[Mechanism of Guizhi Gancao Decoction against myocardial ischemia-reperfusion injury based on network pharmacology and experimental verification].

This study employed network pharmacology to investigate the effect of Guizhi Gancao Decoction(GGD) on myocardial ischemia-reperfusion injury(MI/RI) in rats and decipher the underlying mechanism. Firstly, the chemical components and targets of GGD against MI/RI were searched against the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), SwissTargetPrediction, and available articles. STRING and Cytoscape 3.7.2 were used to establish the protein-protein interaction(PPI) network for the common targets, and then Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses were carried out for the core targets. The "drug-active component-target-pathway" network was built. Furthermore, molecular docking between key active components and targets was conducted in AutoDock Vina. Finally, the rat model of MI/RI was established, and the myocardial infarction area was measured. Hematoxylin-eosin(HE) staining and transmission electron microscopy(TEM) were employed to detect cardiomyocyte pathology and ultrastructural changes. Western blot was employed to determine the expression of related proteins in the myocardial tissue. A total of 75 chemical components of GGD were screened out, corresponding to 318 targets. The PPI network revealed 46 core targets such as tumor protein p53(TP53), serine/threonine kinase 1(AKT1), signal transducer and activator of transcription 3(STAT3), non-receptor tyrosine kinase(SRC), mitogen-activated protein kinase 1(MAPK1), MAPK3, and tumor necrosis factor(TNF). According to GO and KEGG enrichment analyses, the core targets mainly affected the cell proliferation and migration, signal transduction, apoptosis, and transcription, involving advanced glycation end products-receptor(AGE-RAGE), MAPK and other signaling pathways in cancers and diabetes complications. The molecular docking results showed that the core components of GGD, such as licochalcone A,(+)-catechin, and cinnamaldehyde, had strong binding activities with the core target proteins, such as MAPK1 and MAPK3. The results of animal experiments showed that compared with the model group, GGD significantly increase superoxide dismutase, decreased malondialdehyde, lactate dehydrogenase, and creatine kinase-MB, and reduced the area of myocardial infarction. HE staining and TEM results showed that GGD pretreatment restored the structure of cardiomyocytes and alleviated the pathological changes and ultrastructural damage of mitochondria in the model group. In addition, GGD significantly down-regulated the phosphorylation of c-Jun N-terminal kinase and p38 and up-regulate that of extracellular regulated kinases 1/2 in the myocardial tissue. The results suggested that GGD may exert the anti-MI/RI effect by regulating the MAPK signaling pathway via the synergistic effects of Cinnamomi Ramulus and Glycyrrhizae Radix et Rhizoma.

Progress in clinical and basic research of fuzheng Huayu formula for the treatment of liver fibrosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine has great potential and advantages in the treatment of liver fibrosis, with Fuzheng Huayu formula (FZHY) serving as a prime example due to its remarkable efficacy in delaying and reversing liver fibrosis while simultaneously improving clinical symptoms for patients. AIM OF THE REVIEW: In this paper, we present a comprehensive review of recent studies on the therapeutic potential of FZHY and its components/ingredients in the treatment of liver fibrosis and cirrhosis, with the aim of providing insights for future research endeavors. MATERIALS AND METHODS: A comprehensive literature search was conducted on FZHY, TCM319, traditional Chinese medicine 319, liver fibrosis and cirrhosis using multiple internationally recognized databases including PubMed, Embase, Springer, Web of science, SciVerse ScienceDirect, Clinical Trails. Gov, CNKI, Wanfang, and VIP. RESULTS: FZHY is widely used clinically for liver fibrosis and cirrhosis caused by various chronic liver diseases, with the effects of improving serum liver function, liver pathological histology, serological indices related to liver fibrosis, decreasing liver stiffness values and portal hypertension, as well as reducing the incidence of hepatocellular carcinoma and morbidity/mortality in patients with cirrhosis. Numerous in vivo and in vitro experiments have demonstrated that FZHY possesses anti-fibrotic effects by inhibiting hepatic stellate cell activation, reducing inflammation, protecting hepatocytes, inhibiting hepatic sinusoidal capillarization and angiogenesis, promoting extracellular matrix degradation, and facilitating liver regeneration. In recent years, there has been a growing focus on investigating the primary active components/ingredients of FZHY, and significant strides have been made in comprehending their synergistic mechanisms that enhance efficacy. CONCLUSION: FZHY is a safe and effective drug for treating liver fibrosis. Future research on FZHY should focus on its active components/ingredients and their synergistic effects, as well as the development of modern cocktail drugs based on its components/ingredients. This will facilitate a more comprehensive understanding of the molecular mechanisms and targets of FZHY in treating liver fibrosis, thereby further guide clinical applications and drug development.

Trans-3, 5, 4'-trimethoxystilbene restrains non-small-cell lung carcinoma progression via suppressing M2 polarization through inhibition of m6A modified circPACRGL-mediated Hippo signaling.

