Phosphocholine-induced energy source shift alleviates mitochondrial dysfunction in lung cells caused by geospecific PM2.5 components.

Fine particulate matter (PM2.5) is globally recognized for its adverse implications on human health. Yet, remain limited the individual contribution of particular PM2.5 components to its toxicity, especially considering regional disparities. Moreover, prevention solutions for PM2.5-associated health effects are scarce. In the present study, we comprehensively characterized and compared the primary PM2.5 constituents and their altered metabolites from two locations: Taiyuan and Guangzhou. Analysis of year-long PM2.5 samples revealed 84 major components, encompassing organic carbon, elemental carbon, ions, metals, and organic chemicals. PM2.5 from Taiyuan exhibited higher contamination, associated health risks, dithiothreitol activity, and cytotoxicities than Guangzhou's counterpart. Applying metabolomics, BEAS-2B lung cells exposed to PM2.5 from both cities were screened for significant alterations. A correlation analysis revealed the metabolites altered by PM2.5 and the critical toxic PM2.5 components in both regions. Among the PM2.5-down-regulated metabolites, phosphocholine emerged as a promising intervention for PM2.5 cytotoxicities. Its supplementation effectively attenuated PM2.5-induced energy metabolism disorder and cell death via activating fatty acid oxidation and inhibiting Phospho1 expression. The highlighted toxic chemicals displayed combined toxicities, potentially counteracted by phosphocholine. Our study offered a promising functional metabolite to alleviate PM2.5-induced cellular disorder and provided insights into the geo-based variability in toxic PM2.5 components.

Systematic characterization of the chemical constituents in vitro and in vivo of Qianghuo by UPLC-Q-TOF-MS/MS.

The Chinese herb Qianghuo is an antiphlogistic herb with many effects and complex components. In this study, the chemical composition of Qianghuo and its components in rat plasma after oral administration were investigated using ultra-high-performance liquid chromatography coupled with quadrupole-time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS). The extracts, blank plasma, and plasma containing the drug were analyzed by mass spectrometry, and data collected in both positive and negative ion modes were analyzed using Masslynx software, and the structures were confirmed by combining the compound fragment ions and mass spectrometry cleavage pathways. A total of 62 in vitro chemical components were identified, including 27 coumarins, 18 organic acids, 5 amino acids, 5 glycosides, 2 flavonoids, 4 nucleotides, and 1 ester, which were summarized from the obtained compounds in terms of their possible cleavage patterns. Among the identified 31 compounds in rat plasma, 21 were prototypes, mostly coumarins, organic acids, and flavonoids, and 10 were metabolites, which were mainly generated via hydroxylation and methylation pathways. Based on these, this study provides a theoretical foundation for quality control and basic research on Qianghuo medicinal substances.

Stem cell landscape aids in tumor microenvironment identification and selection of therapeutic agents in gastric cancer.

Gastric cancer stem cells (GCSCs) are strongly associated with the refractory characteristics of gastric cancer, including drug resistance, recurrence, and metastasis. The prognosis for advanced gastric cancer patients treated with multimodal therapy after surgery remains discouraging. GCSCs hold promise as therapeutic targets for GC patients. We obtained 26 sets of stem cell-related genes from the StemChecker database. The Consensus clustering algorithm was employed to discern three distinct stemness subtypes. Prognostic outcomes, components of the tumor microenvironment (TME), and responses to therapies were compared among these subtypes. Following this, a stemness-risk model was formulated using weighted gene correlation network analysis (WGCNA), alongside Cox regression and random survival forest analyses. The C2 subtype predominantly showed enrichment in negative prognostic CSC gene sets and demonstrated an immunosuppressive TME. This specific subtype exhibited minimal responsiveness to immunotherapies and demonstrated reduced sensitivity to drugs. Four pivotal genes were integrated into the construction of the stemness model. Gastric cancer patients with higher stemness-risk scores demonstrated poorer prognoses, a greater presence of immunosuppressive components in TME, and lower rates of treatment response. Subset analysis indicated that only the low-stemness risk subtype derives benefit from 5-fluorouracil-based adjuvant chemotherapy. The model's effectiveness in immunotherapeutic prediction was further validated in the PRJEB25780 cohort. Our study categorized gastric cancer patients into three stemness subtypes, each demonstrating distinct prognoses, components of TME infiltration, and varying sensitivity or resistance to standard chemotherapy or targeted therapy. We propose that the stemness risk model may help the development of well-grounded treatment recommendations and prognostic assessments.

