Metals/bisulfite system involved generation of 24-sulfonic-25-ene ginsenoside Rg1, a potential quality control marker for sulfur-fumigated ginseng.

Ginseng is a most popular health-promoting food with ginsenosides as its main bioactive ingredients. Illegal sulfur-fumigation causes ginsenosides convert to toxic sulfur-containing derivatives, and reduced the efficacy/safety of ginseng. 24-sulfo-25-ene ginsenoside Rg1 (25-ene SRg1), one of the sulfur-containing derivatives, is a potential quality control marker of fumigated ginseng, but with low accessibility owing to its unknown generation mechanism. In this study, metals/bisulfite system involved generation mechanism was investigated and verified. The generation of 25-ene SRg1 in sulfur-fumigated ginseng is that SO2, formed during sulfur-fumigation, reacted with water and ionized into HSO3-. On the one hand, under the metals/bisulfite system, HSO3- generates HSO5- and free radicals which converted ginsenoside Rg1 to 24,25-epoxide Rg1; on the other hand, as a nucleophilic group, HSO3- reacted with 24,25-epoxide Rg1 and further dehydrated to 25-ene SRg1. This study provided a technical support for the promotion of 25-ene SRg1 as the characteristic quality control marker of sulfur-fumigated ginseng.

[Effects of maltodextrin on water adsorption and thermodynamic properties of Codonopsis Radix spray-dried powder].

This study aims to reveal the effects of maltodextrin(MD) on the water adsorption and thermodynamic properties of Codonopsis Radix(DS) spray-dried powder by determining the moisture and energy changes of the powder in the process of moisture absorption. The static weighing method was used to obtain the isothermal water adsorption data of the spray-dried powder in 6 saturated salt solutions(KAc, MgCl_2·6H_2O, K_2CO_3, NaBr, NaCl, and KCl) at 3 temperatures(25, 35, and 45 ℃). Six models were used for fitting of the water adsorption process, and the most suitable model was selected based on the model performance. Furthermore, the corresponding net equivalent adsorption heat and differential entropy were calculated, and the adsorption entropy change was integrated. The linear relationship between net equivalent adsorption heat and differential entropy was drawn based on the entropy-enthalpy complementarity theory. The results showed that the water adsorption properties of DS and DS-MD spray-dried powder followed the type Ⅲ isotherm and was well fitted by the GAB model. The monolayer water content M_0 decreased with the increase in temperature. At the same temperature, the M_0 of DS spray-dried powder decreased after the addition of MD. The net equivalent adsorption heat and differential entropy of DS and DS-MD spray-dried powder decreased with the increase in water content, which presented a linear relationship. The addition of MD decreased the water activity corresponding to the lowest integral adsorption entropy of the powder, and the system became more stable. The results indicated that the spray-dried powder became more stable after the addition of MD.

Carpesabrolide A, a novel meroterpenoid with anti-inflammatory activity from Carpesium abrotanoides.

Carpesabrolide A (1), featuring an unprecedented fumaric acid-guaiane sesquiterpenoid hybrid, has been isolated from the folk medicinal plant Carpesium abrotanoides. The structure with absolute configuration has been established by spectroscopic methods and single crystal X-ray diffraction analysis. The plausible biosynthetic pathway for 1 is proposed. Compound 1 shows significant anti-inflammatory activity by inhibiting NO production with an IC50 value of 2.7 µM.

Xijiao Dihuang decoction combined with Yinqiao powder promotes autophagy-dependent ROS decrease to inhibit ROS/NLRP3/pyroptosis regulation axis in influenza virus infection.