BACKGROUND: Non-small-cell lung carcinoma (NSCLC) accounts for ∼85% of all lung carcinomas. Trans-3,5,4'-trimethoxystilbene (TMS) shows strong anti-tumor activity and induces tumor cell apoptosis. However, its function and mechanism in NSCLC still require investigation. METHODS: PMA was used to treated THP-1 cells for macrophage differentiation. The abundance and m6A modification of circPACRGL were examined with qRT-PCR and MeRIP. Colony forming, transwell, wound healing, and Western blotting assays were applied to analyze proliferation, invasion, migration, and EMT. Macrophage polarization was determined through flow cytometry analysis of M1 and M2 markers. The interplay between circPACRGL, IGF2BP2 and YAP1 was validated by RNA pull-down and RIP assays. Mice received subcutaneous injection of NSCLC cells as a mouse model of subcutaneous tumor. RESULTS: CircPACRGL was upregulated in NSCLC cells, but it was reduced by TMS treatment. CircPACRGL depletion blocked proliferation, migration, and invasion in H1299 and H1975 cells. TMS suppressed these malignant behaviors, but it was abolished by circPACRGL overexpression. In addition, NSCLC-derived exosomes delivered circPACRGL into THP-1 cells to promote its M2 polarization, but TMS inhibited these effects by downregulating exosomal circPACRGL. Mechanically, exosomal circPACRGL bound to IGF2BP2 to improve the stability of YAP1 mRNA and regulate Hippo signaling in polarized THP-1 cells. TMS inhibited NSCLC growth via suppressing Hippo signaling and M2 polarization in vivo. CONCLUSION: TMS restrains M2 polarization and NSCLC progression by reducing circPACRGL and inhibiting exosomal circPACRGL-mediated Hippo signaling. Thus, these findings provide a novel mechanism underlying NSCLC progression and potential therapeutic targets.

Identification of Erzhu Jiedu Recipe and its molecular mechanism underlying inhibited human hepatoma cells by UHPLC-Q-Exactive Orbitrap HRMS and network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Erzhu Jiedu Recipe (EZJDR) is a formula of traditional Chinese medicine (TCM) for treating hepatitis B virus-related hepatocellular carcinoma (HBV-HCC). However, its effective components and the mechanism of action remain unclear. AIM OF THE STUDY: To explain how the active compounds of EZJDR suppress the growth of hepatoma cells. METHODS: UHPLC-Q-Exactive Orbitrap HRMS was used to identify the chemical constituents of EZJDR and their distribution in the serum and liver of mice. Together with experimental investigations, network pharmacology unraveled the molecular mechanism of components of EZJDR underlying the inhibited Hep3B cells. RESULTS: A total of 138 compounds which can be divided into 18 kinds of components (such as sesquiterpenoids, diterpenoids, anthraquinones, flavonoids and so on) were found in the aqueous extract of EZJDR. Of these components, the tricyclic-diterpenoids exhibited a highest exposure in the serum (74.5%) and liver (94.7%) of mice. The network pharmacology revealed that multiple components of EZJDR interacted with key node genes involved in apoptosis, proliferation, migration and metabolism through various signaling pathways, including ligand binding and protein phosphorylation. In vitro experiments demonstrated that 6 tricyclic-diterpenoids, 2 anthraquinones and 1 flavonoid inhibited the viability of Hep3B cells, with IC50 values ranging from 3.81 µM to 37.72 µM. Dihydrotanshinone I had the most potent bioactivity, arresting the S phase of cell cycle and inducing apoptosis. This compound changed the expression of proteins, including Bad, Bax, Bcl-2, Bal-x, caspase3 and catalase, which were associated with mitochondria-mediated apoptotic pathways. Moreover, dihydrotanshinone I increased the levels of p21 proteins, but decreased the phosphorylated p53, suggesting accumulation of p53 protein prevented cell cycle progression of Hep3B cells with damaged DNA. CONCLUSIONS: These results suggested that multiple components of EZJDR-diterpenoid, anthraquinone and flavonoid-could be the effective material for the treatment of HBV-HCC. This research provided valuable insights into the molecular mechanism of action underlying the therapeutic effects of EZJDR.

Schisantherin A protects hepatocyte via upregulating DDAH1 to ameliorate liver fibrosis in mice.

