acid N, saikosaponin Q2, and neocryptotanshinone, had high affinities with the core targets, such as TNF, IL6 and PIK3CA. Animal experiments showed that Wuling Capsules could reduce fat vacuole, inflammatory infiltration, and collagen deposition in rat liver, decrease the levels of inflammatory cytokines TNF-α, IL-6, and HYP, and downregulated the expressions of PI3K and Akt mRNA. This study suggests that the anti-HF effect of Wuling Capsules may be achieved by regulating the PI3K-Akt signaling pathway, reducing the levels of TNF-α and IL-6 inflammatory factors, and inhibiting the excessive deposition of collagen.

Chinese Medicine Enhancing Response Rates to Immunosuppressant PD-L1 Inhibitor and Improving the Quality of Life of Hepatocellular Carcinoma-Bearing Mice.

Background: Malignant tumors are a significant disease endangering human health. Chinese Medicine (CM) plays an important role in comprehensive and holistic tumor treatment. Objectives: We aimed to investigate whether CM combined with the immunosuppressant PD-1/PD-L1 inhibitor has a good synergistic effect and can significantly improve response rates for the immunosuppressant. Methods: We combined CM with immunosuppressant in treating six-week-old hepatocellular carcinoma-bearing mice and compared the outcomes of groups undergoing different interventions: blank group, control group, CM group, PD-L1 inhibitor group, and CM + PD-L1 inhibitor group, with ten mice in each group. The quality of life was evaluated along with the tumor inhibition effects and growth rates. Results: CM significantly reduced tumor load and improved the quality of life of cancer-bearing mice. The survival rate was 81.8% in the control group, 100% in the CM group, 90.9% in the PD-L1 inhibitor group, and 100% in the combined group in the first week. The survival rate was 45.5% in the control group, 54.5% in the CM group, 81.8% in the PD-L1 inhibitor group, and 81.8% in the combined group in the second week. 38% mice in the CM+PD-L1 inhibitor group with smaller tumor size than the average of the control group, which was much higher than other treatment groups. CM also reduced the expression of JAK2 mRNA and STAT3 mRNA, although not significantly (P > 0.05), and reduced PD-L1 mRNA in tumor tissue compared to the control group (P < 0.05). Conclusions: CM had a synergistic effect on PD-L1 inhibitors and increased response rates to PD-L1 inhibitor treatment.

Coptis chinensis and Berberine Ameliorate Chronic Ulcerative Colitis: An Integrated Microbiome-Metabolomics Study.

Coptis chinensis Franch (RC), has historically been used for the treatment of "Xiao Ke" and "Xia Li" symptoms in China. "Xia Li" is characterized by abdominal pain and diarrhea, which are similar to the clinical symptoms of ulcerative colitis (UC). For the first time, this study aims to compare the anti-colitis effects of berberine (BBR) and total RC alkaloids (TRCA) and investigate the underlying metabolites and gut microbiota biomarkers. Metabolomics results showed that several colitis-related biomarkers, including lysophosphatidyl ethanolamine, lysophosphatidylcholine, scopolamine-methyl-bromide, N1-methyl-2-pyridone-5-carboxamide, 4-hydroxyretinoic acid, and malic acid, were significantly improved in model mice after BBR and TRCA treatments. High-dose BBR and TRCA treatments reversed the mouse colon shortening caused by dextran sodium sulfate (DSS), alleviated bowel wall swelling, and reduced inflammatory cell infiltration. BBR and TRCA restored the damaged mucosa integrity in colitis mice by upregulating claudin 1 and occludin, preventing colon epithelium apoptosis by inhibiting the cleavage of caspase 3. Additionally, BBR and TRCA significantly decreased the richness of the pathogenic bacteria Bacteroides acidifaciens but increased the abundance of the probiotic Lactobacillus spp. Notably, TRCA exhibited superior anti-colitis effects to those of BBR. Thus, this agent warrants further study and application in the treatment of inflammatory bowel disease in the clinic.

Effects of single and combined contamination of total petroleum hydrocarbons and heavy metals on soil microecosystems: Insights into bacterial diversity, assembly, and ecological function.

