The Complications of Corticosteroid for Patients with Community-acquired Pneumonia: A Systematic Review and Meta-Analysis.

Background: Many randomized controlled trials (RCTs) have reported the complications of corticosteroids for patients with community-acquired pneumonia with inconsistent results. An explicit systematic review and meta-analysis were conducted in this study to evaluate the complications of corticosteroids for patients with community-acquired pneumonia. Methods: Using PubMed, Embase, the Global Index Medicus of the World Health Organization (WHO), the WHO clinical trial registry, and Clinicaltrials.gov, a thorough literature search of RCTs was carried out. Inclusion criteria included RCTs comparing the use of any kind of a specified corticosteroid with the placebo control group. The complications were analyzed, including gastrointestinal (GI) bleeding, healthcare-associated infection (HAI), acute kidney injury (AKI), hospital readmission, hyperglycemia, neuropsychiatric complications, and adverse cardiac events. Results: The result can be concluded that the risk of gastrointestinal (GI) bleeding, healthcare-associated infection (HAI), acute kidney injury (AKI), hospital readmission, neuropsychiatric complications, and adverse cardiac events between the intervention and control groups were not significantly different. However, corticosteroids can increase the risk of hyperglycemia as compared to the control group who did not receive corticosteroids (RR= 1.72, 95 % CI: 1.38-2.14, P < .01). In the subgroup analysis, the meta-analysis showed a significant difference in the risk of hyperglycemia between the prednisolone and control groups (RR= 1.81, 95 % CI: 1.29-2.54, P < .01). There is no heterogeneity between studies (I2= 0%). The subgroup difference was not significant (P = .11). Conclusions: Through our analysis, the use of corticosteroids can increase the risk of hyperglycemia for patients with community-acquired pneumonia. Further studies are required to be conducted to confirm the findings due to limited clinical trials.

Moxibustion-mediated alleviation of synovitis in rats with rheumatoid arthritis through the regulation of NLRP3 inflammasome by modulating neutrophil extracellular traps.

Purpose: This study investigates the potential mechanism of moxibustion in the treatment of rheumatoid arthritis (RA) by regulating the neutrophil extracellular trap (NET)/NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome axis with the use of a rat model with adjuvant arthritis (AA). Methods: Four groups, including normal control (NC), AA, moxibustion (MOX), and chlor-amidine (Cl-amidine) were created from 24 Wistar male rats (6 rats/group). After the intervention and treatment respectively, the joint swelling degree (JSD) and arthritis index (AI) were compared. The pathological changes of synovium were observed with hematoxylin and eosin staining and transmission electron microscopy. The formation of NETs in synovial tissues was detected with immunofluorescence staining. The protein expression of myeloperoxidase (MPO), neutrophil elastase (NE), citrullinated histone (Cit-H3), acyl arginine deiminase 4 (PAD-4), and NLRP3 was measured in the synovium of rat ankle joints with western blotting, and the levels of anti-cyclic citrullinated peptide antibody (CCP-Ab) and interleukin (IL)-1ß were examined in rat serum with ELISA. Results: AA modeling markedly increased JSD, AI, synovial protein expression of MPO, NE, Cit-H3, PAD-4, and NLRP3, and serum levels of CCP-Ab and IL-1ß in rats (P < 0.01). JSD and AI, as well as the levels of MPO, NE, Cit-H3, PAD-4, NLRP3, CCP-Ab, and IL-1ß, were significantly lowered in AA rats by MOX and Cl-amidine (P < 0.01). In addition, AA modeling caused severe pathological injury in the synovium of rats, which was annulled by MOX and Cl-amidine. The formation of NETs in synovium was substantially promoted in rats by AA modeling and was significantly reduced in AA rats after the treatment. Conclusion: Moxibustion can markedly alleviate synovitis and repress inflammatory factor release in AA rats, which may be achieved by diminished synthesis of NETs or their constituents and the blocked formation of NLRP3 inflammasome.

Robust Artificial Intelligence Tool for Atrial Fibrillation Diagnosis: Novel Development Approach Incorporating Both Atrial Electrograms and Surface ECG and Evaluation by Head-to-Head Comparison With Hospital-Based Physician ECG Readers.