BACKGROUND: Hepatic fibrosis is the pivotal determinant in the progression of chronic liver diseases towards cirrhosis or advanced stages. Studies have shown that Schisantherin A (Sin A), the primary active compound from Schizandra chinensis (Turcz.) Baill., exhibits anti-hepatic fibrosis effects. However, the mechanism of Sin A in liver fibrosis remain unclear. PURPOSE: To examine the effects and underlying mechanism of Sin A on hepatic fibrosis. STUDY DESIGN AND METHODS: The effects and mechanism of Sin A were investigated using liver fibrosis mouse models induced by carbon tetrachloride (CCl4) or dimethylnitrosamine (DMN), as well as H2O2-induced hepatocyte injury in vitro. RESULTS: Sin A treatment ameliorated hepatocyte injury, inflammation, hepatic sinusoidal capillarization, and hepatic fibrosis in both CCl4-induced and DMN-induced mice. Sin A effectively reversed the reduction of DDAH1 expression, the p-eNOS/eNOS ratio and NO generation and attenuated the elevation of hepatic ADMA level induced by CCl4 and DMN. Knockdown of DDAH1 in hepatocytes not only triggered hepatocyte damage, but it also counteracted the effect of Sin A on protecting hepatocytes in vitro. CONCLUSION: Our findings indicate that Sin A ameliorates liver fibrosis by upregulating DDAH1 to protect against hepatocyte injury. These results provide compelling evidence for Sin A treatment in liver fibrosis.

Structural characterization of an inulin neoseries-type fructan from Ophiopogonis Radix and the therapeutic effect on liver fibrosis in vivo.

Ophiopogonis Radix is a well-known Traditional Chinese Medicine and functional food that is rich in polysaccharides and has fructan as a characteristic component. In this study, an inulin neoseries-type fructan designated as OJP-W2 was obtained and characterized from Ophiopogonis Radix, and its potential therapeutic effect on liver fibrosis in vivo were investigated. Structural studies revealed that OJP-W2 had a molecular weight of 5.76 kDa and was composed of glucose and fructose with a molar ratio of 1.00:30.87. Further analysis revealed OJP-W2 has a predominantly lineal (1-2)-linked ß-D-fructosyl units linked to the glucose moiety of the sucrose molecule with (2-6)-linked ß-D-fructosyl side chains. Pharmacological studies revealed that OJP-W2 exerted a marked hepatoprotective effect against liver fibrosis, the mechanism of action was involved in regulating collagen deposition (α-SMA, COL1A1 and liver Hyp contents) and TGF-ß/Smads signaling pathway, alleviating liver inflammation (IL-1ß, IL-6, CCL5 and F4/80) and MAPK signaling pathway, and inhibiting hepatic apoptosis (Bax, Bcl-2, ATF4 and Caspase 3). These data provide evidence for expanding Ophiopogonis Radix-acquired fructan types and advancing our understanding of the specific role of inulin neoseries-type fructan in liver fibrosis therapy.

Zhilong Huoxue Tongyu capsule alleviates myocardial fibrosis by improving endothelial cell dysfunction.

Background and aim: Zhilong Huoxue Tongyu (ZL) capsule is a classical traditional Chinese medicine (TCM) with satisfactory curative effects. Endothelial cell (EC) dysfunction plays an important role during myocardial fibrosis (MF). But the therapeutic effect of ZL capsule on EC dysfunction remains unknown in the development of MF. This study aims to investigate the effect of ZL capsule on EC dysfunction during MF in vivo. Experimental procedure: The model of MF is established in vivo by injecting isoproterenol for 14 days, simultaneously, we examined the therapeutic effect of ZL capsule on MF in vivo. An integrative approach combining biomarker examination, echocardiography and myocardial fibrosis condition using Hematoxylin-eosin staining, Masson staining, and Sirius red staining were performed to assess the efficacy of ZL capsule against MF. Subsequently, comprehensive immunofluorescence staining was performed to evaluate the therapeutic effect of ZL capsule on EC dysfunction. Results and conclusion: Prior to experiments, analysis of the published single-cell sequencing data was performed and it was discovered that EC dysfunction plays an important role. Further pharmacological results showed that ZL capsule could alleviate fibrosis injury and collagen fiber deposition. The mechanism investigation results showed that the endothelial-to-mesenchymal transition (EndMT) and MHC class-II (MHC-II) expression in EC were improved. In addition, ZL capsule can attenuate the inflammatory response during MF by intervening the activation of CD4+T cell mediated by EC. For the first time, we provided evidence that ZL capsule could improve MF by alleviating EC dysfunction via the regulation of EndMT and expression of MHC-II. Taxonomy classification by evise: Myocardial fibrosis, Chinese Herbal Medicine, Traditional Medicine, Endothelium, dysfunction, Endothelial-to-mesenchymal transition.

Recent progress on the application of compound formulas of traditional Chinese medicine in clinical trials and basic research in vivo for chronic liver disease.