Assessing the Understanding of Helicobacter pylori Infection Among Chinese Pediatricians.

Background: Helicobacter pylori (Hp) is a global public health concern, particularly among children. While the "detection and treatment" approach gains ground in adult patients, paediatricians have divergent opinions regarding the current clinical protocols for diagnosing and treating Hp infection. Some argue for its potential impact on children's growth, emphasizing the need for adequate attention. Additionally, there are uncertainties regarding the appropriate screening tests for children who require Hp testing or have functional dyspepsia. Objective: This study aims to investigate pediatricians' current perspectives and understanding of Hp infection to provide valuable insights for Hp treatment. Methods: This study employs a cross-sectional research design. A questionnaire was designed using the "Questionnaire Star" platform and distributed online to physicians participating in the 12th Shanghai Pediatric Gastroenterology Forum in September 2020. The questionnaire covered topics such as physician professional information, the status of Hp diagnosis in hospitals, Hp knowledge, and knowledge of Hp treatment. Categorical data from each group were analyzed using chi-square tests to understand the diagnostic and treatment practices of pediatricians regarding Hp infection. Results: Among the 218 participating physicians who completed the questionnaire, 49.5% specialized in gastroenterology and practiced in hospitals equipped with Hp testing capabilities. Additionally, 85.8% practiced in hospitals with electronic gastroscopes. Notably, 94% considered Hp an infectious disease. Pediatric gastroenterology specialists, in particular, favored endoscopy for Hp detection compared to non-pediatric gastroenterologists. The investigation revealed variations in Hp detection understanding and consensus among the enrolled physicians. Challenges included determining the age for initiating Hp treatment in children and implementing family-based strategies. Conclusions: Further research is essential to inform the development of comprehensive detection and treatment strategies for Hp infection in children. Currently, the primary approach may involve individualized and standardized diagnosis and treatment.

[Research progress on oxaliplatin-induced neurotoxicity in traditional Chinese medicine (TCM) and western medical cognition and prevention and treatment by TCM].

Chemotherapy is one of the main options in clinical tumor treatment. Although chemotherapy drugs have a good therapeutic effect, they can also cause a series of adverse reactions, such as neurotoxicity. Chemotherapy-induced neurotoxicity is a dose-limi-ting adverse reaction that significantly affects patients' long-term treatment and quality of life. This article reviewed literature from 2000 to the present on chemotherapy-induced neurotoxicity and found that oxaliplatin was the most frequently used chemotherapy drug. Based on the clinical characteristics of oxaliplatin-induced neurotoxicity, this article summarized the understanding of its pathogenesis from both traditional Chinese medicine(TCM) and western medicine perspectives, discussed the role and mechanism of TCM compounds and monomeric components, and explored the research direction of using cutting-edge biotechnology to reveal the mechanism of oxaliplatin-induced neurotoxicity from a temporal-spatial perspective of intercellular communication and the application prospects of an interdisciplinary model combining TCM pathogenesis, western medicine manifestations, and artificial intelligence in precise intervention decision-making for TCM, aiming to provide research ideas for the prevention and treatment of oxaliplatin-induced neurotoxicity and the development of new drugs.

Comparative studies of immobilized polysaccharide derivatives chiral stationary phases for enantioseparation of furanocoumarins and dihydroflavones and discussion on chiral recognition mechanism.

