[Analysis of clinical research features and outcome indexes of traditional Chinese medicine intervention in septic kidney injury].

This study aims to systematically review the clinical features and outcome indicators in randomized controlled trial(RCT) of traditional Chinese medicine(TCM) intervention in septic kidney injury and provide a reference for optimizing clinical study design and building the core outcome set(COS) of TCM treatment of septic kidney injury. Computer searches were conducted on PubMed, Cochrane Library, EMbase, Web of Science, CNKI, Wanfang, VIP, and SinoMed to find published RCT of TCM intervention in septic kidney injury in the past five years, extract the basic characteristics, intervention measures, outcome indicators, and other data of included studies, and conduct descriptive analysis. 53 RCTs were included, and the sample size was mostly concentrated in 60-80 cases, with abdominal infection being the most common(15 articles, 83.3%) and the TCM syndrome of blood stasis being the most frequent(9 articles, 50.0%). The frequency of intervention methods from high to low were TCM decoction(28 articles, 52.8%), Chinese patent medicine(22 articles, 41.5%), and combined TCM therapy(3 articles, 7.5%); the intervention time of the trial was more than 7 d(34 articles, 69.4%). The risk of bias in included studies was unclear. A total of 84 outcome indicators were involved, which were divided into 9 fields, including 63 physical and chemical tests(305 times, 72.2%), 4 kinds of disease degree(48 times, 11.6%), 4 kinds of clinical effective rate(15 times, 3.6%), 1 kind of quality of life(1 time, 0.2%), 2 kinds of economic evaluation(14 times, 3.3%), 1 kind of TCM disease(9 times, 2.1%), 2 kinds of long-term prognosis(16 times, 3.8%), 2 kinds of safety events(6 times, 1.4%), and 5 other indicators(8 times, 0.7%). The cumulative frequency was 422 times, among which the outcome indicators with higher frequency were inflammatory factors(42 articles, 79.2%) and markers of renal function and kidney injury(40 articles, 75.5%). Only 1(1.9%) of the included articles mentioned primary and secondary outcome indicators, and 6 articles(11.3%) mentioned safety events, 13 articles(24.5%) mentioned economic assessment. The RCT quality of TCM intervention in septic renal injury was generally low, and the reference standards for sepsis, kidney injury, and TCM syndrome diagnosis were not uniform. There are some problems in outcome indicators, such as unclear distinction between primary and secondary indicators, neglect of endpoint indicators, lack of application of TCM characteristic indicators, and insufficient attention to safety events and economic assessment. It is suggested that the quality of clinical research methodology should be improved in the future, and the COS should be constructed to provide high-level evidence-based evidence for TCM intervention in septic kidney injury.

Warming enhances the negative effects of shrub removal on phosphorus mineralization potential.

Shrubs have developed various mechanisms for soil phosphorus utilization. Shrub encroachment caused by climate warming alters organic phosphorus mineralization capability by promoting available phosphorus absorption and mediating root exudates. However, few studies have explored how warming regulates the effects of dominant shrubs on soil organic phosphorus mineralization capability. We provide insights into warming, dominant shrub removal, and their interactive effects on the soil organic phosphorus mineralization potential in the Qinghai-Tibetan Plateau. Real-time polymerase chain reaction was used to quantify the soil microbial phosphatase genes (phoC and phoD), which can characterize the soil organic phosphate mineralization potential. We found that warming had no significant effect on the soil organic phosphate-mineralized components (total phosphate, organic phosphate, and available phosphate), genes (phoC and phoD), or enzymes (acid and alkaline phosphatases). Shrub removal negatively influenced the organic phosphate-mineralized components and genes. It significantly decreased soil organic phosphate mineralization gene copy numbers only under warming conditions. Warming increased fungal richness and buffered the effects of shrub removal on bacterial richness and gene copy numbers. However, the change in the microbial community was not the main factor affecting organic phosphate mineralization. We found only phoC copy number had significant correlation to AP. Structural equation modelling revealed that shrub removal and the interaction between warming and shrub removal had a negative direct effect on phoC copy numbers. We concluded that warming increases the negative effect of shrub removal on phosphorus mineralization potential, providing a theoretical basis for shrub encroachment on soil phosphate mineralization under warming conditions.

Effect of electroacupuncture on global cerebral ischemia-reperfusion injury in rats: A urine proteome analysis.