ETHNOPHARMACOLOGICAL RELEVANCE: Chronic liver diseases mainly include chronic viral liver disease, metabolic liver disease, cholestatic liver disease (CLD), autoimmune liver disease, and liver fibrosis or cirrhosis. Notably, the compound formulas of traditional Chinese medicine (TCM) is effective for chronic liver diseases in clinical trials and basic research in vivo, which provide evidence of chronic liver disease treatment with integrated TCM and traditional Western medicine. AIM OF THE REVIEW: This paper aims to provide a comprehensive review of the compound formulas of TCM for treating different chronic liver diseases to elucidate the composition, main curative effects, and mechanisms of these formulas and research methods. MATERIALS AND METHODS: Different keywords related to chronic liver diseases and keywords related to the compound formulas of TCM were used to search the literature. PubMed, Scopus, Web of Science, and CNKI were searched to screen out original articles about the compound formulas of TCM related to the treatment of chronic liver diseases, mainly including clinical trials and basic in vivo research related to Chinese patent drugs, classic prescriptions, proven prescriptions, and hospital preparations. We excluded review articles, meta-analysis articles, in vitro experiments, articles about TCM monomers, articles about single-medicine extracts, and articles with incomplete or uncertain description of prescription composition. Plant names were checked with MPNS (http://mpns.kew.org). RESULTS: In this review, the clinical efficacy and mechanism of compound formulas of TCM were summarized for the treatment of chronic viral hepatitis, nonalcoholic fatty liver disease, CLD, and liver fibrosis or cirrhosis developed from these diseases and other chronic liver diseases. For each clinical trial and basic research in vivo, this review provides a detailed record of the specific composition of the compound formulas of TCM, type of clinical research, modeling method of animal experiments, grouping methods, medication administration, main efficacy, and mechanisms. CONCLUSION: The general development process of chronic liver disease can be summarized as chronic hepatitis, liver fibrosis or cirrhosis, and hepatocellular carcinoma. The compound formulas of TCM have some applications in these stages of chronic liver diseases. Owing to the continuous progress of medical technology, the benefits of the compound formulas of TCM in the treatment of chronic liver diseases are constantly changing and developing.

[Off-line comprehensive two-dimensional countercurrent chromatography-liquid chromatography separation of Curcuma volatile oil].

The chemical constituents of volatile oils used in traditional Chinese medicine are highly complex. Thus, achieving the complete separation of volatile oils by one-dimensional chromatography is difficult owing to the low peak capacity of the technique. Although comprehensive two-dimensional gas chromatography provides an efficient means for separating volatile oils, it cannot be used to screen bioactive components because of its limitations. Therefore, developing a new method to separate volatile oils based on liquid chromatography is of great significance in efforts to obtain new approaches to screen bioactive components in volatile oil. The objectives of the present study are to establish an efficient method for separating the chemical constituents of Curcuma volatile oil using off-line comprehensive two-dimensional countercurrent chromatography-liquid chromatography (CCC-LC) and to investigate the two-dimensional peak capacity, orthogonality, and spatial coverage of this method. Both CCC and LC conditions were optimized. A biphasic n-hexane-methanol-water solvent system was selected via the colorimetric method, and the lower phase was used as the mobile phase in gradient-elution mode: 0-55 min, n-hexane-methanol-water (5∶2∶3 v/v/v); 55-170 min, n-hexane-methanol-water (5∶3∶2, v/v/v); 170-290 min, n-hexane-methanol-water (5∶4∶1, v/v/v). After gradient elution, elution-extrusion elution mode was applied within 290-375 min. Good resolution was achieved by the CCC separation process. The HPLC separation process was carried out with gradient elution using a mobile phase composed of acetonitrile (A)-water (B): 0-10 min, 50%A-65%A; 10-14 min, 65%A; 14-21 min, 65%A-85%A; 21-25 min, 85%A-95%A; 25-30 min, 95%A-55%A; 30-40 min, 55%A. Curcuma volatile oil was separated under the above optimized two-dimensional separation conditions, and the data obtained were drawn into a two-dimensional contour map using Matlab software. The calculated total peak capacity exceeded 954, which was 10 times more than that of one-dimensional chromatography. High orthogonality (r=0.17) and spatial coverage factor (68.1%) were also obtained. Our research provides a new methodology for separating volatile oils used in traditional Chinese medicine as well as an approach for evaluating the quality of traditional Chinese medicinal herbs using two-dimensional chromatographic fingerprints.

A combined electrohydrodynamic atomization method for preparing nanofiber/microparticle hybrid medicines.