Deciphering the impact of single and combined contamination of total petroleum hydrocarbons (TPH) and heavy metals on soil microecosystems is essential for the remediation of contaminated habitats, yet it remains incompletely understood. In this study, we employed high-throughput sequencing to investigate the impact of single TPH contamination, single metal contamination, and their co-contamination on soil microbial diversity, assembly mechanisms, composition, ecological function, and resistome. Our results revealed that contamination led to a reduction in alpha diversity, with single contamination displaying lower diversity compared to co-contamination, depending on the concentration of pollutants. Community beta diversity was primarily driven by turnover rather than nestedness, and narrower ecological niches were detected under pollution conditions. The neutral community model suggested that homogenizing dispersal played a significant role in the community assembly process under single TPH or co-contamination, while homogeneous selection dominated under heavy metals pollution. Procrustes analysis demonstrated a correlation between community composition and functional divergence, while Mantel tests linked this divergence to concentrations of Cr, Cr6+, Pb, and TPH. Interestingly, soils co-polluted with TPH and heavy metals exhibited similar genera, community functions, and resistomes as soils contaminated with only metals, highlighting the significant impact of heavy metals. Ecological functions related to carbon (C), nitrogen (N), and sulfur (S) cycles were enhanced under TPH pollution but impaired under heavy metals stress. These findings enhance our understanding of soil microecosystems subjected to TPH, heavy metals, and their co-contamination, and carry significant implications for environmental microecology and pollutant risk assessment.

Modulation of HIV-1 capsid multimerization by sennoside A and sennoside B via interaction with the NTD/CTD interface in capsid hexamer.

Small molecules that bind to the pocket targeted by a peptide, termed capsid assembly inhibitor (CAI), have shown antiviral effects with unique mechanisms of action. We report the discovery of two natural compounds, sennoside A (SA) and sennoside B (SB), derived from medicinal plants that bind to this pocket in the C-terminal domain of capsid (CA CTD). Both SA and SB were identified via a drug-screening campaign that utilized a time-resolved fluorescence resonance energy transfer assay. They inhibited the HIV-1 CA CTD/CAI interaction at sub-micromolar concentrations of 0.18 µM and 0.08 µM, respectively. Mutation of key residues (including Tyr 169, Leu 211, Asn 183, and Glu 187) in the CA CTD decreased their binding affinity to the CA monomer, from 1.35-fold to 4.17-fold. Furthermore, both compounds induced CA assembly in vitro and bound directly to the CA hexamer, suggesting that they interact with CA beyond the CA CTD. Molecular docking showed that both compounds were bound to the N-terminal domain (NTD)/CTD interface between adjacent protomers within the CA hexamer. SA established a hydrogen-bonding network with residues N57, V59, Q63, K70, and N74 of CA1-NTD and Q179 of CA2-CTD. SB formed hydrogen bonds with the N53, N70, and N74 residues of CA1-NTD, and the A177and Q179 residues of CA2-CTD. Both compounds, acting as glue, can bring αH4 in the NTD and αH9 in the CTD of the NTD/CTD interface close to each other. Collectively, our research indicates that SA and SB, which enhance CA assembly, could serve as novel chemical tools to identify agents that modulate HIV-1 CA assembly. These natural compounds may potentially lead to the development of new antiviral therapies with unique mechanisms of action.

A global profiling strategy for identification of the total constituents in Chinese herbal medicine based on online comprehensive two-dimensional liquid chromatography-quadrupole time-of-flight mass spectrometry combined with intelligentized chemical classification guidance.

A comprehensive strategy for effective identification of total constituents in Chinese patent medicine has been advanced applying full scan-preferred parent ions capture-static and active exclusion (FS-PIC-SAE) acquisition coupled with intelligent deep-learning supported mass defect filter (MDF) process, with Naoxintong capsule (NXT) as a case. Online comprehensive two-dimensional liquid chromatography (2DLC) coupled with Q-TOF-MS/MS system was established for obtaining the excellent separation and detection performance of total components, which could exhibit excellent peak capacity with 1052 and orthogonality with 0.69. In addition, a total of 901 unknown compounds could be classified into nine chemical classes rapidly and effectively, based on the intelligent deep-learning algorithm supported MDF model with 96.4% accuracy. Consequently, 276 compounds were successfully identified from NXT, especially including 44 flavonoids, 27 phenolic acids, 25 fatty acids, 17 saponins, 21 phthalocyanines, 20 triterpenes, 10 monoterpenes, 13 diterpenoid ketones, 14 amino acids, and others. It is concluded that the proposed program is an effective and practical strategy enabling the in-depth chemical profiling of complex herbal and biological samples.