BACKGROUND: Atrial fibrillation (AF) increases risk of embolic stroke, and in postoperative patients, increases cost of care. Consequently, ECG screening for AF in high-risk patients is important but labor-intensive. Artificial intelligence (AI) may reduce AF detection workload, but AI development presents challenges. METHODS AND RESULTS: We used a novel approach to AI development for AF detection using both surface ECG recordings and atrial epicardial electrograms obtained in postoperative cardiac patients. Atrial electrograms were used only to facilitate establishing true AF for AI development; this permitted the establishment of an AI-based tool for subsequent AF detection using ECG records alone. A total of 5 million 30-second epochs from 329 patients were annotated as AF or non-AF by expert ECG readers for AI training and validation, while 5 million 30-second epochs from 330 different patients were used for AI testing. AI performance was assessed at the epoch level as well as AF burden at the patient level. AI achieved an area under the receiver operating characteristic curve of 0.932 on validation and 0.953 on testing. At the epoch level, testing results showed means of AF detection sensitivity, specificity, negative predictive value, positive predictive value, and F1 (harmonic mean of positive predictive value and sensitivity) as 0.970, 0.814, 0.976, 0.776, and 0.862, respectively, while the intraclass correlation coefficient for AF burden detection was 0.952. At the patient level, AF burden sensitivity and positive predictivity were 96.2% and 94.5%, respectively. CONCLUSIONS: Use of both atrial electrograms and surface ECG permitted development of a robust AI-based approach to postoperative AF recognition and AF burden assessment. This novel tool may enhance detection and management of AF, particularly in patients following operative cardiac surgery.

Danlou Recipe promotes cholesterol efflux in macrophages RAW264.7 and reverses cholesterol transport in mice with hyperlipidemia induced by P407.

INTRODUCTION: Liver X Receptor (LXR) agonists could attenuate the development of atherosclerosis but bring excess lipid accumulation in the liver. Danlou Recipe was believed to be a benefit for improving the lipid profile. Thus, it is unclear whether Danlou Recipe could attenuate hyperlipidemia without excess lipid accumulated in the liver of mice. This study aimed to clarify if Danlou Recipe could alleviate the progression of hyperlipidemia in mice without extra lipids accumulated in the liver. METHODS: Male murine macrophage RAW264.7 cells and murine peritoneal macrophages were used for the in vitro experiments. Cellular cholesterol efflux was determined using the fluorescent cholesterol labeling method. Those genes involved in lipid metabolism were evaluated by qRT-PCR and western blotting respectively. In vivo, a mouse model of hyperlipidemia induced by P407 was used to figure out the effect of Danlou Recipe on reverse cholesterol transport (RCT) and hyperlipidemia. Ethanol extract of Danlou tablet (EEDL) was prepared by extracting the whole powder of Danlou Prescription from ethanol, and the chemical composition was analyzed by ultra-performance liquid chromatography (UPLC). RESULTS: EEDL inhibits the formation of RAW264.7 macrophage-derived foam cells, and promotes ABCA1/apoA1 conducted cholesterol efflux in RAW264.7 macrophages and mouse peritoneal macrophages. In the P407-induced hyperlipidemia mouse model, oral administration of EEDL can promote RCT in vivo and improve fatty liver induced by a high-fat diet. Consistent with the findings in vitro, EEDL promotes RCT by upregulating the LXR activities. CONCLUSION: Our results demonstrate that EEDL has the potential for targeting RCT/LXR in the treatment of lipid metabolism disorders to be developed as a safe and effective therapy.

Peripheral Blood Inflammatory Cytokine Factors Expressions are Associated with Response to Acupuncture Therapy in Postpartum Depression Patients.

Background: Increasing evidences demonstrate that immune dysregulation can result in depression, and it is reported that persistent inflammatory response is related to the unresponsiveness of antidepressant treatment. Purpose: This study aimed to explore the reason why some responded but some not responded to acupuncture in treating postpartum depression (PPD), and whether it related to the levels of inflammatory cytokines. Patients and Methods: Women diagnosed with PPD were recruited in to accept 8-week acupuncture. All subjects were assessed the 17-item Hamilton Depression Rating Scale (HDRS17) at baseline, week 1, week 2, week 4 and week 8 during the treatment. A panel of 9 cytokines was measured at baseline and 8 weeks. Results: Of the 121 participants, 96 completed the 8-week assessment and 46 completed the blood sample collection. HDRS17 scores of 96 subjects showed significant statistical reduction since the first week (P = 0.002) and reached to 5.31 (P < 0.000) at the end of therapy. And we divided the 46 subjects into responders and non-responders according to the response rate of HDRS17 scores. Responders and non-responders did not differ significantly between-group in changes in the 9 cytokines. In responders, IL-6, IL-10 and IFN-γ levels were statistically lower (P = 0.006; P = 0.033; P = 0.024), while TGF-ß1 was statistically higher after 8 weeks treatment (P < 0.000). In non-responders, the levels of IL-5, TNF-α and TGF-ß1 were statistically higher (P = 0.018; P < 0.000; P < 0.000), while IFN-γ was statistically lower (P = 0.005). Conclusion: Acupuncture could alleviate depressive symptoms of patients with PPD and might through adjusting peripheral inflammatory response by up-regulating anti-inflammatory cytokines and down-regulating pro-inflammatory cytokines.