BACKGROUND: This study aimed to investigate dynamic urinary proteome changes of electroacupuncture (EP) on cerebral ischemia-reperfusion (CI/R) injured rats and to explore the therapeutic biological mechanisms of EP. METHODS: First, changed urinary proteins were found in EP stimulation in healthy rats. Then, we used a CI/R injury rat model induced by Pulsinelli's four-vessel occlusion (4-VO) method to explore the function of EP on urinary proteome in CI/R injury. Urine samples were collected for proteome analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and bioinformatics analysis. RESULTS: In total, 384 proteins were identified, among which 47 proteins (23 upregulated, 24 downregulated) were differentially expressed with 0.6-log FC and p < .05. Gene ontology analysis revealed that the cell redox homeostasis, acute-phase response, response to lipopolysaccharide, and cellular response to glucocorticoid stimulus were significantly enriched. The partially biologically connected differential proteins were found by the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis in the EP group. With the CI/R rat model, 80 proteins (27 upregulated, 53 downregulated) were significantly changed in the CI/R rats compared to the controls. Among these differentially expressed proteins (DEPs), 23 proteins (17 upregulated, six downregulated) showed significant changes after EP treatment (0.6-log FC change, p < .05). The main related biological processes were aging, immune response, acute-phase response, liver regeneration, protein catabolic process, and response to oxidative stress. Many metabolic pathways were enriched by KEGG analysis. CONCLUSION: Our results indicate that the EP could alleviate cerebral damage induced by ischemia-reperfusion through an anti-inflammatory and metabolism regulation mechanism. The urinary proteome might reflect the pathophysiological changes in EP pretreatment in the treatment and prevention of CI/R injury.

The Role of Zuo Jin Wan in Modulating the Tumor Microenvironment of Colorectal Cancer.

INTRODUCTION: Traditional Chinese medicine (TCM) can modulate the immune function of tumor patients in various ways. Zuojin Wan (ZJW, a 6:1 ratio of Huanglian and Wuzhuyu) can modulate the microenvironment of ulcerative colitis, but its role in regulating the CRC microenvironment remains unclear. Exploring the role of ZJW in CRC immunomodulation may improve the antitumor effect of existing immunotherapeutic strategies. MATERIAL AND METHODS: The active compounds of each herb in ZJW were obtained from the HIT2.0 database with literature evidence. Single-cell RNA sequencing data of CRC were obtained from published studies (PMID: 32451460, 32103181, and 32561858). Pathway enrichment was analyzed using the reactome database, and intergenic correlation analysis was performed using the corrplot R software package. ZJW-regulated gene expression was verified by RT-qPCR. RESULTS: Huanglian and Wuzhu contain 19 and 4 compounds, respectively. Huang Lian targets 146 proteins, and Wu Zhu Yu targets 28 proteins based on evidence from the literature. ZJW regulates a range of biological processes associated with immune function, including cytokine signaling and Toll-Like Receptor 4 (TLR4) cascade. ZJW regulates malignant CRC cells, immune cells (including T-cells, B-cells, mast cells, NK/NKT cells, and myeloid cells), and other non-immune cells (including endothelial cells, enteric glial cells, and pericytes). We confirmed that ZJW significantly downregulated the expression of TIMP1 and MTDH. CONCLUSIONS: ZJW regulates a range of cells in the CRC microenvironment, including malignant CRC, immune cells, and stromal cells. In CRC cell lines, downregulation of TIMP1 and MTDH by ZJW may play an important role in the immunomodulation in CRC.

Exploration of material basis: Chemical composition profile, metabolic profile and pharmacokinetic characteristics in Xingbei Zhike granule.

HEADINGS ETHNOPHARMACOLOGICAL RELEVANCE: Xingbei Zhike granule (XBZK), a widely prescribed Chinese patent medicine, is known for its efficacy in clearing lung qi, relieving cough and reducing phlegm, as well as fever, dry and bitter taste, and irritability. Despite its clinical popularity, comprehensive investigations into its chemical composition, in vivo metabolism, and pharmacokinetic characteristics are limited. AIM OF THE STUDY: This study investigates the chemical composition, in vivo metabolism, and in vivo dynamics of XBZK to clarify its material basis and pharmacokinetic characteristics. MATERIALS AND METHODS: Ultra-high performance liquid chromatography with Orbitrap tandem mass spectrometry (UPLC-Orbitrap-MS) was used to determine the chemical composition and in vivo metabolic profile of XBZK. Additionally, UPLC with triple quadrupole mass spectrometry (UPLC-TQ-MS/MS) was performed to quantify its main components and evaluate its in vivo dynamics in rat plasma. RESULTS: In total, 57 components were identified in XBZK. Furthermore, 40 prototype components and 31 metabolites were detected in various biological matrices of rats, including plasma, tissues, bile, feces, and urine. After administration, the area under the curve (AUC) for ephedrine (Eph), pseudoephedrine (Peph), neotuberostemonine (Neo), amygdalin (Amy), and enoxolone (Eno) exhibited a strong linear relationship with the administered dose (r > 0.9) in all rats. And gender-related differences in the absorption of peiminine (Pmn), peimisine (Pms), and chrysin-7-O-glucuronide (Cog) were notable among rats, with male rats showing a dose-dependent pattern of absorption, while female rats exhibited minimal absorption. CONCLUSIONS: XBZK contains 57 components, primarily composed of flavonoids, alkaloids, and coumarins. The eight main components were rapidly absorbed and eliminated, with some, such as Eph, Peph, Neo, Amy and Eno, following a linear pharmacokinetic pattern. Furthermore, Pmn, Pms and Cog were well absorbed in male rats, showing a dose-dependent behavior.