BACKGROUND: Influenza viral pneumonia is a common complication after influenza virus infection. Xijiao Dihuang Decoction combined with Yinqiao Powder (XDY) is effective on improving influenza viral pneumonia. PURPOSE: This study further explores the anti-inflammatory mechanism of XDY in the treatment of influenza viral pneumonia. STUDY DESIGN: The effects of XDY on inflammation, autophagy, NACHT-LRR-PYD-containing protein 3 (NLRP3) inflammasome and pyroptosis were assessed in the mice with influenza viral pneumonia. In addition, the mouse macrophage cell line (J774A.1) infected with influenza virus was adopted to decode the in vitro effects of XDY on autophagy, reactive oxygen species (ROS), NLRP3 inflammasome and pyroptosis. We analyzed the XDY-induced autophagy, especially the mitophagy-related ROS clearance, and the subsequent inhibition of ROS/NLRP3 inflammasome/pyroptosis signaling in the infected macrophages by different assays based on quantitative polymerase chain reaction, western blot, flow cytometry, immunofluorescence and enzyme-linked immunosorbent assay. RESULTS: In vivo, XDY could effectively improve the lung inflammatory response in the mice with influenza virus pneumonia, due to an intact autophagy flux-promoting effect and the inhibiting roles on NLRP3 inflammasome and pyroptosis. Notably, in vitro, compared with the infected macrophages treated by the NLRP3 inflammasome agonist (Monosodium urate) or the mitochondrial-targeted antioxidant agent, the XDY-dependent treating could inhibit pyroptosis by negatively regulating the signaling axis of ROS/NLRP3 inflammasome/pyroptosis in the influenza virus-infected macrophages. More interestingly, XDY could promote an intact autophagy flux, inducing mitophagy eliminating the damaged mitochondria to reduce the intracellular ROS accumulation, and thus decrease the oxidative stress in the infected macrophages. Especially, the inhibitor of autophagy inition, 3-Methyladenine, could reverse the inhibitory effect of XDY on ROS-NLRP3 inflammasome-mediated pyroptosis, indicating an XDY-promoted mitophagy-dependent ROS scavenging. CONCLUSION: XDY can promote an intact autophagy flux to eliminate damaged mitochondria, namely mitophagy, which reduces the intracellular ROS accumulation contributing to NLRP3 inflammasome activation, restricting pyroptosis and eventually alleviating the influenza virus-induced inflammatory lesions. The obtained results provide new insights into the mechanism of action of XDY in alleviating influenza virus pneumonia, especially the roles of XDY in anti-oxidation, anti-inflammation and anti-pyroptosis, with potential therapeutic targets for future application in integrative medicine.

Tangshen Formula alleviates inflammatory injury against aged diabetic kidney disease through modulating gut microbiota composition and related amino acid metabolism.

Diabetic kidney disease (DKD) is leading causes and one of the fastest growing causes of chronic kidney disease worldwide, and leads to high morbidity and mortality. Emerging evidences have revealed gut microbiota dysbiosis and related metabolism dysfunction play a dominant role in DKD progression and treatment through modulating inflammation. Our previous studies showed that Tangshen Formula (TSF), a Chinese herbal prescription, exhibited anti-inflammatory effect on DKD, but underlying mechanism that involved gut microbiota and related metabolism in aged model remained obscure. Here, BTBR ob/ob mice were used to establish aged DKD model, and 16S rRNA sequence and untargeted metabolomic analyses were employed to investigate the correlation between colonic microbiota and serum metabolism. The aged ob/ob mice exhibited obvious glomerular and renal tubule injury and kidney function decline in kidney, while TSF treatment significantly attenuated these abnormalities. TSF also exhibited potent anti-inflammatory effect in aged ob/ob mice indicating by reduced proinflammatory factor IL-6 and TNF-α, MCP-1 and COX-2 in serum, kidney and intestine, which suggested the involvement of gut microbiota with TSF effect. The 16S rDNA sequencing of the colonic microbiome and untargeted serum metabolomics analysis revealed significant differences in gut microbiota structure and serum metabolomic profiles between WT and ob/ob mice. Notably, TSF treatment reshaped the structure of gut microbiota and corrected the disorder of metabolism especially tryptophan metabolism and arginine biosynthesis. TSF increased Anaeroplasma and Barnesiella genera and decreased Romboutsia, Akkermansia, and Collinsella genera, and further elevated tryptophan, 5-hydroxyindoleacetate, glutamic acid, aspartate and reduced 4-hydroxy-2-quinolinecarboxylic acid, indole-3-acetic acid, xanthurenic acid, glutamine. Further correlation analysis indicated that disturbed gut microbiota was linked to tryptophan metabolism and arginine biosynthesis to regulate inflammation in aged DKD. Our data revealed that TSF attenuated renal inflammation by modulating gut microbiota and related amino acid metabolism in aged DKD model, highlighting gut microbiota and related metabolism functioned as potential therapeutic target for DKD in elderly patients.

Platycodin D facilitates antiviral immunity through inhibiting cytokine storm via targeting K63-linked TRAF6 ubiquitination.