Biogenic Selenium Nanoparticles Synthesized with Alginate Oligosaccharides Alleviate Heat Stress-Induced Oxidative Damage to Organs in Broilers through Activating Nrf2-Mediated Anti-Oxidation and Anti-Ferroptosis Pathways.

Selenium (Se) is an essential trace element for maintaining health due to its ideal antioxidant properties. We previously prepared a new type of biogenic selenium nanoparticles based on alginate oligosaccharides (SeNPs-AOS), and this study aimed to investigate the protective effects of SeNPs-AOS (Se particle size = 80 nm, Se content = 8%) on organ health in broilers challenged with HS. A total of 192 21-day-old Arbor Acres broilers were randomly divided into four groups according to a 2 × 2 experimental design, including a thermoneutral zone group (TN, raised under 23 ± 1.5 °C); TN + SeNPs-AOS group (TN group supplemented 5 mg/kg SeNPS-AOS); HS group (HS, raised under 33 ± 2 °C for 10 h/day); and HS + SeNPs-AOS group (HS group supplemented 5 mg/kg SeNPS-AOS). There were six replicates in each group (eight broilers per replicate). The results showed that SeNPs-AOS improved the splenic histomorphology, enhanced the activity of catalase (CAT) and glutathione peroxidase (GSH-Px) of the spleen, as well as upregulating the splenic mRNA expression of antioxidant-related genes in broilers under HS. In addition, SeNPs-AOS reversed the pathological changes in bursa caused by HS increased the activity of GST, GSH-Px, and CAT and upregulated the mRNA expression of Nrf2 and antioxidant-related genes in the bursa of heat-stressed broilers. In addition, dietary SeNPs-AOS improved the hepatic damage, increased the activity of GSH-Px in the liver, and upregulated the mRNA expression of antioxidant-related genes while downregulating the Keap1 gene expression of the liver in broilers during HS. Moreover, dietary SeNPs-AOS upregulated the anti-ferroptosis-related genes expression of liver in broilers under HS. In conclusion, dietary SeNPs-AOS could relieve HS-induced oxidative damage to the spleen, bursa of Fabricius and liver in broilers by upregulating the Nrf2-mediated antioxidant gene expression and SeNPs-AOS could also upregulate the expression of hepatic Nrf2-related anti-ferroptosis genes in heat-stressed broilers. These findings are beneficial for the development of new nano-antioxidants in broilers.

Moxibustion intervention improves synovitis by down-regulating NLRP3/Caspase-1/IL-1ß signaling of synovial tissue in rats with adjuvant arthritis. / 基于NLRP3/Caspase-1/IL-1ßä¿¡å·é€šè·¯æŽ¢è®¨è‰¾ç¸æ”¹å–„ä½å‰‚æ€§å ³èŠ‚ç‚Žå¤§é¼ æ»‘è†œç‚Žçš„æœºåˆ¶.

OBJECTIVES: To observe the effect of moxibustion on activities of NOD-like receptor family protein 3 (NLRP3)/cysteine aspartic acid specific protease-1 (Caspase-1)/interleukin-1ß (IL-1ß) signaling pathway in rats with adjuvant arthritis (AA), so as to explore its mechanisms underlying improvement of rheumatoid arthritis (RA). Me-thods Thirty male Wistar rats were randomly divided into normal control, AA model and moxibustion groups, with 10 rats in each group. The AA model was replicated by raising in wind, cold and damp environment combined with complete Freund's adjuvant injection. In the moxibustion group, moxibustion was applied to bilateral "Shenshu" (BL23) and "Zusanli"(ST36) for 20 min each time, once daily for 21 days. Changes of joint swelling degree (JSD) and arthritis index (AI) in each group were observed. The ultrastructural changes of synovial cells in each group were observed by transmission electron microscopy. The protein expression levels of NLRP3, apoptosis-associated speck-like protein (ASC), Caspase-1, tumor necrosis factor-α (TNF-α) and IL-1ß in the synovial tissues of the knee joint were measured by Western blot. RESULTS: Compared with the normal control group, JSD, AI and the protein expressions of NLRP3, ASC, Caspase-1, TNF-α and IL-1ß in the synovial tissues were significantly increased (P<0.01) in the model group. In comparison with the model group, JSD, AI and the protein expression levels of NLRP3, ASC, Caspase-1, TNF-α and IL-1ß were significantly decreased (P<0.01) in the moxibustion group. Results of transmission electron microscope showed an irregular and vague nuclear membrane of synovial cells, and unclear mitochondrial membrane boundary with sparse, swelling crests in the model group, which was relatively milder in the damage degree in the moxibustion group. CONCLUSIONS: Moxibustion can relieve the inflammatory response in the synovial membrane of AA rats, which may be related to its function in down-regulating synovial NLRP3/Caspase-1/IL-1ß inflammatory signaling.