Mechanism of effects of electroacupuncture on memory and cognitive impairment in offspring rats with perinatal nicotine exposure. / ç”µé’ˆå¯¹å›´äº§æœŸå°¼å¤ä¸æš´éœ²å­ä»£å¤§é¼ è®°å¿†å’Œè®¤çŸ¥æŸä¼¤å½±å“çš„æœºåˆ¶æŽ¢è®¨.

OBJECTIVES: To observe the effects of electroacupuncture(EA) on memory, cognitive impairment, and the brain-derived neurotrophic factor(BDNF)/N-methyl-D-aspartate receptor subtype 1(NMDAR1) pathway in the brains of offspring rat with intrauterine growth restriction(IUGR) induced by perinatal nicotine exposure(PNE), so as to explore the underlying mechanism. METHODS: SD rats were randomly divided into normal, model, and EA groups, with 4 mothers and 10 offspring rats of each mother in each group. The IUGR model was established by subcutaneous injection of nicotine during pregnancy and lactation. From the 6th day of pregnancy in the mothers until the 21st day after birth of the offspring rats, EA (2 Hz/15 Hz, 1 mA) was administered bilaterally at the "Zusanli"(ST36) of mothers, once daily for 20 min. The brain organ coefficient was used to evaluate the brain development of the offspring rats. The Y-maze test and novel object recognition experiments were performed to assess memory and cognitive function. HE staining was used to observe the development and cellular morphology of the hippocampus and prefrontal cortex in the offspring rats. UV spectrophotometry was used to measure the glutamate(Glu) content in the hippocampus. ELISA was used to detect the BDNF content in the hippocampus. Western blot was performed to measure the protein expression of NMDAR1 in the hippocampus. Immunohistochemistry was used to count the number of BDNF-positive cells in the hippocampus and prefrontal cortex. RESULTS: Compared with the normal group, the brain organ coefficient, exploration time of the novel arm, spontaneous alternation rate, and novel object recognition index, contents of BDNF and expression of NMDAR1 proteins in the hippocampus, the number of BDNF-positive cells in the CA1 and CA3 regions of the hippocampus and prefrontal cortex were significantly reduced(P<0.01), while the Glu content in the hippocampus was significantly increased(P<0.01) in the model group of offspring rats；decreased cell number, scattered arrangement, and disrupted cellular structure were observed in the hippocampus and prefrontal cortex of offspring rats in the model group. Compared with the model group, the brain organ coefficient, exploration time of the novel arm, spontaneous alternation rate, and novel object recognition index, the BDNF contents and NMDAR1 protein expression in the hippocampus, the number of BDNF-positive cells in the hippocampal CA1 and CA3 regions and prefrontal cortex significantly increased(P<0.01, P<0.05), while the Glu content in the hippocampus was significantly decreased (P<0.01) in offspring rats of the EA group；increased cell number, neat arrangement, and reduced cellular damage were observed in the hippocampus and prefrontal cortex in the EA group. CONCLUSIONS: EA has an improving effect on memory and cognitive function impairment in offspring rats with IUGR induced by PNE, and this mechanism may be associated with the regulation of BDNF/NMDAR1 pathway, thereby improving the neuronal quantity and structure of the hippocampus and prefrontal cortex in offspring rats.

Further Refinement is Required for Patient-Reported Outcome Scales for Respiratory Diseases Based on Traditional Chinese Medicine Theory for Applicability.

Objective: To summarize the contents and assess the methodological quality and measurement properties of the patient-reported outcome (PRO) scales featured with Traditional Chinese Medicine (TCM) for respiratory diseases based on the guideline of COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN). Methods: PubMed, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), Wanfang Data, VIP, and China Biology Medicine (CBM) were searched for studies on PRO scales featured with TCM for respiratory diseases from their inception until December 2022. The characteristics of the PRO scales were qualitatively summarized. Following the COSMIN guideline, the risk of bias was assessed according to the checklist, and different measurement properties (content validity, structural validity, internal consistency, reliability, criterion validity, and responsiveness) were evaluated. Finally, the evidence's overall quality was assessed, and the recommendation was formulated using the modified GRADE approach. Results: A total of 13 scales were included, with 6 for chronic obstructive pulmonary disease (COPD), 3 for lung cancer, 2 for idiopathic pulmonary fibrosis (IPF), 1 for community-acquired pneumonia (CAP), and 1 for bronchiectasis. All 13 scales are disease-specific scales and were developed based on Chinese cultural background to measure the efficacy of TCM. The study did not provide information on measurement error, cross-cultural validity, and hypothesis testing for the construct validity of these measures. No scale was rated as sufficient in content validity and responsiveness. Two scales showed sufficient structural validity, while 11 scales exhibited sufficient internal consistency. Three scales demonstrated sufficient reliability, and 7 scales showed sufficient criterion validity. All 13 scales have a recommendation level of B. Conclusion: The 13 scales could reflect the clinical efficacy of TCM and are suitable for the Chinese population. Nevertheless, the validation of these scales was not comprehensive enough, and the methodological quality of their studies needs to be further strengthened.