Anti-rheumatoid arthritis effects of total saponins from Rhizoma Panacis Majoris on adjuvant-induced arthritis in rats and rheumatoid arthritis fibroblast-like synoviocytes.

BACKGROUND: Total saponins from Rhizoma Panacis Majoris (RPMTG) showed significant antitumour activity in our previous studies. Rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) with tumour-like characteristics have received attention as a therapeutic target for RA. However, the potential effect and mechanism of action of RPMTG against RA-FLS remain unclear. OBJECTIVE: The study investigated the therapeutic effect of RPMTG on adjuvant-induced arthritis (AIA) in rats, and the regulation effect and underlying mechanism on apoptosis, autophagy of RA-FLS. METHODS: The therapeutic effect of RPMTG was determined by the symptoms and signs of AIA rats. The production of inflammatory cytokines was detected by ELISA. Histopathological change of the ankle and synovial tissues were detected by HE staining. Flow cytometry, Hoechst 33342/PI staining, MDC staining, and TEM were used to determine the effects of RPMTG on apoptosis and autophagy. Western blotting was applied to detect the expression levels of proteins. RESULTS: In AIA rats, RPMTG treatment ameliorated paw swelling, and arthritis score, restored synovial histopathological changes, inhibited the expression of IL-6 and IL-1ß, exhibiting its potent anti-arthritis effect. In vitro, RPMTG depressed the proliferation of RA-FLS, arrested cell cycle in G0/G1 phase, and induced mitochondria-mediated apoptosis. Moreover, RPMTG significantly inhibited the autophagy in vivo and in vitro, proved by decreasing the expression of autophagy-related indicators (LC3II/LC3I, Beclin-1). Mechanistically, the study demonstrated that the activation of p38 MAPK and PI3K/Akt/mTOR pathways was mainly involved in the therapeutic effects of RPMTG. Interestingly, the effect of RPMTG on apoptosis was reversed after Rapamycin treatment, which preliminarily demonstrated that the inhibitory effect of RPMTG on autophagy was beneficial to the effect on inducing apoptosis. The regulation effect of RPMTG concurrently on apoptosis and autophagy revealed its unique advantages in RA treatment. CONCLUSION: RPMTG showed potent therapeutic effects on AIA rats and induced apoptosis, inhibited autophagy mainly through activating the p38 MAPK and PI3K/Akt/mTOR pathways in RA-FLS.

Simultaneous Separation and Determination of Nine Active Ingredients in Sanyetangzhiqing by Cyclodextrin-Modified Micellar Electrokinetic Capillary Electrophoresis-Diode Array Detector.

A simple and sensitive strategy using cyclodextrin-modified micellar electrokinetic chromatography with diode array detector was developed and applied for the simultaneous separation and determination of nine components in Sanyetangzhiqing (SYTZQ), a hypoglycemic and hypolipidemic agent. Several important parameters affecting separation performance were evaluated and optimized using single variable methods. Under the optimal conditions, baseline separation of the nine components, including four flavonoids (hyperoside, isoquercitrin, quercetin-3-O-glucuronoside, and astragalin), four phenolic acids (chlorogenic acid, rosmarinic acid, salvianolic acid B, and lithospermic acid), and a monoterpenoids (paeoniflorin), were achieved in less than 16 min. The correlation coefficients of the calibration curves were over 0.9996 for all the analytes. Intraday and interday precisions ranged from 0.4% to 4.8% and 1.7% to 5.0%, respectively. Recoveries of analytes varied from 95.3% to 105%. Validation results as well as the application to analyse SYTZQ samples demonstrated the applicability of the proposed method and thus provided an effective tool for the quality control of SYTZQ. Moreover, with the advantages of short time consuming, low energy consumption, high efficiency, and low cost, this method has laid a foundation for the determination and quality evaluation of multicomponents in Chinese herbal compounds.

The Role of Complementary and Alternative Medicine on Cancer-Related Fatigue in Adults: An Overview of Systematic Reviews.