Influenza virus infection is a worldwide challenge that causes heavy burdens on public health. The mortality rate of severe influenza patients is often associated with hyperactive immunological abnormalities characterized by hypercytokinemia. Due to the continuous mutations and the occurrence of drug-resistant influenza virus strains, the development of host-directed immunoregulatory drugs is urgently required. Platycodon grandiflorum is among the top 10 herbs of traditional Chinese medicine used to treat pulmonary diseases. As one of the major terpenoid saponins extracted from Platycodon grandiflorum, Platycodin D (PD) has been reported to play several roles, including anti-inflammation, analgesia, anti-cancer, hepatoprotection, and immunoregulation. However, the therapeutic roles of PD to treat influenza virus infection remains unknown. Here, we show that PD can protect the body weight loss in severely infected influenza mice, alleviate lung damage, and thus improve the survival rate. More specifically, PD protects flu mice via decreasing the immune cell infiltration into lungs and downregulating the overactivated inflammatory response. Western blot and immunofluorescence assays exhibited that PD could inhibit the activation of TAK1/IKK/NF-κB and MAPK pathways. Besides that, CETSA, SPR and immunoprecipitation assays indicated that PD binds with TRAF6 to decrease its K63 ubiquitination after R837 stimulation. Additionally, siRNA interference experiments exhibited that PD could inhibit the secretion of IL-1ß and TNF-α in TRAF6-dependent manner. Altogether, our results suggested that PD is a promising drug candidate for treating influenza. Our study also offered a scientific explanation for the commonly used Platycodon grandiflorum in many anti-epidemic classic formulas. Due to its host-directed regulatory role, PD may serve as an adjuvant therapeutic drug in conjunction with other antiviral drugs to treat the flu.

A Poisoning Case Involving Gymnopus dryophiloides (Agaricomycetes).

Recently, mushroom poisoning is becoming one of the most serious food safety problems in China, especially in Yunnan province. However, there is insufficient information on many poisoning incidents, including mushroom information, identification and poisoning symptoms etc. In October 2022, a female midwife in Yunnan province consumed a wild mushroom twice. Detailed epidemiological investigation and mushroom identification were performed in this report. Based on morphological and phylogenetic analysis, the suspected mushroom was identified as Gymnopus dryophiloides (Omphalotaceae, Agaricomycetes). The victim reported nausea, vomiting, diarrhea, stomachache, accompanied by dizziness, headache, drowsiness, chest tightness, shortness of breath, palpitation, and weakness. The incubation period was approximately 30 min. After the victim's own vomiting, the symptoms began to subside for about an hour. Up to date, there are no detailed reports of poisoning in G. dryophiloides. In conclusion, it is the first detailed poisoning report of G. dryophiloides in the world.

Acupoint selection rules of acupuncture for Tourette syndrome in children. / 针刺治疗儿童Tourette综合征选穴规律.

OBJECTIVES: To explore the rules of acupoint selection and compatibility of acupuncture for Tourette syndrome(TS) in children. METHODS: The relevant literature regarding acupuncture for Tourette syndrome in children included in CNKI, Wanfang, VIP, SinoMed, PubMed, Web of Science and Cochrane Library from the establishment of the database to March 31st, 2023 was retrieved.The information of acupuncture prescription, syndrome type, meridian affinity was extracted to set up database. The Microsoft Excel 2019 was used for descriptive statistical analysis, SPSS modeler18.0 was for association rule analysis, lantern5.0 was for latent structure analysis and comprehensive clustering. RESULTS: ①A total of 80 literature was included, and 112 acupuncture prescriptions were extracted, involving 104 acupoints, with a cumulative frequency of 859 times.②The acupoints with high use frequency were Taichong(LR 3), Baihui(GV 20), Fengchi(GB 20), Hegu(LI 4), Sishencong(EX-HN 1), Sanyinjiao(SP 6) and Zusanli(ST 36).③In the treatment of TS with acupuncture, the governor vessel acupoints were the most frequently used, the proportion of acupoints on the head, face, neck and lower limbs was higher. ④The association rule analysis showed that Fengchi(GB 20)-Hegu(LI 4) and Taichong(LR 3)-Hegu(LI 4) had the highest support degree, both were 47.32%.⑤Five comprehensive clustering models were obtained by analyzing the latent structure of high-frequency acupoints, corresponding to yin deficiency disturbing wind, liver hyperactivity and spleen deficiency, liver yang transforming into wind, phlegm-heat harassing the interior and qi stagnation transformed fire. CONCLUSIONS: Acupuncture for TS in children is based on the principle of soothe the liver and extinguish the wind, regulating qi and blood, and paying attention to regulating spirit and qi. The core acupoints are Fengchi(GB 20), Hegu(LI 4), Taichong(LR 3), Baihui(GV 20), Sanyinjiao(SP 6) , Zusanli(ST 36), acupoints should be selected according to different syndrome in clinical.