Bacterial prostatitis is a challenging condition to treat with traditional dosage forms. Physicians often prescribe a variety of dosage forms with different administration methods, which fail to provide an efficient and convenient mode of drug delivery. The aim of this work was to develop a new type of hybrid material incorporating both electrosprayed core-shell microparticles and electrospun nanofibers. A traditional Chinese medicine (Ningmitai, NMT) and a Western medicine (ciprofloxacin, CIP) were co-encapsulated within this material and were designed to be released in a separately controlled manner. Utilizing polyvinylpyrrolidone (PVP) as a hydrophilic filament-forming polymer and pH-sensitive Eudragit® S100 (ES100) as the particulate polymeric matrix, a combined electrohydrodynamic atomization (EHDA) method comprising coaxial electrospraying and blending electrospinning, was used to create the hybrids in a single-step and straightforward manner. A series of characterization methods were conducted to analyze both the working process and its final products. Scanning electron microscopy and transmission electron microscopy revealed that the EHDA hybrids comprised of both CIP-PVP nanofibers and NMT-ES100 core-shell microparticles. Multiple methods confirmed the rapid release of CIP and the sustained release of NMT. The antibacterial experiments indicated that the hybrids exhibited a more potent antibacterial effect against Escherichia coli dh5α and Bacillus subtilis Wb800 than either the separate nanofibers or microparticles. The amalgamation of fibrous nanomedicine and particulate micromedicine can expand the horizon of new types of medicines. The integration of electrospinning and coaxial electrospraying provides a straightforward approach to fabrication. By combining hydrophilic soluble polymers and pH-sensitive polymers in the hybrids, we can ensure the separate sequential controlled release of CIP and NMT for a potential synergistic and convenient therapy for bacterial prostatitis.

Tanshinone IIA alleviates atherosclerosis in LDLR-/- mice by regulating efferocytosis of macrophages.

Background: Tanshinone IIA (TIIA) is the major lipid-soluble active ingredient of the traditional Chinese medicine Salvia miltiorrhiza, which slows down atherosclerosis (AS). However, it remains unclear whether TIIA has the potential to enhance macrophage efferocytosis and thereby improve atherosclerosis. Objective: The focus of this examination was to determine if TIIA could reduce lipid accumulation and treat AS by enhancing efferocytosis. Methods: Firstly, we conducted in vivo experiments using LDLR knockout (LDLR-/-) mice for a period of 24 weeks, using histopathological staining, immunofluorescence and Western blot experiments to validate from the efficacy and mechanism parts, respectively; in addition, we utilized cells to validate our study again in vitro. The specific experimental design scheme is as follows: In vivo, Western diet-fed LDLR-/- mice for 12 weeks were constructed as an AS model, and normal diet-fed LDLR-/- mice were taken as a blank control group. The TIIA group and positive control group (atorvastatin, ATO) were intervened for 12 weeks by intraperitoneal injection (15 mg/kg/d) and gavage (1.3 mg/kg/d), respectively. In vitro, RAW264.7 cells were cultured with ox-LDL (50 ug/mL) or ox-LDL (50 ug/mL) + TIIA (20 uM/L or 40 uM/L). Pathological changes in aortic plaques and foam cell formation in RAW264.7 cells were evaluated using Masson and Oil Red O staining, respectively. Biochemical methods were used to detect lipid levels in mice. The immunofluorescence assay was performed to detect apoptotic cells and efferocytosis-related signal expression at the plaques. RT-qPCR and Western blot were carried out to observe the trend change of efferocytosis-related molecules in both mouse aorta and RAW264.7 cells. We also used the neutral red assay to assess RAW264.7 cells' phagocytic capacity. Results: Compared with the model group, TIIA decreased serum TC, TG, and LDL-C levels (p < 0.01), reduced the relative lumen area of murine aortic lipid-rich plaques (p < 0.01), enhanced the stability of murine aortic plaques (p < 0.01), reduced ox-LDL-induced lipid build-up in RAW264.7 cells (p < 0.01), and upregulated efferocytosis-related molecules expression and enhance the efferocytosis rate of ox-LDL-induced RAW264.7 cells. Conclusion: TIIA might reduce lipid accumulation by enhancing the efferocytosis of macrophages and thus treat AS.

Effects and potential mechanism of dietary vitamin C supplementation on hepatic lipid metabolism in growing laying hens under chronic heat stress.

The adverse effects of chronic heat stress (CHS)-induced fatty liver syndrome on laying hens during the egg-producing stages have been wildly documented. However, until nowadays, the CHS responses of growing laying hens as well as its alleviating effects of vitamin C are rarely reported. In this study, 12-wk-old laying hens were subjected to CHS at 36 °C for 10 h/d for 3 wk with or without dietary supplementation of 300 mg/kg vitamin C. Results showed that CHS significantly impaired the growth performances and the liver functions of birds, as characterized by reduced feed intake and body weight, increased hepatic lipid accumulation and serum concentrations of TG, ALT, and AST, as well as the abnormal expression patterns of the lipid metabolism-related genes. Vitamin C supplementation successfully mitigated the lipid accumulation, while showing no alleviating effect on the serum contents of ALT or AST, which are two key indicators of liver functions. Metabolomic analysis based on UPLC-Q-TOF/MS identified 173 differential metabolites from the HS and HSV group samples, and they are mainly enriched in the pathways related to the cellular components, vitamin and amino acid metabolism and energy substance metabolism. The results indicate that CHS-induced hepatic lipid deposition in growing laying hens is effectively alleviated by dietary supplementation of vitamin C, which is probably resulted from the alterations of hepatocellular metabolic patterns.