BACKGROUND: Cancer-related fatigue (CRF) has an enormous adverse impact on quality of life and subsequent therapy of cancer patients. Complementary and alternative medicine (CAM) is reported to improve CRF in many systematic reviews (SRs), but the effects are controversial because of variations in the quality and outcomes. METHODS: Thirteen databases were searched from inception to September 2022. Only SRs of randomized controlled trials (RCTs) were included. We assessed the quality of included SRs with the AMSTAR-2 tool, the strength of evidence with the GRADE system, the risk of bias with the ROBIS tool, and the integrity of SRs with the PRISMA checklist. RESULTS: We included 30 eligible SRs (27 meta-analyses). Based on the AMSTAR-2 tool, 29 SRs were rated as "critically low" quality, and only one was rated as "low" quality. With the ROBIS tool, 19 SRs demonstrated a low risk of bias. According to the PRISMA checklist, no SRs reported all the items, and 10 SRs sufficiently reported over 70%. Based on the GRADE system, 7 outcomes were assessed as high-quality evidence. CONCLUSION: This overview demonstrates promising evidence for the effectiveness of CAM interventions in the treatment of CRF in adults. The roles of qigong, music, auricular point therapy, and dietary supplements in CRF need further evaluation. Although findings are mixed, it is recommend to select appropriate CAM to manage cancer-related fatigue under the guidance of physicians. More studies with rigorous methodological designs and sufficient sample sizes are needed.

In-capillary screening and quantifying the antioxidants of Yangxinshi Tablet using field-enhanced sample injection-micellar electrokinetic chromatography.

An in-capillary 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulphonate) as oxyradicals combining field-enhanced sample injection with micellar electrokinetic chromatography was developed for screening and determination of the major antioxidants in Yangxinshi Tablet. To obtain simultaneous separation and detection of radicals and analytes, relevant factors were optimized separately. Under the optimum conditions, four compounds including salvianolic acid B, hyperoside, puerarin, and caffeic acid were identified as the major antioxidants. All validation results covering recovery, precision, and stability demonstrated good applicability of the method. On this basis, the total antioxidant activity was successfully evaluated in terms of the decreased peak area of radicals. There was a correlation coefficient of 0.8974 between the total contents of major antioxidants and the total antioxidative activity of the sample. Therefore, these four compounds were selected as combinatorial markers for the quality evaluation of Yangxinshi Tablet. It was concluded that the established method presented a powerful potential to screen and quantify active ingredients in the complex preparation of Chinese medicine.

Single-cell RNA sequencing reveals that VIM and IFITM3 are vital targets of Dengzhan Shengmai capsule to protect against cerebral ischemic injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Ischemic stroke is one of the leading causes of mortality, but therapies are limited. Dengzhan Shengmai capsule (DZSM) was included by the Chinese Pharmacopoeia 2020 and has been broadly used for the treatment of ischemic stroke. However, the mechanism of DZSM against ischemic stroke is unclear. AIM OF THE STUDY: This study used RNA sequencing (RNA-seq) and single-cell RNA sequencing (scRNA-seq) to investigate the mechanism of action of DZSM against ischemic stroke. MATERIALS AND METHODS: The rats were randomly divided into six groups: the Sham, I/R (water), I/R + DZSM-L (0.1134g/kg), I/R + DZSM-H (0.4536g/kg), I/R + NMDP (20mg/kg), and I/R + Ginaton (20mg/kg). The rats were administrated drugs for 5 days then followed by the ischemic brain injury caused by middle cerebral artery occlusion (MCAO). The neuroprotective effect was assessed by infraction rate, neurological deficit scores, regional cerebral blood flow (rCBF), hematoxylin and eosin (H&E) staining, and Nissl staining. Based on RNA-seq and scRNA-seq, the vital biological processes and core targets of DZSM against cerebral ischemia were revealed. Enzyme-linked immunosorbent assay (ELISA) and immunofluorescence (IF) staining were used to investigate the vital biological processes and core targets of DZSM against ischemic stroke. RESULTS: Administration of DZSM significantly reduced the infarction rate and Zea Longa score, Garcia JH score, and ameliorated the reduction in rCBF. And alleviated the neuronal damage, such as increased neuronal density level and Nissl bodies density level. RNA-seq analysis revealed that DZSM played important roles in inflammation and apoptosis. ELISA and IF straining validation confirmed that DZSM significantly decreased the expression of IL-6, IL-1ß, TNF-α, ICAM-1, IBA-1, MMP9, and Cleaved caspase-3 in MCAO rats. ScRNA-seq analysis identified 8 core targets in neurons including HSPB1, SPP1, MT2A, GFAP, IFITM3, VIM, CRIP1, and GPD1, and VIM and IFITM3 was verified to be decreased by DZSM in neurons. CONCLUSION: Our study illustrates the neuroprotective effect of DZSM against ischemia stroke, and VIM and IFITM3 were identified as vital targets in neurons of DZSM in protecting against MCAO-induced I/R injury.