Effects of hyperbaric oxygen combined cabin ventilator on critically ill patients with liberation difficulty after tracheostomy.

BACKGROUND: Critically ill patients undergoing liberation often encounter various physiological and clinical complexities and challenges. However, whether the combination of hyperbaric oxygen and in-cabin ventilator therapy could offer a comprehensive approach that may simultaneously address respiratory and potentially improve outcomes in this challenging patient population remain unclear. METHODS: This retrospective study involved 148 patients experiencing difficulty in liberation after tracheotomy. Inclusion criteria comprised ongoing mechanical ventilation need, lung inflammation on computed tomography (CT) scans, and Glasgow Coma Scale (GCS) scores of ≤ 9. Exclusion criteria excluded patients with active bleeding, untreated pneumothorax, cerebrospinal fluid leakage, and a heart rate below 50 beats per minute. Following exclusions, 111 cases were treated with hyperbaric oxygen combined cabin ventilator, of which 72 cases were successfully liberated (SL group) and 28 cases (NSL group) were not successfully liberated. The hyperbaric oxygen chamber group received pressurization to 0.20 MPa (2.0 ATA) for 20 min, followed by 60 min of ventilator oxygen inhalation. Successful liberation was determined by a strict process, including subjective and objective criteria, with a prolonged spontaneous breathing trial. GCS assessments were conducted to evaluate consciousness levels, with scores categorized as normal, mildly impaired, moderately impaired, or severely impaired. RESULTS: Patients who underwent treatment exhibited improved GCS, blood gas indicators, and cardiac function indexes. The improvement of GCS, partial pressure of oxygen (PaO2), oxygen saturation of blood (SaO2), oxygenation index (OI) in the SL group was significantly higher than that of the NSL group. However, there was no significant difference in the improvement of left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV), left ventricular end-diastolic volume (LVEDV), and stroke volume (SV) between the SL group and the NSL group after treatment. CONCLUSIONS: Hyperbaric oxygen combined with in-cabin ventilator therapy effectively enhances respiratory function, cardiopulmonary function, and various indicators of critically ill patients with liberation difficulty after tracheostomy.

Schisandrin A alleviates renal fibrosis by inhibiting PKCß and oxidative stress.

BACKGROUND: Renal fibrosis is a common pathway that drives the advancement of numerous kidney maladies towards end-stage kidney disease (ESKD). Suppressing renal fibrosis holds paramount clinical importance in forestalling or retarding the transition of chronic kidney diseases (CKD) to renal failure. Schisandrin A (Sch A) possesses renoprotective effect in acute kidney injury (AKI), but its effects on renal fibrosis and underlying mechanism(s) have not been studied. STUDY DESIGN: Serum biochemical analysis, histological staining, and expression levels of related proteins were used to assess the effect of PKCß knockdown on renal fibrosis progression. Untargeted metabolomics was used to assess the effect of PKCß knockdown on serum metabolites. Unilateral Ureteral Obstruction (UUO) model and TGF-ß induced HK-2 cells and NIH-3T3 cells were used to evaluate the effect of Schisandrin A (Sch A) on renal fibrosis. PKCß overexpressed NIH-3T3 cells were used to verify the possible mechanism of Sch A. RESULTS: PKCß was upregulated in the UUO model. Knockdown of PKCß mitigated the progression of renal fibrosis by ameliorating perturbations in serum metabolites and curbing oxidative stress. Sch A alleviated renal fibrosis by downregulating the expression of PKCß in kidney. Treatment with Sch A significantly attenuated the upregulated proteins levels of FN, COL-I, PKCß, Vimentin and α-SMA in UUO mice. Moreover, Sch A exhibited a beneficial impact on markers associated with oxidative stress, including MDA, SOD, and GSH-Px. Overexpression of PKCß was found to counteract the renoprotective efficacy of Sch A in vitro. CONCLUSION: Sch A alleviates renal fibrosis by inhibiting PKCß and attenuating oxidative stress.

Integrating Transcriptome and Chemical Analyses to Provide Insights into Biosynthesis of Terpenoids and Flavonoids in the Medicinal Industrial Crop Andrographis paniculate and Its Antiviral Medicinal Parts.