Acupuncture Relieves Cervical Spondylosis Radiculopathy by Regulating Spinal Microglia Activation Through MAPK Signaling Pathway in Rats.

Purpose: Local acupuncture has been found to have a good analgesic effect in rats with cervical spondylosis radiculopathy (CSR), but it lacks a regulatory effect on traditional Chinese medicine syndrome types of CSR. We proposed "Invigorating Qi and activating Blood" (IQAB) acupuncture, compared with Fenbid, and local electroacupuncture (LEA), to observe whether it has advantages in the protection of the CSR rat model and to elucidate its mechanism through the MAPK (mitogen-activated protein kinase) signaling pathway. Materials and Methods: Male Sprague-Dawley rats were randomly divided into six groups: control, sham, model, Fenbid, LEA, and IQAB. The CSR model was induced by inserting nylon sutures to compress the C4-T1 nerve root. The Fenbid group was treated with ibuprofen sustained-release capsules (15 mg/kg·d, ig). The LEA group received electroacupuncture at both C5 and C7 EX-B2 once a day. The IQAB group received acupuncture at both ST36 and BL17 based on the LEA group's intervention. Mechanical allodynia and gait, morphological changes in the spinal cord, IL-6 and TNF-α levels, MAPKs phosphorylation ratio, monocyte chemoattractant protein-1 (MCP-1) levels in the spinal cord, and the expression of p-p38 in the spinal cord and its colocalization with neurons and glial cell activation markers were detected. Results: Mechanical allodynia, gait disorder, edema, reduced Nissl-positive cell numbers, and increased IL-6 and TNF-α levels in the spinal cord were observed in CSR rats. IQAB significantly alleviated these changes, and the effects were generally comparable to those of Fenbid. Meanwhile, the phosphorylation ratios of p38 and extracellular regulated protein kinase (ERK), co-expression of p-p38 with neuron/microglia, and MCP-1 levels in the spinal cord were markedly down-regulated by IQAB compared with those in CSR model rats. Conclusion: IQAB reduced p38-activation-related microglia activation and MCP-1 levels, thus alleviating pathological changes, inflammation levels in the local spinal cord, and pain behavior of CSR.

Evidence for Wnt signaling's central involvement in perinatal nicotine exposure-induced offspring lung pathology and its modulation by electroacupuncture.

OBJECTIVE: Many factors during pregnancy can induce intrauterine growth restriction (IUGR), resulting in various adverse perinatal outcomes such as low birth weight and multiple organ disorders. Among these factors, prenatal smoke/nicotine exposure is a common cause of IUGR, often associated with altered fetal lung development. The classical Wnt signaling pathway plays a vital role in lung development, and its alterations are commonly associated with developmental lung pathologies. The purpose of this study was to determine whether electroacupuncture (EA) at "Zusanli" (ST 36) points protects perinatal nicotine exposure (PNE)-induced offspring lung dysplasia through Wnt/ß-catenin signaling pathway and to identify specific Wnt signaling pathway targets of EA. METHODS: Following a well-established protocol, nicotine (1 mg/kg/ body weight) was administered subcutaneously to pregnant Sprague Dawley rat dams from gestational day 6 to postnatal day 21. In the EA group, dams were treated with EA at both ST 36 acupoints, while in another experimental group, Wnt/ß-catenin signaling pathway agonist was injected subcutaneously (2 mg/kg/ body weight). Offspring body weight (PND 1, 7, 14, and 21), lung weight, Wnt signaling markers, pulmonary function, and lung morphology were determined at sacrifice on PND 21. Specifically, Western blotting and Real-time PCR were used to detect the protein and mRNA levels of critical Wnt signaling markers Wnt2, Wnt7b, FZD4, FZD7, LRP5, and LRP6 in the offspring lung. The protein levels of ß-catenin in lung tissue of offspring rats were detected by ELISA that of LEF-1 by Western blotting. RESULTS: Compared to the control group, the body and lung weights of the offspring rats were significantly decreased in the nicotine-only exposed group. The pulmonary function determined as FVC, PEF, TV, and Cdyn was also significantly decreased, while PIF was significantly increased. The protein levels and mRNA expression of Wnt2, Wnt7b, FZD4, FZD7, LRP5, and LRP6 in the lung tissue of the PNE offspring rats were significantly increased. With EA administration at ST 36 acupoints concomitant with nicotine administration, the body and lung weights, pulmonary function (FVC, PEF, PIF, TV, and Cdyn), protein and mRNA levels Wnt signaling pathway markers (Wnt2, Wnt7b, FZD4, FZD7, LRP5, LRP6, ß-catenin, and LEF-1) normalized and were not different from the control group. Notably, Wnt agonists agonist administration blocked the protective effects of EA against PNE-induced lung morphological, molecular, and function changes, highlighting the central significance of Wnt pathway signaling in PNE-induced offspring pulmonary pathology and its modulation by EA at ST 36 acupoints. CONCLUSION: Concomitant maternal EA at ST 36 acupoints from gestational day 6 to PND 21 protects against offspring PNE-induced lung phenotype. The protective effect is achieved by regulating the expression of Wnt ligand proteins (Wnt2 and Wnt7b) and receptor proteins (FZD4, FZD7, LRP5, and LRP6) upstream of the Wnt/ß-catenin signaling pathway intermediates ß-catenin, and LEF-1.