Enantiomeric separation of furanocoumarins and dihydroflavones compounds were systematically studied in the normal-phase mode using four different polysaccharide-type chiral stationary phases, namely, Chiralpak IA, Chiralpak IC, Chiralpak IG, and Chiralpak IK-3 by high-performance liquid chromatography. The effect of alcohol modifiers and alcohol content on enantiomeric separation was evaluated for the separation of furanocoumarins and dihydroflavones. All the eight compounds have achieved baseline separation with the resolutions ranging between 1.52 and 23.11. For a better insight into the enantiorecognition mechanisms, thermodynamic analysis was carried out. The mechanisms of chiral recognition have been discussed. Among four chiral columns, Chiralpak IG exhibited the most universal and the best enantioseparation ability toward furanocoumarins and dihydroflavones when used n-hexane-isopropanol and n-hexane-ethanol as mobile phase, respectively. The steric hindrance, hydrogen bonding, and π-π interaction played major roles in chiral recognition on Chiralpak IG. By comparing four chiral columns, this work systematically analyzed the separation methods of furanocoumarins and dihydroflavones for the first time and reported some active chiral ingredients of traditional Chinese medicine that have never been separated, which provided a further insight into the enantioseparation of furanocoumarins and dihydroflavones on chiral stationary phases.

A practical method for rapid discrimination of constituents in Psoraleae Fructus by UPLC-Q-Orbitrap MS.

Psoraleae Fructus (PF) is one of the most frequently used traditional Chinese medicine, which has good efficacy in warming kidney to activate yang, promoting inspiration to relieve asthma and warming spleen to stop diarrhea. However, the chemical composition of PF is complex, which makes it difficult to determine its active and toxic components. In order to rapidly classify and identify the chemical components of the extracts from PF, this research was processed with CNKI, PubMed, and PubChem databases and data post-processing technique basing on ultrahigh performance liquid chromatography quadrupole orbitrap mass spectrometry (UPLC-Q-Orbitrap MS) technique. Finally, 73 chemical components were discriminated, including 44 flavonoids, 18 coumarins, and 11 terpenoids, with the cleavage rules of each chemical component summarized. This study established a UPLC-Q-Orbitrap MS method for the separation and discrimination of the chemical constituents of PF, which can lay a foundation for the further study of its medicinal substances and quality control.

Brain-Targeting Emodin Mitigates Ischemic Stroke via Inhibiting AQP4-Mediated Swelling and Neuroinflammation.

Failure to achieve target-specific delivery to ischemic brain sites has hampered the clinical efficacy of newly developed therapies for ischemic stroke. Emodin, an active ingredient isolated from traditional Chinese medicine, has been indicated to alleviate ischemic stroke; however, the underlying mechanism remains unclear. In this study, we aimed to achieve brain-targeted delivery of emodin to maximize its therapeutic efficacy and elucidate the mechanisms by which emodin alleviates ischemic stroke. A polyethylene glycol (PEG)/cyclic Arg-Gly-Asp (cRGD)-modified liposome was used to encapsulate emodin. TTC, HE, Nissl staining, and immunofluorescence staining were employed to evaluate the therapeutic efficacy of brain-targeting emodin in MCAO and OGD/R models. Inflammatory cytokine levels were determined using ELISA. Immunoprecipitation, immunoblotting, and RT-qPCR were utilized for clarifying the changes in key downstream signaling. Lentivirus-mediated gene restoration was employed to verify the core effector of emodin for relieving ischemic stroke. Encapsulating emodin in a PEG/cRGD-modified liposome enhanced its accumulation in the infarct region and substantially raised its therapeutic efficacy. Furthermore, we demonstrated that AQP4, the most abundant water transporter subunit expressed in astrocytes, plays a crucial role in mediating the mechanisms by which emodin inhibits astrocyte swelling, neuroinflammatory blood-brain barrier (BBB) breakdown in vivo and in vitro, and brain edema in general. Our study unveiled the critical target of emodin responsible for alleviating ischemic stroke and a localizable drug delivery vehicle in the therapeutic strategy for ischemic stroke and other brain injuries.