Andrographis paniculata is a medicinal plant traditionally used to produce diterpene lactones and flavonoids, which possess various biological activities. Widely distributed in China, India, and other Southeast Asia countries, A. paniculata has become an important economic crop, significantly treating SARS-CoV-2, and is being cultivated on a large scale in southern China. The biosynthesis of active ingredients in A. paniculata are regulated and controlled by genes, but their specific roles are still not fully understood. To further explore the growth regulation factors and utilization of its medicinal parts of this industrial crop, chemical and transcriptome analyses were conducted on the roots, stems, and leaves of A. paniculata to identify the biosynthesis pathways and related candidate genes of the active ingredients. The chemical analysis revealed that the main components of A. paniculata were diterpene lactones and flavonoids, which displayed potential ability to treat SARS-CoV-2 through molecular docking. Moreover, the transcriptome sequencing annotated a total of 40,850 unigenes, including 7962 differentially expressed genes. Among these, 120 genes were involved in diterpene lactone biosynthesis and 60 genes were involved in flavonoid biosynthesis. The expression of diterpene lactone-related genes was the highest in leaves and the lowest in roots, consistent with our content determination results. It is speculated that these highly expressed genes in leaves may be involved in the biosynthesis pathway of diterpenes. Furthermore, two class Ⅰ terpene synthases in A. paniculata transcriptome were also annotated, providing reference for the downstream pathway of the diterpene lactone biosynthesis. With their excellent market value, our experiments will promote the study of the biosynthetic genes for active ingredients in A. paniculata and provide insights for subsequent in vitro biosynthesis.

Effect of mindfulness-based interventions on people with prehypertension or hypertension: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Hypertension and prehypertension have been widely recognized as the main contributors of global mortality. Evidence shows mindfulness-based interventions may reduce blood pressure and improve mental health. However, the effect of mindfulness-based interventions on blood pressure and mental health has not been fully understood. METHODS: Potential studies published before May 24th 2023 were identified by searching Embase, Ovid Emcare, PsycINFO, CINAHL, Web of Science, Cochrane, PubMed, China National Knowledge Infrastructure, Wanfang database, and VIP China Science. Additionally, two grey databases were searched: Mednar, WorldWideScience.org. The risk of bias in the included studies was assessed using the Cochrane Risk of Bias Assessment tool. The random-effects meta-analyses were conducted using Review Man 5.4 software and the key outcomes are presented as mean difference or standard mean difference and the 95% confidential interval. RESULTS: Searches returned 802 studies in total, of which 12 were included (N = 715). The duration of interventions was 8 weeks in 10 trials and 6 weeks in one trial. Pooled effect sizes indicated reductions in systolic blood pressure (MD = - 9.12, 95% CI [- 12.18, - 6.05], p < 0.001), diastolic blood pressure (MD = - 5.66, 95% CI [- 8.88, - 2.43], p < 0.001), anxiety (SMD = - 4.10; 95% CI [- 6.49, - 1.71], p < 0.001), depression (SMD = - 1.70, 95%CI [- 2.95, - 0.44], p < 0.001) and perceived stress (SMD = - 5.91, 95%CI [- 8.74, - 3.09], p < 0.001) at post-intervention. The findings from subgroup analyses are favorable for mindfulness-based interventions regardless of gender and baseline blood pressure with regard to BP reduction, with a more profound effect observed in participants with higher pre-intervention blood pressure. CONCLUSIONS: The results provide evidence for the positive role of mindfulness-based interventions in hypertension management. More large randomized control trials with sufficient statistical power and long-term follow-up are needed. TRIAL REGISTRATION: The protocol had been registered with Prospero on October 2nd 2021 (registration NO. CRD42021282504 ).

Clinical efficacy of traditional Chinese medicine therapy for female stress urinary incontinence: a meta-analysis.

OBJECTIVES: To investigate the efficacy of traditional Chinese medicine (TCM) in the treatment of female stress urinary incontinence (SUI). METHOD: PubMed, Cochrane, Web of Science, Embase, CNKI, Wanfang, and VIP databases were searched for articles published up to September 2022. Variables were analyzed using weighted mean difference (WMD), standardized mean difference (SMD), odds ratios (OR), and 95% confidence interval (CI). RESULTS: Eight studies containing 744 patients were included in this study. The results demonstrate that TCM therapy had more advantages in improving the clinical outcome of SUI patients (OR = 2.90, 95%CI:1.92-4.37, P = 0.000), reducing the International Consultation on Incontinence Questionnaire Short-Form (ICIQ-SF) score (WMD = -2.41, 95%CI:-2.83- -1.98, P = 0.000), reducing 1-h urinary pad leakage urine volume (WMD = -1.86, 95%CI:-2.23- -1.49, P = 0.000) and increasing Maximum urethral closure pressure (MUCP) (SMD = 0.86, 95%CI: 0.61-1.11, P = 0.000). CONCLUSION: TCM therapy is effective in improving urinary incontinence symptoms, urodynamics, and quality of life in patients with SUI. This article provides a reference for the application of TCM therapy in women with urinary incontinence.