An Immunomodulatory Hydrogel by Hyperthermia-Assisted Self-Cascade Glucose Depletion and ROS Scavenging for Diabetic Foot Ulcer Wound Therapeutics.

Current therapeutic protocols for diabetic foot ulcers (DFUs), a severe and rapidly growing chronic complication in diabetic patients, remain nonspecific. Hyperglycemia-caused inflammation and excessive reactive oxygen species (ROS) are common obstacles encountered in DFU wound healing, often leading to impaired recovery. These two effects reinforce each other, forming an endless loop. However, adequate and inclusive methods are still lacking to target these two aspects and break the vicious cycle. This study proposes a novel approach for treating DFU wounds, utilizing an immunomodulatory hydrogel to achieve self-cascade glucose depletion and ROS scavenging to regulate the diabetic microenvironment. Specifically, AuPt@melanin-incorporated (GHM3) hydrogel dressing is developed to facilitate efficient hyperthermia-enhanced local glucose depletion and ROS scavenging. Mechanistically, in vitro/vivo experiments and RNA sequencing analysis demonstrate that GHM3 disrupts the ROS-inflammation cascade cycle and downregulates the ratio of M1/M2 macrophages, consequently improving the therapeutic outcomes for dorsal skin and DFU wounds in diabetic rats. In conclusion, this proposed approach offers a facile, safe, and highly efficient treatment modality for DFUs.

Polygalae Radix Oligosaccharide Esters May Relieve Depressive-like Behavior in Rats with Chronic Unpredictable Mild Stress via Modulation of Gut Microbiota.

Polygalae radix (PR) is a well-known traditional Chinese medicine that is used to treat depression, and polygalae radix oligosaccharide esters (PROEs) are the main active ingredient. Although gut microbiota are now believed to play key role in depression, the effects of PROEs on depression via modulation of gut microbiota remain unknown. In this article, we investigate the effect of PROEs on the gut microbiota of a depression rat and the possible mechanism responsible. The depression rat model was induced by solitary rearing combined with chronic unpredictable mild stress (CUMS). The depression-like behavior, the influence on the hypothalamic-pituitary-adrenal (HPA) axis, the contents of monoamine neurotransmitter in the hippocampus, and the quantity of short-chain fatty acids (SCFAs) in the feces were each assessed, and the serum levels of lipopolysaccharide (LPS) and interleukin-6 (IL-6) were measured by ELISA. Additionally, ultrastructural changes of the duodenal and colonic epithelium were observed under transmission electron microscope, and the gut microbiota were profiled by using 16S rRNA sequencing. The results show that PROEs alleviated the depression-like behavior of the depression model rats, increased the level of monoamine neurotransmitters in the brain, and reduced the hyperfunction of the HPA axis. Furthermore, PROEs regulated the imbalance of the gut microbiota in the rats, relieving intestinal mucosal damage by increasing the relative abundance of gut microbiota with intestinal barrier protective functions, and adjusting the level of SCFAs in the feces, as well as the serum levels of LPS and IL-6. Thus, we find that PROEs had an antidepressant effect through the restructuring of gut microbiota that restored the function of the intestinal barrier, reduced the release of intestinal endotoxin, and constrained the inflammatory response.

Trabecular Bone Score as a More Sensitive Tool to Evaluate Bone Involvement in MEN1-related Primary Hyperparathyroidism.

CONTEXT: The skeletal involvement of multiple endocrine neoplasia type 1-related primary hyperparathyroidism (MHPT) is not exactly the same as that of sporadic primary hyperparathyroidism (SHPT). Trabecular bone score (TBS) as a texture parameter has been reported to reflect trabecular bone damage. OBJECTIVE: This study aimed to compare the clinical characteristics, especially the skeletal involvement, between patients with MHPT and SHPT. METHODS: The clinical characteristics were retrospectively collected in 120 patients with MHPT and compared with 360 patients with SHPT in the same period. Dual-energy X-ray absorptiometry were conducted in some patients with MHPT, in whom bone mineral density (BMD) and calculated TBS derived from lumbar spine dual-energy X-ray absorptiometry images were compared with those of patients with SHPT. RESULTS: Although the duration of disease in the MHPT group was longer, the age at hospital visit was significantly lower than that in the SHPT group (43.5 [interquartile range, 31.5-52.0] vs 52.0 [interquartile range, 40.5-61.0], P < .001). The proportion of skeletal involvement in the MHPT group was significantly lower. However, in the subgroup of MHPT cases (n = 86) with data of BMD, there was no significant difference in skeletal involvement from SHPT cases matched for gender and age. Although the BMD and TBS in the lumbar spines of patients with MHPT were lower than those of patients with SHPT (BMD: 0.91 ± 0.18 g/cm2 vs 1.01 ± 0.17 g/cm2; TBS: 1.22 ± 0.14 vs 1.29 ± 0.11, P < .001). According to TBS, among 34 patients with MHPT with normal BMD, 15 patients had bone microstructure damage. CONCLUSION: The cancellous bone microarchitecture was more severely damaged in patients with MHPT according to TBS, which suggested that TBS could be a sensitive supplemental index in addition to BMD to identify bone-involvement risk in patients with MHPT.