Chronic heat stress (CHS)-induced fatty liver syndrome (FLS) is one of the major problems faced in poultry industry. However, the heat stress response as well as the alleviating strategies for growing laying hens is rarely concerned until nowadays. In this study, 12-wk-old laying hens were subjected to the CHS condition with or without dietary supplementation of 300 mg/kg vitamin C, we found that CHS can also remarkably impair the growth performance and liver functions and induce the hepatic lipid metabolism disorders in the growing laying hens. Vitamin C supplementation successfully mitigated the hepatic lipid accumulation, while showed no alleviating effect on the liver functions. Metabolomic analysis further identified 173 differential metabolites between CHS and HSV groups, which are mainly enriched in the pathways including the cellular components, vitamin and amino acid metabolism and the energy substance metabolism. The results suggest that vitamin C supplementation can effectively alleviate the hepatic lipid deposition in growing laying hens under CHS probably through altering their energy metabolism patterns.

Improving soil phosphorus availability in saline areas by marine bacterium Bacillus paramycoides.

The utilization of phosphate-solubilizing bacteria (PSB) in agriculture has long been proposed as an eco-friendly method to enhance soil phosphorus (P) availability, thereby reducing reliance on chemical P fertilizers. However, their application in saline soils is challenged by salt-induced stress on common PSB strains. In this study, we sourced bacterial strains from marine environments, aiming to identify robust PSB strains adaptable to saline conditions and assess their potential as P bio-fertilizers through a microcosm experiment. Our findings indicate that the inoculation of a selected marine PSB, Bacillus paramycoides 3-1a, increased soil available P content by 12.5% when applied alone and by 61.2% when combined with organic amendments. This enhancement results from improved inorganic P solubilization and organic P mineralization in soils. Additionally, these treatments raised soil nitrogen levels, reshaped microbial community structures, and significantly enhanced wheat (Triticum aestivum L.) growth, with P accumulation increasing by 24.2-40.9%. Our results underscore the potential of marine PSB in conjunction with organic amendments for the amelioration of saline agricultural soils.

Management Quality of Surgical Instrument and Influence of Cleaning and Sterilization on the Surgical Outcomes of the Patient: A Review.

When a medical device or surgical instrument comes into contact with the patient's sterile tissue or mucous membrane during the various processes, the risk of introducing infections into the patient's body increases. Furthermore, an infection may be transmitted from one patient to another, from a patient to a member of the medical staff and vice versa or from the environment to the patient via improperly sterilized or disinfected equipment. A number of outbreaks and diseases have been documented in the hospital setting as a result of poorly sanitized devices. As a result, adequate disinfection procedures for medical and surgical items are required in all healthcare facilities. It is equally the responsibility of healthcare providers to reduce and eliminate such infections. Each hospital should have its own standards for sterilization and disinfection of equipment based on the intended use of medical devices and associated infections. In order to reduce the risk of both endogenous and exogenous infections, infection control procedures must be implemented in general practice. Using a formulation containing alcohol alone or in combination with other agents to properly wash hands after each patient's checkup and before any procedure reduces the likelihood of transmitting infections to and from patients. Sterilization and disinfection are the most important aspects of infection control. The most common sterilization methods are steam sterilizers and ethylene dioxide sterilizers. Trash generated during practice should be handled according to protocol and rules, as it may be a source of nosocomial infections. Trained personnel are required to carry out these procedures.

The effect of Baduanjin Qigong combined with five-elements music on anxiety and quality of sleep in asymptomatic patients with COVID-19 infection: A randomised controlled trial.