Acupuncture and moxibustion for irritable bowel syndrome: An umbrella systematic review.

BACKGROUND: Irritable bowel syndrome (IBS) is a functional bowel disease characterized by abdominal pain or discomfort associated with altered bowel habits. Several clinical studies have demonstrated the effectiveness of acupuncture and moxibustion for IBS. Many systematic reviews of acupuncture and moxibustion for IBS have been published in recent years, but their results are not entirely consistent. OBJECTIVE: To evaluate the methodological, reporting, and evidence quality of systematic reviews of acupuncture and moxibustion for IBS. SEARCH STRATEGY: Systematic reviews of acupuncture and moxibustion for IBS published before February 20, 2023 were searched in eight databases: PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang Data, VIP Database for Chinese Technical Periodicals, and China Biology Medicine. The keywords used for literature search were acupuncture, moxibustion, systematic review, meta-analysis, and irritable bowel syndrome. INCLUSION CRITERIA: Systematic reviews and meta-analyses of randomized controlled trials of acupuncture and moxibustion for IBS were included. DATA EXTRACTION AND ANALYSIS: Relevant information was independently extracted by two investigators. The A MeaSurement Tool to Assess systematic Reviews 2 (AMSTAR 2), Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020), and Grading of Recommendations Assessment, Development and Evaluation (GRADE) were used to evaluate the methodological quality, reporting quality and evidence quality, respectively. RESULTS: A total of 342 studies were retrieved and 15 systematic reviews were included. The results of AMSTAR 2 showed low methodological quality in 2 studies and very low methodological quality in the remaining 13 studies, with main issues being failure to register a protocol, incomplete search strategy, not providing a list of excluded studies, incomplete consideration of the risk of bias in the included studies, and a failure to assess the publication bias. The results of PRISMA 2020 showed seriously deficient reporting quality of 2 studies, somewhat deficient reporting quality of 12 studies, and relatively complete reporting quality of 1 study, with the main problems being lack of a complete search strategy, non-availability of a list of excluded studies with justification for their exclusion, not conducting heterogeneity and sensitivity analyses, not evaluating the credibility of the evidence, and not registering the protocol. The results of GRADE showed that the quality of the evidence is low or very low. CONCLUSION: Most included systematic reviews interpreted findings to suggest that acupuncture and moxibustion have benefits for IBS. However, there is a need to improve the methodological, reporting and evidence quality of the systematic reviews. Larger, multicenter, rigorously designed randomized controlled trials and high-quality systematic reviews are required to obtain more robust evidence. PLEASE CITE THIS ARTICLE AS: Ma YY, Hao Z, Chen ZY, Shen YX, Liu HR, Wu HG, Bao CH. Acupuncture and moxibustion for irritable bowel syndrome: An umbrella systematic review. J Integr Med. 2024; 22(1): 22-31.

Pien Tze Huang Inhibits Proliferation of Colorectal Cancer Cells through Suppressing PNO1 Expression and Activating p53/p21 Signaling Pathway.

OBJECTIVE: To explore the regulatory effect of Pien Tze Huang (PZH) on targeting partner of NOB1 (PNO1) and it's down-stream mediators in colorectal cancer (CRC) cells. METHODS: Quantitative polymerase chain reaction was performed to determine mRNA levels of PNO1, TP53, and CDKN1A. Western blotting was performed to determine protein levels of PNO1, p53, and p21. HCT-8 cells were transduced with a lentivirus over-expressing PNO1. Colony formation assay was used to detect cell survival in PNO1 overexpression of HCT-8 cells after PZH treatment. Cell-cycle distribution, cell viability and cell apoptosis were performed to identify the effect of PNO1 overexpression on cell proliferation and apoptosis of HCT-8 cells after PZH treatment. Xenograft BALB/c nude mice bearing HCT116 cells transduced with sh-PNO1 or sh-Ctrl lentivirus were evaluated. Western blot assay was performed to detect PNO1, p53, p21 and PCNA expression in tumor sections. Terminal deoxynucleotidyl transferase dUTP nick end labling (TUNEL) assay was used to determine the apoptotic cells in tissues. RESULTS: PZH treatment decreased cell viability, down-regulated PNO1 expression, and up-regulated p53 and p21 expressions in HCT-8 cells (P<0.05). PNO1 overexpression attenuated the effects of PZH treatment, including the expression of p53 and p21, cell growth, cell viability, cell cycle arrest and cell apoptosis in vitro (P<0.05). PNO1 knockdown eliminated the effects of PZH treatment on tumor growth, inhibiting cell proliferation inhibition and apoptosis induction in vivo (P<0.05). Similarly, PNO1 knockdown attenuated the effects of PZH treatment on the down-regulation of PNO1 and up-regulation of p53 and p21 in vivo (P<0.05). CONCLUSION: The mechanism by which PZH induces its CRC anti-proliferative effect is at least in part by regulating the expression of PNO1 and its downstream targets p53 and p21.