Triterpenoids of Ganoderma lucidum inhibited S180 sarcoma and H22 hepatoma in mice by regulating gut microbiota.

In order to explore effect of natural plant extracts on anti-tumor and prevent tumor development. The study assessed the antitumor effect of triterpenoids of Ganoderma lucidum (TGL) on S180 and H22 tumor bearing mice. A triterpene compound, 2α, 3α, 23-trihydroxy-urs-12-en-28-oic acid, was successfully isolated and purified from G. lucidum. S180 and H22 cells were subcutaneously inoculated in the left axilla of mice to establish a transplantable tumor model. After, the mice were orally treated with TGL and evaluated by tumor inhibition rate, organ index, and the serum index. The Bax and Bcl-2 proteins and gut microbiota was analyzed using western blot and 16S rDNA sequencing respectively. The results showed the tumor inhibition rates of TGL were higher than 40% in H22 and S180 tumor bearing mice. TGL had a protective effect on the spleen and thymus, and improved lipid peroxidation caused by the increased free radicals. TGL downregulated Bcl-2 and upregulated Bax. In particular, TGL treatment improved the reduction of gut microbiota richness and structure.

Tubson-2 decoction ameliorates rheumatoid arthritis complicated with osteoporosis in CIA rats involving isochlorogenic acid A regulating IL-17/MAPK pathway.

BACKGROUND: Osteoporosis (OP) is considered as one of the major comorbidities of rheumatoid arthritis (RA), and is responsible for fragility fracture. However, there is currently no effective treatment for RA complicated with OP. Tubson-2 decoction (TBD), a Mongolian medicine also known as Erwei Duzhong Decoction, has been shown to exert a preventive effect on post-menopausal osteoporosis (PMOP). The preventive effects of TBD on RA-induced OP, as well as the bioactive compound responsible and the underlying mechanisms, remain to be elucidated. OBJECTIVE: To explore the effects of TBD on RA-induced OP in vivo, and to elucidate the mechanism of isochlorogenic acid A (ICA), the effective component of TBD, in vitro. METHODS: To evaluate the anti-arthritic and anti-osteoporotic effects of TBD, we conducted H&E straining and safranine O/fast green, TEM, immunohistochemistry (IHC), bone histomorphometry, micro-CT imaging, and biomechanical testing in collagen induced arthritis (CIA) rats. The active ingredient in TBD was identified using network pharmacology and molecular docking. The identification was supported by in vivo IHC assay, and further confirmed using qRT-PCR, Western blot, and SEM analysis in TNF-α-treated MH7A cells and/or in LPS-exposed RAW264.7 cells. RESULTS: Oral administration of TBD attenuated the severity of arthritis and osteopenia as well as poor bone quality, in CIA rats. Additionally, TBD and the positive control, tripterygium glycosides (TG), exhibited similar effects in reducing inflammation in both the synovium and ankle joint. They also were both effective in improving bone loss, microarchitecture, and overall bone quality. TBD reduced the expression of MMP13, IL-17, and p-JNK protein in the synovium of CIA rats. ICA, which was screened, suppressed TNF-α or LPS-triggered inflammatory responses via down-regulating IL-17 signaling, involving in MMP13, IL-1ß, IL-23, and IL-17, and the MAPK pathway including p-ERK, p-JNK, and p-P38, both in MH7A cells and in RAW264.7 cells. Furthermore, ICA prevented osteoclasts from differentiating and bone resoprtion in a dose-dependent manner in vitro. CONCLUSION: This study provides the first evidence that TBD exerts intervening effects on RA-induced OP, possibly through the downregulation of the IL-17/MAPK signaling pathway by ICA. The findings of our study provides valuable insights for further research in this area.

Comparative pharmacokinetics of six bioactive components of Shen-Wu-Yi-Shen tablets in normal and chronic renal failure rats based on UPLC-TSQ-MS/MS.