Effect of auricular acupressure combined with acupuncture for juvenile pseudomyopia.

This retrospective study investigated the effect of auricular acupressure combined with acupuncture for juvenile pseudomyopia (JPM). In this retrospective study, we collected and analyzed a total of 66 eligible records of subjects with JPM. They were allocated into a treatment group (n = 33) and a control group (n = 33). All participants in both groups received auricular acupressure. Additionally, children in the treatment group also underwent acupuncture. The primary outcome was naked visual acuity (VA). It was performed using a standard E visual acuity chart. The secondary outcome was visual fatigue symptoms, as assessed by the College of Optometrists in Vision Development Quality of Life (COVD-QoL) questionnaire. All outcomes were analyzed before and after treatment. There were no significant differences regarding the naked VA and COVD-QoL scores before and after treatment between the 2 groups. However, there were significant differences regarding on naked VA (P < .01) and COVD-QoL scores (P < .01) within 2 groups compared before and after treatment. The findings of this study showed that both APP plus acupuncture and APP alone benefit children with JPM.

Discovery and evaluation of active compounds from Xuanfei Baidu formula against COVID-19 via SARS-CoV-2 Mpro.

BACKGROUND: The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2) is still a widespread concern. As one of the effective traditional Chinese medicine (TCM) formulae, Xuanfei Baidu formula (XFBD) shows significant efficacy for treatment of COVID-19 patients. However, its antiviral active compounds and mechanism are still unclear. PURPOSE: In this study, we explored the bioactive compounds of XFBD and its antiviral mechanism by integrating computational analysis and experimental testing. METHODS: Focusing on the SARS-CoV-2 main protease (Mpro), as a key target in virus transcription and replication, the fluorescence resonance energy transfer (FRET) assay was built to screen out satisfactory natural inhibitors in XFBD. The surface plasmon resonance (SPR) and isothermal titration calorimetry (ITC) were undertaken to verify the binding affinity of ligand-Mpro. Omicron BA.1.1 and BA.2.3 variants were used to evaluate the antiviral activity of the focused compounds in non-cytotoxicity concentrations. For introducing the molecular mechanism, computational modeling and NMR spectra were employed to characterize the ligand-binding modes and identify the ligand-binding site on Mpro. RESULTS: From a library of 83 natural compounds, acteoside, licochalcone B, licochalcone D, linoleic acid, and physcion showed the satisfactory inhibition effects on Mpro with IC50 ranging from 1.93 to 42.96 µM, which were further verified by SPR. Showing the excellent binding affinity, acteoside was witnessed to gain valuable insights into the thermodynamic signatures by ITC and presented antiviral activity on Omicron BA.1.1 and BA.2.3 variants in vitro. The results revealed that acteoside inhibited Mpro via forming the hydrogen bond between 7-H of acteoside and Mpro. CONCLUSION: Acteoside is regarded as a representative active natural compound in XFBD to inhibit replication of SARS-CoV-2, which provides the antiviral evidence and some insights into the identification of SARS-CoV-2 Mpro natural inhibitors.

[Moxibustion combined with western medication for rheumatoid arthritis with blood stasis obstruction and its effect on platelet activation].