Effects of naturally aged microplastics on the distribution and bioavailability of arsenic in soil aggregates and its accumulation in lettuce.

Naturally aged microplastics (NAMPs) and arsenic (As) have been reported to coexist in and threaten potentially to soil-plant ecosystem. The research explored the combined toxic effects of NAMPs and As to lettuce (Lactuca sativa L.) growth, and the distribution, accumulation and bioavailability of As in soil aggregates. The As contaminated soil with low, medium and high concentrations (L-As, M-As, H-As) were treated with or without NAMPs, and a total of six treatments. The results displayed that, in comparison to separate treatments of L-As and M-As, the presence of NAMPs increased the total biomass of lettuce grown at these two As concentrations by 68.9 % and 55.4 %, respectively. Simultaneous exposure of NAMPs and L-As or M-As led to a decrease in As content in shoot (0.45-2.17 mg kg-1) and root (5.68-14.66 mg kg-1) of lettuce, indicating an antagonistic effect between them. In contrast, co-exposure to H-As and NAMPs showed synergistic toxicity, and the leaf chlorophyll and nutritional quality of lettuce were also reduced. NAMPs altered the ratio of different soil aggregate fractions and the distribution of bioavailable As within them, which influenced the absorption of As by lettuce. In conclusion, these direct observations assist us in enhancing the comprehend of the As migration and enrichment characteristics in soil-plant system under the influence of NAMPs.

Polydopamine Nanostructure-Enhanced Water Interaction with pH-Responsive Manganese Sulfide Nanoclusters for Tumor Magnetic Resonance Contrast Enhancement and Synergistic Ferroptosis-Photothermal Therapy.

Rational structure design benefits the development of efficient nanoplatforms for tumor theranostic application. In this work, a multifunctional polydopamine (PDA)-coated manganese sulfide (MnS) nanocluster was prepared. The polyhydroxy structure of PDA enhanced the water interaction with pH-responsive MnS nanoclusters via hydrogen bonds. At pH 5.5 conditions, the spin-lattice relaxation rate of MnS nanoclusters dramatically increased from 5.76 to 19.33 mM-1·s-1 after the PDA coating, which can be beneficial for efficient tumor magnetic resonance imaging. In addition, PDA endowed MnS nanoclusters with excellent biocompatibility and good photothermal conversion efficiency, which can be used for efficient tumor photothermal therapy (PTT). Furthermore, MnS nanoclusters possess the ability to release H2S in the acidic tumor microenvironment, effectively inhibiting mitochondrial respiration and adenosine triphosphate production. As a result, the expression of heat shock protein was obviously reduced, which can reduce the resistance of tumor cells to photothermal stimulation and enhance the efficacy of PTT. The released Mn2+ also displayed efficient peroxidase and glutathione oxidase-like activity, effectively inducing tumor cell ferroptosis and apoptosis at the same time. Therefore, this nanoplatform could be a potential nanotheranostic for magnetic resonance contrast enhancement and synergistic ferroptosis-PTT of tumors.

Exploring quality evaluation markers of Fructus Psoraleae based on chemometric analysis integrated with network pharmacology.