ETHNOPHARMACOLOGICAL RELEVANCE: Shen-Wu-Yi-Shen tablets (SWYST), a Chinese patent medicine consisting of 12 herbal medicines, was formulated by a famous TCM nephrologist, Zou Yunxiang. It is clinically used to improve the symptoms of nausea, vomiting, poor appetite, dry mouth and throat, and dry stool in patients with chronic renal failure (CRF) accompanied by qi and yin deficiency, dampness, and turbidity. SWYST can reduce urea nitrogen, blood creatinine, and urinary protein loss, and increase the endogenous creatinine clearance rate. However, little is known about its pharmacokinetics. AIM OF STUDY: To compare the pharmacokinetics of six bioactive components after oral administration of SWYST in normal and adenine-induced CRF rats. MATERIALS AND METHODS: A method based on ultra-performance liquid chromatography coupled with a triple-stage quadrupole mass spectrometer (UPLC-TSQ-MS/MS) was developed and validated to determine the six bioactive compounds (albiflorin, paeoniflorin, plantagoguanidinic acid, rhein, aloe-emodin, and emodin) in rat plasma. Rat plasma samples were prepared using protein precipitation. Chromatography was performed on an Agilent Eclipse Plus C18 column (3.0 × 50 mm, 1.8 µm) using gradient elution with a mobile phase composed of acetonitrile and water containing 0.1% (v/v) formic acid, while detection was achieved by electrospray ionization MS under the multiple selective reaction monitoring modes. After SWYST administration, rat plasma was collected at different time points, and the pharmacokinetic parameters of six analytes were calculated and analyzed based on the measured plasma concentrations. RESULTS: The UPLC-TSQ-MS/MS method was fully validated for its satisfactory linearity (r ≥ 0.9913), good precisions (RSD <11.5%), and accuracy (RE: -13.4∼13.1%), as well as acceptable limits in the extraction recoveries, matrix effects, and stability (RSD <15%). In normal rats, the six analytes were rapidly absorbed (Tmax ≤ 2 h), and approximately 80% of their total exposure was eliminated within 10 h. Moreover, in normal rats, the AUC0-t and Cmax of albiflorin, plantagoguanidinic acid, and rhein exhibited linear pharmacokinetics within the dose ranges, while that of paeoniflorin is non-linear. However, in CRF rats, the six analytes exhibited reduced elimination and significantly different AUC or Cmax values. These changes may reflect a decreased renal clearance rate or inhibition of drug-metabolizing enzymes and transporters in the liver and gastrointestinal tract caused by CRF. CONCLUSIONS: A sensitive UPLC-TSQ-MS/MS method was validated and used to investigate the pharmacokinetics of SWYST in normal and CRF rats. This is the first study to investigate the pharmacokinetics of SWYST, and our findings elucidate the causes of their different pharmacokinetic behaviors in CRF rats. Furthermore, the results provide useful information to guide further research on the pharmacokinetic-pharmacodynamic correlation and clinical application of SWYST.

Discovery of the material basis of Jiuwei Xifeng granules using pharmaco-chemistry and pharmacokinetics.

ETHNOPHARMACOLOGICAL RELEVANCE: Jiuwei Xifeng granules (JWXF) is primarily used for the treatment of Tourette syndrome (TS) with kidney-Yin deficiency and internal stirring of liver wind. However, few studies have focused on this issue. AIM OF THE STUDY: This study aimed to clarify chemical composition of JWXF using in vitro and in vivo pharmaco-chemistry and to provide a basis for the clinical use of JWXF using a strategy of pharmacokinetics. MATERIALS AND METHODS: In this study, the chemical constituents and in vivo metabolism of JWXF were evaluated using high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF-MS/MS), and the time-dependent processes of the three main components in rats were detected using ultra-high performance liquid chromatography-triple quadrupole mass spectrometry (UPLC-QQQ-MS/MS). RESULTS: A total of 75 constituents were identified, including 22 alkaloids, 21 terpenes, 15 organic acids and their derivatives, and 17 other compounds. After administration, 12 compounds were identified in rat plasma, including 11 prototypes and one metabolite. Pharmacokinetic analysis showed that the effects of gentiopicroside, gastrodin, and sweroside in rats were dose-dependent when the dose of JWXF was 1-4 g/kg. They were rapidly absorbed and did not accumulate in the plasma after 7-day continuous intragastric administration. CONCLUSIONS: JWXF consists of 75 components, including alkaloids, terpenes, and organic acids. The three main compounds, gastrodin, gentiopicroside, and sweroside, undergo rapid absorption, elimination, and dose-dependent pharmacokinetics.

Safety Evaluation of Curcumol by a Repeated Dose 28-Day Oral Exposure Toxicity Study in Rats.

Curcumol, a natural product isolated from the traditional Chinese medicine Rhizoma curcumae, possesses various potential therapeutic values in many diseases. However, evidence of its toxicological profile is currently lacking. In this study, a repeated toxicity study of curcumol was conducted for the first time. SD rats were exposed to doses of 250, 500, 1000 mg/kg in a selected dose formulation for 28 days through oral administration. The potential toxic effects of curcumol on the blood system were observed and further validated in vivo and in vitro. Moreover, other hematology and biochemistry parameters as well as the weight of organs were altered, but no related histopathological signs were observed, indicating these changes were not regarded as toxicologically relevant. Our current findings provide a complete understanding of the safety profile of curcumol, which may contribute to its further study of investigational new drug application.

The tissue distribution of Jinzhen oral liquid in healthy and influenza mice.