Time-dependent laxative effect of sennoside A, the core functional component of rhubarb, is attributed to gut microbiota and aquaporins.

ETHNOPHARMACOLOGICAL RELEVANCE: Sennoside A is a natural anthraquinone component mainly derived from rhubarb and has been routinely used as a clinical stimulant laxative. However, long-term application of sennoside A may lead to drug resistance and even adverse reactions, thus limiting its clinical use. Therefore, to reveal the time-dependent laxative effect and potential mechanism of sennoside A is of critical importance. AIM OF THE STUDY: This study was conducted to investigate the time-dependent laxative effect of sennoside A and unveil its underlying mechanism from the perspective of gut microbiota and aquaporins (AQPs). MATERIALS AND METHODS: Based on a mouse constipation model, 2.6 mg/kg sennoside A was administered orally for 1, 3, 7, 14 and 21 days, respectively. The laxative effect was assessed by the fecal index and fecal water content, the histopathology of the small intestine and colon was evaluated by hematoxylin-eosin staining. Gut microbiota changes was observed by 16S rDNA sequencing, and colonic AQPs expression was analyzed by quantitative real-time polymerase chain reaction and western blotting. Partial least-squares regression (PLSR) was used to screen out the effective indicators contributing to the laxative effect of sennoside A. The effective indicators were then fitted to time by a drug-time curve model to analyze the trend of efficacy of sennoside A, and the optimal time of administration was derived by comprehensive analysis with a three-dimensional (3D) time-effect image. RESULTS: Sennoside A had a significant laxative effect at 7 days of administration with no pathological changes in the small intestine or colon; however, at 14 or 21 days of administration, the laxative effect diminished and slight damage to the colon was observed. Sennoside A affects the structure and function of gut microbes. The alpha diversity showed that the abundance and diversity of gut microorganisms reached the highest value after 7 days of administration. Partial least squares discriminant analysis showed that the composition of the flora was close to normal when administered for less than 7 days, but was closest to the composition of constipation over 7 days. The expression of aquaporin 3 (AQP3) and aquaporin 7 (AQP7) decreased gradually after the administration of sennoside A, with the lowest expression at 7 days, and then increased gradually afterwards, while the expression of aquaporin 1 (AQP1) was the opposite. The PLSR results showed that AQP1, AQP3, Lactobacillus, Romboutsia, Akkermansia and UCG_005 contributed more to the laxative effect of the fecal index, and after fitting with the drug-time curve model, each index showed a trend of increasing and then decreasing. The comprehensive evaluation of the 3D time-effect image concluded that the laxative effect of sennoside A reached its best after 7 days of administration. CONCLUSION: Sennoside A should be used in regular dosages for less than one week, as it provides significant relief of constipation and exhibits no colonic damage within 7 days of administration. In addition, Sennoside A exerts its laxative effect by regulating gut microbiota of Lactobacillus Romboutsia, Akkermansia and UCG_005 and water channels of AQP1 and AQP3.

The experience of diabetic retinopathy patients during hospital-to-home full-cycle care: A qualitative study.

BACKGROUND: Diabetic retinopathy (DR) is one of the major blinding eye diseases worldwide. Psychological, emotional and social problems of DR patients are prominent. The aim of this study is to explore the experiences of patients with different phases of DR from hospital to home based on the "Timing It Right" framework, and to provide a reference for formulating corresponding intervention strategies. METHODS: The phenomenological method and semi-structured interviews were used in this study. A total of 40 patients with DR in different phases were recruited from a tertiary eye hospital between April and August 2022. Colaizzi's analysis method was used to analyse the interview data. RESULTS: Based on the "Timing It Right" framework, different experiences in five phases of DR before and after Pars Plana Vitrectomy (PPV) were extracted. The patients experienced complicated emotional reactions and inadequate coping skills during the pre-surgery phase, increased uncertainty during the post-surgery phase, insufficient confidence and the decision to change during the discharge preparation phase, eagerness for professional support and moving forward in exploration during the discharge adjustment phase, and courageous acceptance and positive integration during the discharge adaptation phase. CONCLUSION: The experiences of DR patients with vitrectomy in different phases of disease are ever-changing, and medical staff should provide personalized support and guidance to help DR patients get through the hard times smoothly and enhance the quality of hospital-family holistic care.