OBJECTIVE: To investigate the clinical efficacy and action mechanism of moxibustion combined with western medication for rheumatoid arthritis (RA) with blood stasis obstruction. METHODS: Fifty-six patients of RA with blood stasis obstruction were randomly divided into an observation group and a control group, with 28 patients in each group. The patients in the control group were treated with oral administration of leflunomide tablets and celecoxib capsules, while the patients in the observation group were treated with moxibustion in addition to the treatment used in the control group. Moxibustion was performed at bilateral Zusanli (ST 36), Shenshu (BL 23), Xuehai (SP 10), and ashi points, once every other day, three times a week. The treatment duration for both groups was 12 weeks. The TCM syndrome score, disease activity score-28 (DAS-28), rheumatoid factor (RF), hypersensitive C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), hemorheological indexes (whole blood viscosity high shear, whole blood viscosity low shear, plasma viscosity), serum calcium ion (Ca2+) level, and platelet count (PLT) were observed before and after treatment, and the clinical efficacy was evaluated after treatment in the two groups. RESULTS: Compared with those before treatment, the TCM syndrome scores, DAS-28 scores, RF, hs-CRP, ESR, whole blood viscosity high shear, whole blood viscosity low shear, plasma viscosity, and PLT were decreased after treatment in both groups (P<0.01), with the observation group showing lower values compared with those in the control group (P<0.05). Compared with those before treatment, the serum Ca2+ levels were increased after treatment in both groups (P<0.01), and the observation group showed a higher increase than that in the control group (P<0.05). The total effective rate was 85.7% (24/28) in the observation group, which was higher than 67.9% (19/28) in the control group (P<0.05). CONCLUSION: Moxibustion combined with western medication could alleviate clinical symptoms in patients with RA of blood stasis obstruction, and its mechanism may be related to the inhibition of platelet activation.

The chemical profiling of Salvia plebeia during different growth periods and the biosynthesis of its main flavonoids ingredients.

Salvia plebeia (Lamiaceae) is a valuable medicinal plant widely distributed across Asia and Oceania. However, the composition and accumulation patterns of its active ingredients in different organs during the growth and their biosynthetic mechanism remain unknown. Therefore, we conducted metabolite profiling, transcriptomic analysis, and biological functional verification to explore the distribution, accumulation, and biosynthesis mechanisms of flavonoids in S. plebeia. We identified 70 metabolites including 46 flavonoids, 16 phenolic acids, seven terpenoids, and one organic acid, of which 21 were previously unreported in S. plebeia. Combining metabolomic-transcriptomic analysis and biological functional verification, we identified the key genes involved in biosynthesis of its main active ingredients, hispidulin and homoplantaginin, including SpPAL, SpC4H, Sp4CL2, Sp4CL5, SpCHS1, SpCHI, SpFNS, SpF6H1, SpF6OMT1, SpF6OMT2, SpUGT1, SpUGT2, and SpUGT3. Using the identified genes, we reconstructed the hispidulin and homoplantaginin biosynthesis pathways in Escherichia coli, and obtained a yield of 5.33 and 3.86 mg/L for hispidulin and homoplantaginin, respectively. Our findings provide valuable insights into the changes in chemical components in different organs of S. plebeia during different growth and harvest stages and establishes a foundation for identifying and synthesizing its active components.

Characterization of a mouse-adapted strain of bat severe acute respiratory syndrome-related coronavirus.

Bats carry genetically diverse severe acute respiratory syndrome-related coronaviruses (SARSr-CoVs). Some of them utilize human angiotensin-converting enzyme 2 (hACE2) as a receptor and cannot efficiently replicate in wild-type mice. Our previous study demonstrated that the bat SARSr-CoV rRsSHC014S induces respiratory infection and lung damage in hACE2 transgenic mice but not wild-type mice. In this study, we generated a mouse-adapted strain of rRsSHC014S, which we named SMA1901, by serial passaging of wild-type virus in BALB/c mice. SMA1901 showed increased infectivity in mouse lungs and induced interstitial lung pneumonia in both young and aged mice after intranasal inoculation. Genome sequencing revealed mutations in not only the spike protein but the whole genome, which may be responsible for the enhanced pathogenicity of SMA1901 in wild-type BALB/c mice. SMA1901 induced age-related mortality similar to that observed in SARS and COVID-19. Drug testing using antibodies and antiviral molecules indicated that this mouse-adapted virus strain can be used to test prophylactic and therapeutic drug candidates against SARSr-CoVs. IMPORTANCE The genetic diversity of SARSr-CoVs in wildlife and their potential risk of cross-species infection highlights the importance of developing a powerful animal model to evaluate the antibodies and antiviral drugs. We acquired the mouse-adapted strain of a bat-origin coronavirus named SMA1901 by natural serial passaging of rRsSHC014S in BALB/c mice. The SMA1901 infection caused interstitial pneumonia and inflammatory immune responses in both young and aged BALB/c mice after intranasal inoculation. Our model exhibited age-related mortality similar to SARS and COVID-19. Therefore, our model will be of high value for investigating the pathogenesis of bat SARSr-CoVs and could serve as a prospective test platform for prophylactic and therapeutic candidates.