Background: Infections of Coronavirus Disease-2019 (COVID-19) and the subsequent quarantine can culminate in anxious mood and sleep disturbances. The objective of this clinical trial was to investigate the effect of traditional Qigong with music therapy on relieving anxiety and improving the quality of sleep in Chinese adults with COVID-19 infection. Methods: A total of 200 asymptomatic COVID-19 infected patients were randomly assigned into two groups during their quarantine period in Chongming Island, Shanghai. The patients in the treatment group daily received Baduanjin Qigong, five-elements music therapy and routine care, while the patients in the control group only took the routine care. The primary outcome was anxiety levels measured by the 7-item Generalized Anxiety Disorder scale (GAD-7). Secondary outcomes included the quality of sleep measured by the Jenkins Sleep Scale (JSS), the degree of depression measured by the Patient Health Questionnaire (PHQ-9), as well as the self-efficacy in the Perceived Health Competence Scale (PHCS). An online questionnaire was given to all participants on the day of arrival to determine the baseline for all outcomes and then given again on the day of discharge. A one-way analysis of covariance was used to analyze the differences between the two groups after intervention. Results: At the end of the intervention, 177 (88.5%) patients finished the questionnaire. Patients in the treatment group had clearly decreased GAD-7 scores (MD = 2.7, 95% CI = 2.3, 3.2) after the daily exercise and music. Patients in the control group had little changes in the GAD-7 (MD = -0.2, 95%CI = -0.7, 0.3, P = 0.07), as well as the PHQ-9 (MD = 0.1, 95%CI = -0.5, 0.6, P = 0.66) after the routine care, when compared to their baseline scores. There were statistical between-group differences in GAD-7 (MD = 2.9, 95% CI = 2.2, 3.6, P < 0.001）and in the PHQ-9 scores (MD = 3.6, 95% CI = 2.9, 4.4, P < 0.001) at the post-treatment. Compared with the control group, patients had significantly lower scores on the JSS (MD = 2.7, 95% CI = 2.0, 3.3, P < 0.001), and higher scores on the PHCS (MD = -5.0, 95% CI = -6.1, -3.9, P < 0.001) after receiving Qigong and the music therapy. Conclusion: Traditional Baduanjin Qigong and five-elements music therapy help to relieve anxiety and depression, and improve the sleep quality in patients with COVID-19 infection. Trial registration: Chinese Clinical Trial Registry ChiCTR2200059800.

Transfer of Se from sediments to the western mosquitofish Gambusia affinis: Tissue distribution, accumulation, and effects on the antioxidant physiology.

Selenium (Se) has been shown to cause various toxicities in predatory species (i.e., fish and birds) in Se-contaminated aquatic environments. However, trophic transfer of Se from abiotic environments to freshwater fish has been relatively less addressed. In this study, 2-month-old mosquitofish (Gambusia affinis) were fed Se-enriched oligochaete (Lumbriculus variegatus, exposed to different concentrations of Se(IV) at 0.0, 3.0, 10.0, and 30.0 µg/g dry weight for 7 days) for 45 days. Tissue distribution, Se speciation, and effects on the antioxidant physiology in G. affinis were assessed. The results showed Se was rapidly accumulated in the oligochaete, with 6.30 ± 1.20, 16.20 ± 2.10, and 34.50 ± 2.40 µg/g dw of total Se levels in the worms exposed to 3.0, 10.0, and 30.0 µg/g of Se(IV), respectively. Total Se levels were increased in a dose-dependent manner in fish tissues and Se(IV) from sediments was maternally transferred to the fish embryos. Se-Met-and Se-Cys-were the predominant Se species in the worm and fish tissues, accounting for a minimum of 91.01% of the total Se. Furthermore, increased lipid peroxidation and altered the activities of antioxidant enzymes and levels of GSH were noticed in G. affinis fed the Se-enriched L. variegatus. This study has demonstrated that Se(IV) is transferred from an abiotic vector to freshwater organisms, disturbing the antioxidant physiology in G. affinis and potentially their offspring. This study highlights the importance of dietary exposure on the accumulation and toxicity of Se in aquatic organisms.

Xanthatin suppresses pancreatic cancer cell growth via the ROS/RBL1 signaling pathway: In vitro and in vivo insights.

BACKGROUND: As a malignant digestive system tumor, pancreatic cancer has a high mortality rate. Xanthatin is a sesquiterpene lactone monomer compound purified from the traditional Chinese herb Xanthium strumarium L. It has been reported that Xanthatin exhibits inhibitory effects on various cancer cells in retinoblastoma, glioma, hepatoma, colon cancer, lung cancer, as well as breast cancer. However, in pancreatic cancer cells, only one report exists on the suppression of Prostaglandin E2 synthesis and the induction of caspase 3/7 activation in Xanthatin-treated MIA PaCa-2 cells, while systematic in vitro and in vivo investigations and related mechanisms have yet to be explored. PURPOSE: This research aims to explore the in vitro and in vivo effects of Xanthatin on pancreatic cancer and its molecular mechanisms. METHODS: The anticancer effects and mechanisms of Xanthatin on pancreatic cancer cells were assessed through employing cell counting kit-8 (CCK-8) assay, lactate dehydrogenase (LDH) assay, carboxyfluorescein diacetate succinimidyl ester (CFDA SE) cell proliferation assay, colony formation assay, wound healing assay, transwell assay, Annexin V-FITC/propidium iodide (PI) dual staining, Hoechst nuclear staining, Western blot analysis, phosphoproteomics, and reactive oxygen species (ROS) measurement. The in vivo anticancer effects of Xanthatin on pancreatic cancer cells were studied using a nude mouse model. RESULTS: The present study showed that Xanthatin can prevent the proliferation and metastasis of pancreatic cancer cells and trigger the exposure of phosphatidylserine (PS), chromatin condensation, and caspase activation, thereby inducing apoptosis. Phosphoproteomic analysis indicated that Xanthatin inhibits the phosphorylation of the proliferation-associated protein RBL1, and oxidative stress can lead to RBL1 dephosphorylation. Further investigation revealed that Xanthatin significantly upregulates ROS levels in pancreatic cancer cells, and the antioxidant N-acetylcysteine (NAC) can reverse Xanthatin-induced cell proliferation inhibition and apoptosis. In addition, Xanthatin can suppress pancreatic cancer cell growth in a xenograft nude mouse model with low toxicity to the mice. CONCLUSION: Xanthatin may inhibit the proliferation of pancreatic cancer cells and trigger apoptosis through the ROS/RBL1 signaling pathway.