Pueraria protein extract inhibits melanogenesis and promotes melanoma cell apoptosis through the regulation of MITF and mitochondrial­related pathways.

Pueraria Lobata Radix (P. Lobata Radix) is an edible traditional Chinese medicine that contains various active compounds. Proteins from P. Lobata Radix have become the subject of increased interest in recent years. In evaluating the whitening effect on the skin, the present study found that the P. Lobata Radix water­soluble total protein extract (PLP) had the strongest inhibitory effect on tyrosinase activity. In the present study, the anti­melanogenic effect of PLP and the inhibitory effect on B16 melanoma cells were investigated. PLP significantly reduced the tyrosinase activity and melanin content in B16 melanoma cells. Mechanistically, PLP inhibited melanogenesis by decreasing the expression of tyrosinase, tyrosinase­related protein (TRP)­1 and TRP­2 through downregulation of the microphthalmia­associated transcription factor (MITF) gene, which was mediated by inhibition of p38 mitogen­activated protein kinase signaling. In addition, PLP inhibited cell viability and triggered apoptosis of B16 cells in a dose­dependent manner. Exposure to PLP reduced the mitochondrial membrane potential (MMP) and decreased ATP generation, leading to mitochondria­related apoptosis of B16 melanoma cells. The expression levels of succinate dehydrogenase (SDH) and its two related subunits (SDHA and SDHB) were downregulated significantly by PLP, which may be associated with the regulation of mitochondrial energy metabolism by PLP. These results may explain why MMP collapse and reduced ATP generation were observed in B16 melanoma cells treated with PLP. Finally, the present study demonstrated that the inhibition of melanin synthesis by PLP was correlated with the regulation of antioxidant enzymes to reduce reactive oxygen species levels. These results suggested that PLP inhibits melanogenesis by downregulating the expression of MITF­related melanogenic enzymes and triggering apoptosis through mitochondria­related pathways.

Cimifugin suppresses type 2 airway inflammation by binding to SPR and regulating its protein expression in a non-enzymatic manner.

BACKGROUND: Cimifugin is one of the main bioactive components of Yu-Ping-Feng-San, a well-known traditional Chinese medicine, which can effectively relieve Allergic asthma (AA) and atopic dermatitis and reduce recurrence in clinic. However, the underlying mechanism of cimifugin on AA is still unknown. PURPOSE: In the present study, we aimed to investigate the effect and mechanism of cimifugin on AA. STUDY DESIGN: In vivo and in vitro experimental studies were performed. METHODS: The effect of cimifugin on AA was demonstrated in vivo and in vitro. Sepiapterin reductase (SPR) was predicted as the most potent target of cimifugin in treating AA by reverse docking. Molecular docking and microscale thermophoresis (MST) were used to analyze the direct binding between cimifugin and SPR. Overexpression and interference of SPR were performed to verify whether targeting SPR is a key step of cimifugin in the treatment of AA. QM385, an inhibitor of SPR, was administrated in vivo and in vitro to evaluate the role of SPR in AA. Further, HPLC and cell-free direct hSPR enzyme activity assay were performed to research whether cimifugin regulated SPR by influencing the enzyme activity. Simultaneously, the inhibitors of protein degradation were used in vitro to explore the mechanism of cimifugin on SPR. RESULTS: We found cimifugin effectively alleviated AA by reducing airway hyperresponsiveness, inhibiting type 2 cytokines-mediated airway inflammation, and restoring the expression of epithelial barrier proteins. Molecular docking predicted the direct binding ability of cimifugin to SPR, which was further verified by MST. Notably, the therapeutic effect of cimifugin on AA was dampened with SPR interfering, in contrast, the phenotypic features of AA were significantly alleviated with QM385 application both in vivo and in vitro. Interestingly, cimifugin showed no effect on the enzyme activity of SPR, as the level of its substrate sepiapterin was not affected with cimifugin treatment by cell-free enzyme activity assay. Furthermore, we found cimifugin could reduce SPR protein expression without affecting its mRNA expression probably through autophagosome pathway. CONCLUSIONS: To our knowledge, we're reporting for the first time that cimifugin can suppresses type 2 airway inflammation to alleviate AA by directly binding to SPR and regulating its protein expression in a non-enzymatic manner.