Mume Fructus (Prunus mume Sieb. et Zucc.) extract accelerates colonic mucosal healing of mice with colitis induced by dextran sulfate sodium through potentiation of cPLA2-mediated lysophosphatidylcholine synthesis.

BACKGROUND: Mume Fructus (MF) is the fruit of Prunus mume Sieb. et Zucc, a plant of Rosaceae family. Previous studies demonstrated that MF was capable of ameliorating ulcerative colitis (UC) in mice, its action mechanism needs to be clarified. PURPOSE: This study deciphered whether and how MF extract accelerates colonic mucosal healing, the therapeutic endpoint of UC. METHODS: Biochemical, histopathological and qRT-PCR analyses were utilized to define the therapeutic efficacy of MF on dextran sulfate sodium (DSS)-induced colitis in mice. UHPLC-QTOF-MS/MS-based metabolomics technique was adopted to explore the changes of endogenous metabolites associated with UC and responses to MF intervention. qRT-PCR analysis was performed to confirm the molecular pathway in vivo. The effects of MF and lysophosphatidylcholine (LPC) on cell viability, wound healing, proliferation, and migration were examined through a series of in vitro experiments. Moreover, the effects of different subtypes of phospholipase A2 (PLA2) inhibitors on MF-treated colonic epithelial cells were detected by wound healing test and transwell assay. RESULTS: Orally administered MF could alleviate colitis in mice mainly by accelerating the healing of colonic mucosa. Guided by an unbiased metabolomics screen, we identified LPC synthesis as a major modifying pathway in colitis mice after MF treatment. Notably, MF facilitated the synthesis of LPC by enhancing the expression of PLA2 in colitis mice. Mechanistically, MF and LPC accelerated wound closure by promoting cell migration. Moreover, the promotion of MF on wound healing and migration of colonic epithelial cells was blunted by a cytosolic phospholipase A2 (cPLA2) inhibitor. CONCLUSION: MF can facilitate colonic mucosal healing of mice with colitis through cPLA2-mediated intestinal LPC synthesis, which may become a novel therapeutic agent of UC.

Optimizing the Extraction and Enrichment of Luteolin from Patrinia villosa and Its Anti-Pseudorabies Virus Activity.

Luteolin from Patrinia villosa exhibits strong antiviral activity. Here, the conditions for extracting and enriching luteolin from P. villosa were optimized. Response surface methodology was used to determine the optimal extraction parameters in terms of reflux time, solvent ratio, extraction temperature, material-to-liquid ratio, and number of extractions. Thereafter, a macroporous resin method was used to enrich luteolin from P. villosa. Finally, the following optimal extraction and enrichment conditions were established: an extraction time of 43.00 min, a methanol/hydrochloric acid solvent ratio of 13:1, an extraction temperature of 77.60 °C, a material/liquid ratio of 1:22, and a total of two extractions. NKA-9 was determined to be the most appropriate resin for enrichment. The ideal adsorption conditions were as follows: a pH of 5.0, a temperature of 25 °C, an initial luteolin concentration of 19.58 µg/mL, a sample loading volume of 2.9 BV, and a sample loading rate of 2 BV/h. The ideal desorption conditions were as follows: distilled water, 30% ethanol and 80% ethanol elution, and 5 BV at a flow rate of 2 BV/h. After optimization, the enrichment recovery rate was 80.06% and the luteolin content increased 3.8-fold. Additionally, the enriched product exhibited a significant inhibitory effect on PRV (Porcine pseudorabies virus) in vitro and in vivo, providing data for developing and applying luteolin from P. villosa.

Model-informed dose optimisation of polymyxin-rifampicin combination therapy against multidrug-resistant Acinetobacter baumannii.