Pharmacological effects and mechanisms of paeonol on antitumor and prevention of side effects of cancer therapy.

Cancer represents one of the leading causes of mortality worldwide. Conventional clinical treatments include radiation therapy, chemotherapy, immunotherapy, and targeted therapy. However, these treatments have inherent limitations, such as multidrug resistance and the induction of short- and long-term multiple organ damage, ultimately leading to a significant decrease in cancer survivors' quality of life and life expectancy. Paeonol, a nature active compound derived from the root bark of the medicinal plant Paeonia suffruticosa, exhibits various pharmacological activities. Extensive research has demonstrated that paeonol exhibits substantial anticancer effects in various cancer, both in vitro and in vivo. Its underlying mechanisms involve the induction of apoptosis, the inhibition of cell proliferation, invasion and migration, angiogenesis, cell cycle arrest, autophagy, regulating tumor immunity and enhanced radiosensitivity, as well as the modulation of multiple signaling pathways, such as the PI3K/AKT and NF-κB signaling pathways. Additionally, paeonol can prevent adverse effects on the heart, liver, and kidneys induced by anticancer therapy. Despite numerous studies exploring paeonol's therapeutic potential in cancer, no specific reviews have been conducted. Therefore, this review provides a systematic summary and analysis of paeonol's anticancer effects, prevention of side effects, and the underlying mechanisms involved. This review aims to establish a theoretical basis for the adjunctive strategy of paeonol in cancer treatment, ultimately improving the survival rate and enhancing the quality of life for cancer patients.

Composition of Sphagnum palustre L. extracts using different extraction methods.

Sphagnum palustre L. is a Chinese herbal medicine with a long history, however, few studies have been performed on its chemical composition and active effects. In this study, we investigated the composition and antibacterial and antioxidant capacities of extracts obtained from Sphagnum palustre L. phytosomes extracted with conventional solvents (water, methanol, and ethanol) and two different hydrogen bond donors (citric acid and 1,2-propanediol) modified with choline chloride-type deep eutectic solvents (DESs). The results show that Sphagnum palustre extracts contained 253 compounds, including citric acid, ethyl maltol, and thymol. The highest total phenolic content (TPC) was obtained with a DES extraction method combining 1,2-propanediol and choline chloride (39.02 ± 7.08 mg gallic acid equivalent/g dried weight (DW). This shows the composition of Sphagnum palustre as a natural product and the application of DESs in the extraction of active ingredients, demonstrating the potential of peat moss extracts in cosmetics and health products.

Clinical Characteristics of Human Papillomavirus Infection in the Male Genital Tract.

Objective: This study aims to understand the clinical characteristics of male HPV infection and provide data and information for the prevention and health of the male and female reproductive tracts in the region. Methods: A total of 390 male patients who underwent HPV examinations in outpatient clinics and physical examinations in 363 hospitals from December 2017 to May 2022 were selected. Samples were collected, and HPV genotyping was performed using multiplex fluorescent PCR. The HPV infection rate, genotype distribution, age distribution, and clinical symptom distribution were analyzed. Results: Out of 3,816 samples, the total HPV infection rate was 47.44% (185/390). The HPV infection rate in the symptomatic group was 57.09% (141/247), significantly higher than that in the asymptomatic group (P < .01). Among the subtypes, HPV6 accounted for the highest proportion (31.03%, 90/290), followed by HPV11 (14.14%, 41/290) and HPV52 (8.62%, 25/290). Types 6 and 11 were mainly concentrated in the symptomatic group (91.11%, 85.37%). The highest positive rate was observed in the 17-30-year-old group (45.41%, 85/185), followed by the 31-40-year-old group (28.11%, 52/185). The proportion of HPV infections with clinical symptoms of abnormal growth was 84.40% (119/141). HPV6 or/and HPV11 infections were mainly concentrated in the abnormal growth group, accounting for 90.76% (108/113). Conclusions: The rates of male HPV infection are high, particularly among individuals aged 17-40. Low-risk infections (types 6 and 11) cause male reproductive tract symptoms, including abnormal growth. High-risk infection (HPV52) correlates with local women's HPV subtype distribution and potential transmission. Therefore, screening for male HPV infection is crucial in preventing cervical cancer. Authorities should promote the development and early use of male HPV vaccines.