Phytochemicals, Biological Activities, Molecular Mechanisms, and Future Prospects of Plantago asiatica L.

Plantago asiatica L. has been used as a vegetable and nutritious food in Asia for thousands of years. According to recent phytochemical and pharmacological research, the active compositions of the plant contribute to various health benefits, such as antioxidant, anti-inflammatory, antibacterial, antiviral, and anticancer. This article reviews the 87 components of the plant and their structures, as well as their biological activities and molecular research progress, in detail. This review provides valuable reference material for further study, production, and application of P. asiatica, as well as its components in functional foods and therapeutic agents.

A three-dimensional integration strategy for Q-markers identification: Taken Euphorbia Pekinensis Radix as an example.

Euphorbia Pekinensis Radix (EPR) is an important antitumor medicinal resource. However, quality control of EPR has not been well established due to the lack of quality markers (Q-markers) research. In this study, a three-dimensional integration strategy was developed to systematically characterize Q-markers and this method was successfully applied to identify Q-markers of EPR. Firstly, three core quality attributes-effectiveness, testability and specificity-were considered as three dimensions, and the weights of each dimension were calculated by analytical hierarch process. Then, the values of each dimension were evaluated by multi-indicators. For EPR with antitumor activity, cytotoxic assay and network pharmacology, UPLC analysis and literature search, compound belonging search were employed to calculate the values of effectiveness, testability and specificity, respectively. Finally, the weights and values were multiplied as the scores of each component on that dimension, and the total scores of the three dimensions were further integrated based on the radar plot and expressed as regression area, by which Q-markers were quantified and visualized. Five components were identified as Q-markers of EPR due to their high-ranked antitumor capacity, ease of measurement and excellent specificity, which laid an important foundation for the quality control improvement of EPR. Furthermore, the integrated strategy summarized here is helpful for the quantitative identification of Q-markers and promote the quality standard of traditional Chinese medicine.

Adverse effects of triclosan on kidney in mice: Implication of lipid metabolism disorders.

Triclosan (TCS) is a ubiquitous antimicrobial used in daily consumer products. Previous reports have shown that TCS could induce hepatotoxicity, endocrine disruption, disturbance on immune function and impaired thyroid function. Kidney is critical in the elimination of toxins, while the effects of TCS on kidney have not yet been well-characterized. The aim of the present study was to investigate the effects of TCS exposure on kidney function and the possible underlying mechanisms in mice. Male C57BL/6 mice were orally exposed to TCS with the doses of 10 and 100 mg/(kg•day) for 13 weeks. TCS was dissolved in dimethyl sulfoxide (DMSO) and diluted by corn oil for exposure. Corn oil containing DMSO was used as vehicle control. Serum and kidney tissues were collected for study. Biomarkers associated with kidney function, oxidative stress, inflammation and fibrosis were assessed. Our results showed that TCS could cause renal injury as was revealed by increased levels of renal function markers including serum creatinine, urea nitrogen and uric acid, as well as increased oxidative stress, pro-inflammatory cytokines and fibrotic markers in a dose dependent manner, which were more significantly in 100 mg/(kg•day) group. Mass spectrometry-based analysis of metabolites related with lipid metabolism demonstrated the occurrence of lipid accumulation and defective fatty acid oxidation in 100 mg/(kg•day) TCS-exposed mouse kidney. These processes might lead to lipotoxicity and energy depletion, thus resulting in kidney fibrosis and functional decline. Taken together, the present study demonstrated that TCS could induce lipid accumulation and fatty acid metabolism disturbance in mouse kidney, which might contribute to renal function impairment. The present study further widens our insights into the adverse effects of TCS.