OBJECTIVES: Antimicrobial resistance is a major global threat. Because of the stagnant antibiotic pipeline, synergistic antibiotic combination therapy has been proposed to treat rapidly emerging multidrug-resistant (MDR) pathogens. We investigated antimicrobial synergy of polymyxin/rifampicin combination against MDR Acinetobacter baumannii. METHODS: In vitro static time-kill studies were performed over 48 h at an initial inoculum of ∼107 CFU/mL against three polymyxin-susceptible but MDR A. baumannii isolates. Membrane integrity was examined at 1 and 4 h post-treatment to elucidate the mechanism of synergy. Finally, a semi-mechanistic PK/PD model was developed to simultaneously describe the time course of bacterial killing and prevention of regrowth by mono- and combination therapies. RESULTS: Polymyxin B and rifampicin alone produced initial killing against MDR A. baumannii but were associated with extensive regrowth. Notably, the combination showed synergistic killing across all three A. baumannii isolates with bacterial loads below the limit of quantification for up to 48 h. Membrane integrity assays confirmed the role of polymyxin-driven outer membrane remodelling in the observed synergy. Subsequently, the mechanism of synergy was incorporated into a PK/PD model to describe the enhanced uptake of rifampicin due to polymyxin-induced membrane permeabilisation. Simulations with clinically utilised dosing regimens confirmed the therapeutic potential of this combination, particularly in the prevention of bacterial regrowth. Finally, results from a neutropenic mouse thigh infection model confirmed the in vivo synergistic killing of the combination against A. baumannii AB5075. CONCLUSION: Our results showed that polymyxin B combined with rifampicin is a promising option to treat bloodstream and tissue infection caused by MDR A. baumannii and warrants clinical evaluations.

Effects of natural spring water on the sensory attributes and physicochemical properties of tea infusions.

The sensory quality of tea is influenced by water quality, with natural spring water (NSW) gaining much attention for its natural and healthy qualities. The effects of NSW on the sensory attributes, physicochemical composition, and antioxidant capacity of Chinese tea were investigated. Tea brewed with pure water was the most resistant to oxidation and darkening. NSW with low total dissolved solids (TDS) was most suitable for brewing unfermented or mildly fermented teas, improving their sensory quality. The simulated green tea infusion system was used to investigate further the dramatic darkening of tea infusions in NSW. Exposure of infusions to air promoted the degradation, epimerization, and oxidative polymerization of catechins, and further formed theabrownins which darkened the tea infusions. These findings enabled tea consumers to choose the most suitable NSW for brewing Chinese teas and illustrated the darkening mechanism of tea infusion in high pH/TDS water.

Gestational folic acid supplement prevents vitamin D deficiency-induced depression-like behavior by reversing cortical DNA hypomethylation in adult offspring.

Depression is a common mental disorder with an increasing incidence. Several studies have demonstrated that cortical DNA hypomethylation is associated with depression-like behaviors. This study aims to investigate whether maternal vitamin D deficiency (VDD) induces depression-like behaviors and to explore the effects of folic acid supplement on VDD-induced cortical DNA hypomethylation in adult offspring. Female mice were fed with a VDD diet, beginning at 5 weeks of age and throughout pregnancy. Depression-like behaviors were evaluated, and cortical 5-methylcytosine (5mC) content was detected in adult offspring. Results showed that depression-like behaviors were observed in adult offspring of the VDD group. Cortical Ache and Oxtr mRNAs were upregulated in female offspring of the VDD group. Cortical Cpt1a and Htr1b mRNAs were increased in male offspring of the VDD group. Moreover, cortical 5mC content was reduced in offspring of VDD-fed dams. The additional experiment showed that serum folate and cortical S-adenosylmethionine (SAM) contents were decreased in the offspring of the VDD group. Folic acid supplement attenuated VDD-induced SAM depletion and reversed cortical DNA methylation. Moreover, folic acid supplement attenuated VDD-induced upregulation of depression-related genes. In addition, folic acid supplement alleviated maternal VDD-induced depression-like behaviors in adult offspring. These results suggest that maternal VDD induces depression-like behavior in adult offspring by reducing cortical DNA methylation. The gestational folic acid supplement prevents VDD-induced depression-like behavior by reversing cortical DNA hypomethylation in adult offspring.