[Effects of electroacupuncture pretreatment on NLRP3 inflammasome in mice with ventilator-induced lung injury].

OBJECTIVE: To observe the effect of electroacupuncture (EA) pretreatment on inflammatory response in ven-tilator-induced lung injury (VILI) mice, so as to explore the underlying mechanism of EA pretreatment on prevention of VILI. METHODS: C57BL/6 mice were randomly divided into sham-operation group, model group, EA group and sham-acupoint group，with 8 mice in each group. The VILI model was established by ventilation with high tidal volume. Mice in the EA group and sham-acupoint group were given EA at "Zusanli" (ST36)and "Feishu"(BL13) or non-acupoints (located at 1-2 cm on both sides of the tail root of the proximal trunk) before mechanical ventilation, 30 min each time, once a day for 5 days. Arterial blood was collec-ted for blood gas analysis, the total protein content in bronchoalveolar lavage fluid (BALF) was detected by BCA method. The contents of interleukin-1ß (IL-1ß) and interleukin-18 (IL-18) in BALF were detected by ELISA. Lung injury score was determined after HE staining. The protein expression levels of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3), apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC) and Caspase-1 in lung tissue was detected by Western blot. RESULTS: Compared with the sham-operation group, the arterial partial pressure of oxygen and oxygenation index were decreased(P<0.05), the levels of total protein, IL-1ß and IL-18 in BALF, the W/D value and the pathological injury score of lung tissue and the protein expression levels of NLRP3, Caspase-1 and ASC were increased(P<0.05)in the model group. Following the interventions, the above mentioned increased or decreased indicators were reversed(P<0.05) in the EA group rather than in the sham-acupoint group. CONCLUSION: EA pretreatment of ST36 and BL13 can reduce the damage of lung tissue caused by mechanical ventilation, which may be related to its effect in reducing the expression of NLPR3 inflammasome related proteins, reducing the activation of inflammasome, and thereby reducing the inflammatory response.

YY1 (Yin-Yang 1), a transcription factor regulating systemic inflammation, is involved in cognitive impairment of depression.

AIM: Clinical and preclinical studies suggest that alterations in the peripheral and brain immune system are associated with the pathophysiology of depression, also leading to changes in local glucose metabolism in the brain. Here, the authors identified Yin-Yang 1 (YY1), a transcription factor closely associated with central and peripheral inflammation. METHODS: Plasma levels of YY1, interleukin (IL) 6, and IL-1ß in major depressive disorder (MDD) were collected before and after treatment with vortioxetine, and correlation with clinical and cognitive scores was studied. Chronic unpredictable mild stress was treated with vortioxetine. Micropositron emission tomography (microPET) was used to analyze glucose metabolism and mRNA, and the protein level of the YY1-nuclear factor κB (NF-κB)-IL-1ß inflammatory pathway were measured in related brain regions. RESULTS: Plasma levels of YY1 and IL-1ß were significantly increased in MDD and decreased after treatment with vortioxetine. Meanwhile, the level of YY1 in plasma was negatively correlated with cognitive functions in patients with MDD and positively correlated with the level of IL-1ß in plasma. Compared with the control group, in chronic unpredictable mild stress rats, (microPET) analysis showed that the decrease of glucose metabolism in the hippocampus, entorhinal cortex, amygdala, striatum, and medial prefrontal cortex was reversed after treatment. mRNA and protein level of related molecular in YY1-NF-κB-IL-1ß inflammatory pathway decreased in the hippocampus and was reversed by vortioxetine. CONCLUSION: The current study suggests that the YY1-NF-κB-IL-1ß inflammatory pathway may play an essential role in both mood changes and cognitive impairment in depression, and may be associated with changes in glucose metabolism in emotion regulation and cognition. These findings provide new evidence for the inflammatory mechanisms of depression.