[Quantitative identification of Q-markers of Euphorbiae Humifusae Herba based on AHP-CRITIC comprehensive weighting method].

This study investigated the quality markers(Q-markers) of Euphorbiae Humifusae Herba based on the analytic hierarchy process(AHP)-criteria importance through intercriteria correlation(CRITIC) comprehensive weighting method. The Q-markers evaluation system was constructed based on the AHP-CRITIC comprehensive weighting method with quantitative identification of Q-markers of Euphorbiae Humifusae Herba as the target layer. The index weights of the factor layer and the control layer were integrated based on the weights of three indicators(effectiveness, testability, and specificity) in the factor layer calculated by the AHP method and weights of eight indicators(anti-inflammatory inhibitory rate, coagulation shortening rate, anti-cancer inhibition rate, component degree value, component test batch, component average content, content variation coefficient, and number of medicinal materials retrieved according to components) in the control layer calculated by the CRITIC method. The comprehensive score of the chemical components of Euphorbiae Humifusae Herba was weighted and ranked to identify the Q-markers of Euphorbiae Humifusae Herba. In terms of comprehensive scores, top 10 potential Q-markers of Euphorbiae Humifusae Herba were ranked as cynaroside > quercetin > gallic acid > apigenin > luteolin > apigenin-7-O-glucoside > quercetin-7-O-glucoside > ellagic acid > astragalin > ethyl gallate. This study provides a reference for the quality control of Euphorbiae Humifusae Herba and a methodological reference for the quantitative identification of Q-markers of Chinese medicine.

Integrated dose-response metabolomics with therapeutic effects and adverse reactions may demystify the dosage of traditional Chinese medicine.

BACKGROUND: Traditional Chinese medicine (TCM) has been used to treat various diseases for thousands of years. However, the uncertainty of dosage as well as the lack of systemic evaluation of pharmacology and toxicology is one major reason why TCM remains mysterious and is not accepted worldwide. Hence, we aimed to propose an integrated dose-response metabolomics strategy based on both therapeutic effects and adverse reactions to guide the TCM dosage in treatment. METHODS: The proposed methodology of integrated dose-response metabolomics includes four steps: dose design, multiple comparison of metabolic features, response calculation and dose-response curve fitting. By comparing the changes of all metabolites under different doses and calculating these changes through superposition, it is possible to characterize the global disturbance and thus describe the overall effect and toxicity of TCM induced by different doses. Rhubarb, commonly used for constipation treatment, was selected as a representative TCM. RESULTS: This developed strategy was successfully applied to rhubarb. The dose-response curves clearly showed the efficacy and adverse reactions of rhubarb at different doses. The rhubarb dose of 0.69 g/kg (corresponding to 7.66 g in clinic) was selected as the optimal dose because it was 90% of the effective dose and three adverse reactions were acceptable in this case. CONCLUSION: An integrated dose-response metabolomics strategy reflecting both therapeutic effects and adverse reactions was established for the first time, which we believe is helpful to uncover the mysterious veil of TCM dosage. In addition, this strategy benefits the modernization and internationalization of TCM, and broadens the application of metabolomics.

Traditional Chinese Medicine: A promising strategy to regulate inflammation, intestinal disorders and impaired immune function due to sepsis.

Sepsis is described as a dysregulation of the immune response to infection, which leads to life-threatening organ dysfunction. The interaction between intestinal microbiota and sepsis can't be ignored. Furthermore, the intestinal microbiota may regulate the progress of sepsis and attenuate organ damage. Thus, maintaining or restoring microbiota may be a new way to treat sepsis. Traditional Chinese medicine (TCM) assumes a significant part in the treatment of sepsis through multi-component, multi-pathway, and multi-targeting abilities. Moreover, TCM can prevent the progress of sepsis and improve the prognosis of patients with sepsis by improving the imbalance of intestinal microbiota, improving immunity and reducing the damage to the intestinal barrier. This paper expounds the interaction between intestinal microbiota and sepsis, then reviews the current research on the treatment of sepsis with TCM, to provide a theoretical basis for its clinical application.