A modified Fangji Huangqi decoction ameliorates pulmonary artery hypertension via phosphatidylinositide 3-kinases/protein kinase B-mediated regulation of proliferation and apoptosis of smooth muscle cells in vitro and in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: Pulmonary artery hypertension (PAH) is a progressive and fatal lung disease of multifactorial etiology, which arouses an enhanced interest in PAH disease therapy. Modified Fangji Huangqi decoction (MFJHQ), a traditional Chinese medicine (TCM) formula, has a crucial role in the treatment of PAH. However, the pharmacological roles and mechanisms of MFJHQ on PAH remain unknown. AIM OF THE STUDY: To investigate the effects and potential mechanism of MFJHQ on pulmonary vascular remodeling in PAH. MATERIAL AND METHODS: Ultra-performance liquid chromatography (UPLC) was employed to quantitate the principal components in MFJHQ. Rats were treated with MFJHQ by gavage for final 2 weeks in monocrotaline (MCT)-induced PAH rats. RNA-sequencing and network pharmacology analysis were performed to explore the potential mechanism. The primary rat pulmonary artery smooth muscle cells (PASMCs) were utilized to evaluate the regulatory effect of MFJHQ in vitro. RESULTS: Seven active components from MFJHQ were quantitated by UPLC. In rats with MCT-induced PAH, MFJHQ treatment significantly improved hemodynamic parameters, right ventricular hypertrophy index, lung function, and attenuated pulmonary vascular remodeling. Mechanistically, we further confirmed that MFJHQ inhibits MCT-induced phosphatidylinositide 3-kinases/protein kinase B (PI3K/Akt) pathway predicated by network pharmacology and RNA-sequencing analysis to reduce the proliferation of pulmonary arteries and promote pulmonary artery apoptosis in lung tissues. Additionally, MFJHQ hindered the proliferation and migration, and accelerated apoptosis in PDGF-BB-induced PASMCs in vitro, which can be enhanced by the presence of the PI3K inhibitor LY294002. CONCLUSIONS: Our results indicated that MFJHQ inhibited MCT-induced pulmonary vascular remodeling by decreasing proliferation and migration of PASMCs and promoting PASMC apoptosis through PI3K/Akt pathway, which provides a novel treatment option for PAH with multi-targeting mechanisms inspired by TCM theory.

[Effects of moxibustion on the ultrastructure of synovial cells of knee joint and serum cytokines in adjuvant arthritis rats].

OBJECTIVE: To observe the effects of moxibustion on the ultrastructure of synovial cells of knee joint and serum cytokines in adjuvant arthritis (AA) rats, and to explore the potential mechanism of moxibustion in treatment of rheumatoid arthritis. METHODS: Forty-five Wistar male rats were randomly divided into a normal group, a model group and a moxibustion group, with 15 rats in each group. In the model group and the moxibustion group, the AA model was replicated under wind, cold and humid environment and by injection with complete freund's adjuvant. In the moxibustion group, moxibustion at "Zusanli" (ST 36) and "Shenshu" (BL 23) was used, 20 min each time, once daily, for consecutive 21 days. In the normal group and the model group, no intervention was processed. The scores of the knee joint swelling degree (JSD) and arthritis index (AI) were compared among groups. The ultrastructure of synovial cells of knee joint were observed under transmission electron microscope (TEM). The levels of serum cytokines such as tumor necrosis factor-α (TNF-α), interieukin (IL)-1ß, IL-6 and IL-10 were detected using ELISA method. RESULTS: Compared with the normal group, JSD and AI scores, the levels of TNF-α, IL-1ß and IL-6 were increased (P<0.01), while IL-10 was reduced (P<0.01) in the model group after intervention. JSD and AI scores, and the levels of TNF-α, IL-1ß and IL-6 were lower (P<0.05, P<0.01), while the level of IL-10 was higher (P<0.01) in the moxibustion group compared with the model group. Compared with the normal group, the ultrastructure of synovial cell was obviously damaged in the model group, and the damage was attenuated in the moxibustion group compared with the model group. CONCLUSION: Moxibustion can reduce the symptoms of arthritis in AA rats, which may be related to the improvement of the ultrastructure of synovial cells and the regulation of cytokines.

Phytochemical Analysis and Anti-Ascaris suum Activity of Different Zanthoxylum Species In Vitro and In Vivo.

Zanthoxylum plants (ZPs), including multiple Chinese prickly ash species, are dual-purpose functional foods favored by the general population around the world in foods, cosmetics, and traditional medicines and have antipruritic, insecticidal, and fungicidal bioactivities. For the first time, the anti-roundworm bioactivity of ZPs and the active ingredients were compared and investigated. Through nontarget metabolomics following targeted quantitative analysis, qinbunamides, sanshools, sanshooel, asarinin, and sesamin were found to be the main different components of Zanthoxylum species. Coincidentally, the 12 chemical components were also the dominant anti-roundworm ingredients of ZP extracts. The extracts of three species of Chinese prickly ash (1 mg/mL) decreased the hatchability of roundworm eggs significantly, and the ChuanJiao seed killed roundworms (insecticidal rate 100%) and alleviated the symptoms of pneumonia in mice. Furthermore, retention time-accurate mass-tandem mass spectrometry-ion ratio (RT-AM-MS/MS-IR) were modeled by assaying 108 authentic compounds of ZP extracts, and 20 metabolites were confidently identified in biological samples from ZP extract-treated mice by analyzing the m/z values and the empirical substructures. This study provides a good reference for the proper application of ZPs.