Jinzhen oral liquid (JZOL) is widely used in China. However, its tissue distribution, a vital part of the efficacy substances research, has not been reported yet. This study characterized its chemical components and its prototypes and metabolites in mice, and investigated its tissue distribution in pathological and healthy mice. Several constituents were characterized, including 55 constituents in JZOL, 11 absorbed prototypes and six metabolites in plasma and tissues. The metabolic pathways were demethylation, dehydration and acetylation. A sensitive, accurate and stable quantitative method was established and applied to the tissue distribution. After administration of JZOL, these seven components were rapidly distributed to various tissues, mainly staying in the small intestine, and less distributed to lung, liver and kidney. Compared with healthy mice, the absorption of baicalin, wogonoside, rhein, glycyrrhizic acid and liquiritin apioside was reduced in influenza mice, but their elimination was slow. However, influenza infection had no obvious effect on the overall distribution of the most important components (baicalin, glycyrrhizic acid and wogonoside) in the plasma or small intestine, but obviously affected the distribution of baicalin in liver. In summary, seven components are rapidly distributed to various tissues, and influenza infection has certain influence on the tissue distribution of JZOL.

Application of attenuation coefficient in the assessment of hepatic involvement in children and adolescents with Wilson's disease.

BACKGROUND: To investigate whether the attenuation coefficient (ATT) can be used as a noninvasive index to assess liver involvement in children and adolescents with Wilson's disease (WD). METHODS: Children and adolescents diagnosed with WD were retrospectively collected from the First Affiliated Hospital of the Anhui University of Traditional Chinese Medicine between May 2022 and August 2022. The findings on ATT, Shear Wave Measurement (SWM), AST to platelet ratio index (APRI), and fibrosis 4 (FIB-4) score were obtained. The liver involvement of WD was classified into 3 groups based on serum levels of collagen type IV (CIV), hyaluronic acid (HA), laminin (LN) and precollagen type III N-terminal peptide (PIIINP): (1) Group1 (n = 25), no abnormalities in CIV, HA, LN and PIIINP; (2) Group2 (n = 19), elevation of 1 or 2 indexes in CIV, HA, LN, and PIIINP; Group3 (n = 18), elevation of 3 or 4 indicators in CIV, HA, LN, and PIIINP. The levels of ATT, SWM, APRI and FIB-4 were compared between the 3 groups; and correlation of ATT with SWM and triglyceride (TG) was performed using Spearman's correlation analysis. The Receiver operating characteristic (ROC) curve was used to analyze the diagnostic efficacy of ATT alone and its combination with SWM, APRI, and FIB-4 in children and adolescents with WD. RESULTS: A total of 62 children and adolescents with WD were retrospectively retrieved. ATT levels were significantly different in intergroup comparisons (P < 0.001). The ROC curve showed that the area under the curve (AUC) for the diagnosis of hepatic steatosis using ATT was 0.714, 0.712 and 0.867 in Group 1 versus Group 2, Group 2 versus Group 3, and Group 1 versus Group 3, respectively; the sensitivity for the diagnosis of hepatic steatosis in Group 1 versus Group 2 was 89.47% with the cutoff value of ATT of 0.73 dB/cm/MHz. No significant correlation found between ATT and TG (ρ = 0.154, P = 0.231). Compared to ATT alone, the combination of ATT with APRI and FIB-4 or the combination of ATT with SWM, APRI, and FIB-4 showed a better diagnostic efficacy in Group 1 versus Group 2 (both P = 0.038). CONCLUSION: ATT could be used as a non-invasive index for the evaluation of liver steatosis in children and adolescents with WD, with a good clinical applicative value. Furthermore, ATT in combination with APRI, FIB-4, and SWM might have better diagnostic efficacy than ATT alone.

An innovative strategy to control Microcystis growth using tea polyphenols sustained-release particles: preparation, characterization, and inhibition mechanism.

Allelochemicals have been shown to inhibit cyanobacterial blooms for several years. In view of the disadvantages of "direct-added" mode, natural and pollution-free tea polyphenolic allelochemicals with good inhibitory effect on cyanobacteria were selected to prepare sustained-release particles by microcapsule technology. Results showed that the encapsulation efficiency of tea polyphenols sustained-release particles (TPSPs) was 50.6% and the particle size ranged from 700 to 970 nm, which reached the nanoscale under optimum preparation condition. Physical and chemical properties of TPSPs were characterized to prove that tea polyphenols were well encapsulated and the particles had good thermal stability. The optimal dosage of TPSPs was determined to be 0.3 g/L, at which the inhibition rate on Microcystis aeruginosa in logarithmic growth period could be maintained above 95%. Simultaneous decrease in algal density and chlorophyll-a content indicated that the photosynthesis of algal cells was affected leading to cell death. Significant changes of antioxidant enzyme activities suggested that Microcystis aeruginosa's antioxidant systems had been disrupted. Furthermore, TPSPs increased the concentration of O2- which led to lipid peroxidation of cell membrane and a subsequent increase in malondialdehyde (MDA) content. Meanwhile, the protein content, nucleic acid content, and electrical conductivity in culture medium rose significantly indicating the cell membrane was irreversibly damaged. This work can provide a basis for the utilization of environmentally friendly algal suppressants.