A Randomized Controlled Trial Evaluating the Effect of Tai Chi on the Drug Craving in Women.

This study was conducted in the purpose of investigating the effect of Tai Chi on drug craving for women with drug disorders. One hundred and twelve women were recruited from a drug rehabilitation center in China, and 47 and 48 were finally analyzed in the control group and exercise group, respectively. The exercise group underwent a 3-month Tai Chi training, whereas the control group experienced no exercise intervention during the same time period. The drug craving was measured by the visual analog scale. In data analysis, repeated-measures were utilized to test the differences between the control and exercise group over the course of the experiment time. The mean of the craving score significantly dropped from pre-test (control: mean = 5.38, SD = 3.04; exercise: mean = 4.68, SD = 2.93) to post-test (control: mean = 4.03, SD = 2.73; exercise: mean = 1.91, SD = 1.90) in both groups (control group: t = 3.84, df = 46, p < 0.001; exercise group: t = 5.941, df = 47, p < 0.001), with more decrease witnessed in the exercise group. Repeated-measures analysis with a Huynh-Feldt correction showed the significant effect of time (F = 27.383, p < 0.001) as well as the study group by time interaction (F = 3.52, p = 0.024). Tai Chi can ameliorate the drug craving in women and it could be a supportive treatment for drug addiction.

Huanglian ointment alleviates eczema by maintaining the balance of c-Jun and JunB and inhibiting AGE-RAGE-mediated pro-inflammation signaling pathway.

BACKGROUND: Huanglian ointment exhibits clinical efficacy for repairing skin barriers and inhibiting skin inflammation, and has been used to ameliorate eczema for many years. However, the active components and mechanism of Huanglian ointment have not yet been elucidated. PURPOSE: This study aimed to demonstrate the main active components and molecular mechanisms of Huanglian ointment for the treatment of eczema. METHODS: The main active components of Huanglian ointment were identified by gas chromatography-mass spectrometry. Network pharmacology approach and molecular docking techniques to predict the potential molecular mechanisms of Huanglian ointment alleviating eczema. Furthermore, Biostir-AD®-induced guinea pigs and tumor necrosis α (TNF-α)/interferon γ (IFN-γ)-induced HaCaT cells were employed to investigate the effectiveness and mechanisms of Huanglian ointment using histopathological staining, enzyme-linked immunosorbent assay, MTT assay, and western blot analysis. RESULTS: Fourteen chemistry components were identified in Huanglian ointment. In total, 78 intersecting gene targets were identified between Huanglian ointment and eczema, including Jun, inflammatory regulators, and chemokine factors. Intersecting gene targets were enriched for cytokine and chemokine receptor binding, and inflammatory related signaling pathways. The molecular docking results showed that the identified components had a stable binding conformation with core targets. In vivo experiments showed that Huanglian ointment markedly ameliorated eczema-like skin lesions, restored histopathological morphology, and decreased levels of TNF-α, IFN-γ, and interleukin 6. Moreover, Huanglian ointment effectively protected HaCaT cells against TNF-α/IFN-γ-induced cell death and overproduction of thymus- and activation-regulated chemokine, macrophage-derived chemokine, and regulated upon activation normal T cell-expressed and secreted factor. Subsequently, we found that Huanglian ointment repaired skin barriers by affecting c-Jun, JunB, and filaggrin expression, and suppressed inflammatory response by inhibiting AGE-RAGE signaling pathway, both in vivo and in vitro. CONCLUSION: Our results demonstrated that Huanglian ointment repaired skin barriers and inhibited inflammation by maintaining the balance of c-Jun and JunB, and suppressing AGE-RAGE signaling pathway, thereby relieving eczema. These findings providing a molecular basis for treatment of eczema by Huanglian ointment.