INTRODUCTION: Fructus Psoraleae (FP) is a well-known traditional Chinese medicine for the treatment of osteoporosis. However, major quality differences were witnessed owing to its various origins, thus influencing its safety and efficacy. OBJECTIVES: The study aimed to evaluate the quality of FP from different origins and predict its quality evaluation markers. METHODS: Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry was employed for tentative characterisation of the constituents in 10 batches of FP, followed by the utilisation of multivariate statistical analysis methods including principal component analysis and orthogonal partial least squares discriminant analysis for quality evaluation. Network pharmacology approaches were utilised to explore the underlying mechanism of the screened chemotaxonomic markers in treating osteoporosis. RESULTS: Forty-one components in FP including, chalcones, coumarins, coumestans, flavonoids, iso-flavonoids, and phenolics, were characterised based on their fragmentation pathways. Ten batches of FP were basically divided into three categories, and eight chemotaxonomic markers including isopsoralen, calamenene, bakuchiol, psoralen, bavachinin, isoneobavaisoflavone, corylifol C, and neobavaisoflavone were screened. Network pharmacology revealed that the chemotaxonomic markers can act on targets such as AKT1, HSP90AA1, and EGFR and possess effects mainly through glycolysis and wnt/ß-catenin signalling to alleviate osteoporosis. Molecular docking and molecular dynamic simulation confirmed the good binding affinity and stability between proteins and selected markers. So, eight chemotaxonomic markers were all preferentially recommended as quality evaluation markers. CONCLUSION: The study not only provides a reference for the improvement of quality control of FP but also offers a theoretical basis for its further in-depth research in osteoporosis.

Aloe-emodin from Sanhua Decoction inhibits neuroinflammation by regulating microglia polarization after subarachnoid hemorrhage.

ETHNOPHARMACOLOGICAL RELEVANCE: Subarachnoid hemorrhage (SAH) triggers a cascade of events that lead to early brain injury (EBI), which contributes to poor outcomes and appears within 3 days after SAH initiation. EBI involves multiple process including neuronal death, blood-brain barrier (BBB) injury and inflammation response. Microglia are cluster of immune cells originating in the brain which respond to SAH by changing their states and releasing inflammatory molecules through various signaling pathways. M0, M1, M2 are three states of microglia represent resting state, promoting inflammation state, and anti-inflammation state respectively, which can be modulated by pharmacological strategies. AIM OF THE STUDY: After identified potential active ingredients and targets of Sanhua Decoction (SHD) for SAH, we selected aloe-emodin (AE) as a potential ingredient modulating microglia activation states. MATERIALS AND METHODS: Molecular mechanisms, targets and pathways of SHD were reveal by network pharmacology technique. The effects of AE on SAH were evaluated in vivo by assessing neurological deficits, neuronal apoptosis and BBB integrity in a mouse SAH model. Furthermore, BV-2 cells were used to examine the effects of AE on microglial polarization. The influence of AE on microglia transformation was measured by Iba-1, TNF-α, CD68, Arg-1 and CD206 staining. The signal pathways of neuronal apoptosis and microglia polarization was measured by Western blot. RESULTS: Network pharmacology identified potential active ingredients and targets of SHD for SAH. And AE is one of the active ingredients. We also confirmed that AE via NF-κB and PKA/CREB pathway inhibited the microglia activation and promoted transformation from M1 phenotype to M2 at EBI stage after SAH. CONCLUSIONS: AE, as one ingredient of SHD, can alleviate the inflammatory response and protecting neurons from SAH-induced injury. AE has potential value for treating SAH-induced nerve injury and is expected to be applied in clinical practice.

Zuogui pill disrupt the malignant cycle in breast cancer bone metastasis through the Piezo1-Notch-1-GPX4 pathway and active molecules fishing.

BACKGROUND: Breast cancer bone metastasis is closely associated with the bone microenvironment. Zuogui Pill (ZGP), a clinically approved formulation in China, effectively regulates the bone microenvironment for the prevention and treatment of osteoporosis. PURPOSE: Few reports have utilized the ZGP for bone metastasis models. This study investigated the intervention and bone-protective properties of ZGP against breast cancer bone metastasis, explored the potential mechanism, and screened for its active compositions by molecules fishing. METHODS: To investigate the intervention efficacy of ZGP and its protein-level mechanism of action, the mouse bone metastasis model and in vitro cell co-culture model were constructed. Affinity ultrafiltration, molecular docking, cellular thermal shift assay and physical scale detection were used to investigate the affinity components of the RANKL protein in ZGP. RESULTS: The administration of ZGP combined with zoledronic acid inhibited the development of tumors and secondary lung metastasis in mice. This translated to a prolonged survival period and enhanced quality of life. ZGP could disrupt the malignant cycle by modulating the Piezo1-Notch-1-GPX4 signaling pathway in the "bone-cancer" communication in the cell co-culture model. Furthermore, 25 chemical components of ZGP were identified, with 10 active compounds exhibiting significant affinity for the RANKL protein. CONCLUSION: The findings of this work highlighted ZGP's potential for intervening in the progression of breast cancer bone metastasis. Thus, this investigation served as an experimental foundation for expanding the application scope of ZGP and for advancing drug development efforts in bone metastasis treatment.