Effectiveness and safety of tetracyclines and quinolones in people with Mycoplasma pneumonia: a systematic review and network meta-analysis.

Background: The escalating resistance of Mycoplasma pneumoniae to macrolides has become a significant global health concern, particularly in low-income and middle-income countries (LMICs). Although tetracyclines and quinolones have been proposed as alternative therapeutic options, concerns regarding age-specific safety issues and the lack of consensus in recommendations across various national guidelines prevail. Thus, the primary objective of this study is to ascertain the most efficacious interventions for second-line treatment of M. pneumoniae infection while considering the age-specific safety issues associated with these interventions. Methods: In this systematic review and network meta-analysis we searched PubMed, Embase, CNKI, and WanFang Data, from inception up to November 11th, 2023. Studies of quinolones or tetracyclines for the treatment of people with M. pneumoniae infection were collected and screened by reading published reports, with any type of study included, and no individual patient-level data requested. A systematic review and direct meta-analysis compared the efficacy of tetracyclines and quinolones regarding time to defervescence (TTD) and the rates of fever disappearance within 24 h and 48 h of antibiotic administration, for managing M. pneumoniae infection. Bayesian network meta-analysis (NMA) was employed to indirectly assess the relative effectiveness of different interventions in people with M. pneumoniae infection and the safety profile of medication in paediatric patients. This study is registered with PROSPERO, CRD42023478383. Findings: The systematic review and direct meta-analysis included a total of 4 articles involving 246 patients, while the NMA encompassed 85 articles involving a substantial cohort of 7095 patients. The NMA measured the effectiveness across all ages and included 7043 patients, with a mean age of 37.80 ± 3.91 years. Of the 85 included studies, 14 (16.5%) were at low risk of bias, 71 (83.5%) were at moderate risk, and no studies were rated as having a high risk of bias. In the direct meta-analysis, no statistically significant differences were found between tetracyclines and quinolones concerning TTD (mean difference: -0.40, 95% CI: -1.43 to 0.63; I2 = 0%), fever disappearance rate within 24 h of antibiotic administration (OR: 0.37, 95% CI: 0.08-1.79; I2 = 58%), and fever disappearance rate within 48 h of antibiotic administration (OR: 1.10, 95% CI: 0.30-3.98; I2 = 59%). However, the comprehensive NMA analysis of clinical response (in 70 studies; n = 6143 patients), shortening of TTD (in 52 studies; n = 4363 patients), shortening length of cough relief or disappearance (in 39 studies; n = 3235 patients), fever disappearance rate at 48 h (in four studies; n = 418 patients) revealed that minocycline exhibited the most favourable outcomes across these various parameters, and the analysis of fever disappearance rate at 24 h (in three studies; n = 145 patients) revealed that levofloxacin may be the most effective, as indicated by the rank probabilities and surface under the cumulative ranking area (SUCRA) value. Moxifloxacin ranked second in clinical response and in shortening the length of cough relief or disappearance, and third in shortening TTD. Notably, when evaluating the occurrence of adverse reactions in paediatric patients (in four studies; n = 239 children), levofloxacin was associated with the highest SUCRA value rankings for the rate of adverse events. Interpretation: Our findings suggest that tetracyclines and quinolones may be equally effective. Based on the age of participants in the included studies, minocycline may be the most effective intervention for children over eight years of age when all preventive measures are considered, whereas moxifloxacin may benefit people under eight years of age. However, these results should be interpreted with caution, given the limited number of studies and patients included, and the heterogeneity between included studies. Based on a limited number of studies in children, levofloxacin is likely to have one of the highest rates of adverse reactions. The majority of the studies included in the NMA were from the Asian region, and more randomised controlled trials comparing different therapeutic strategies in patients with M. pneumoniae are warranted. This comparative study provides clinical pharmacists and clinicians with important information to enable them to make informed decisions about treatment options, considering drug efficacy and safety. Funding: The Natural Science Foundation of Fujian Province, China.

Effectiveness of novel ß-lactams for Pseudomonas aeruginosa infection: A systematic review and meta-analysis.

BACKGROUND: Novel ß-lactams have in vitro activity against Pseudomonas aeruginosa (PA), but their clinical performances and the selection criteria for practical use are still not clear. We aimed to evaluate the efficacy of novel ß-lactams for PA infection in various sites and to compare the efficacy of each agent. METHODS: We searched PubMed, Embase, Cochrane Library, and Web of Science for randomized controlled trials that used novel ß-lactams to treat PA infection. The primary outcomes were clinical cure and favorable microbiological response. Subgroup analyses were performed based on drug type, drug resistance of pathogens, and site of infection. Network meta-analysis was carried out within a Bayesian framework. RESULTS: In all studies combined (16 randomized controlled trials), novel ß-lactams indicated comparable performance to other treatment regimens in both outcome measures (relative risk = 1.04; 95% confidence interval 0.94-1.15; P = .43) (relative risk = 0.97; 95% confidence interval 0.81-1.17; P = .76). Subgroup analyses showed that the efficacy of ceftolozane-tazobactam (TOL-TAZ), ceftazidime-avibactam (CAZ-AVI), imipenem-cilastatin-relebactam, and cefiderocol had no apparent differences compared to control groups among different infection sites, drug types and drug resistance of PA. In network meta-analysis, the results showed no statistically significant differences between TOL-TAZ, CAZ-AVI, and cefiderocol. CONCLUSIONS: TOL-TAZ, CAZ-AVI, imipenem-cilastatin-relebactam, and cefiderocol are not inferior to other agents in the treatment of PA infection. Their efficacy is also comparable between TOL-TAZ, CAZ-AVI, and cefiderocol.

New light on ω-3 polyunsaturated fatty acids and diabetes debate: a population pharmacokinetic-pharmacodynamic modelling and intake threshold study.

OBJECTIVE: ω-3 polyunsaturated fatty acids (PUFA) are a key modifiable factor in the intervention of type 2 diabetes, yet recommendations for dietary consumption of ω-3 PUFA in type 2 diabetes remain ambiguous and controversial. Here, we revisit the subject in the light of population pharmacokinetic-pharmacodynamic (PPK-PD) modeling and propose a threshold for intake. RESEARCH DESIGN AND METHODS: Plasma levels of ω-3 PUFA and glycosylated hemoglobin (HbA1c) were measured as pharmacokinetic and pharmacodynamic indicator, respectively. The nonlinear mixed effect analysis was used to construct a PPK-PD model for ω-3 PUFA and to quantify the effects of FADS gene polymorphism, age, liver and kidney function, and other covariables. RESULTS: Data from 161 patients with type 2 diabetes in the community were modeled in a two-compartment model with primary elimination, and HDL was a statistically significant covariate. The simulation results showed that HbA1c showed a dose-dependent decrease of ω-3 PUFA plasma level. A daily intake of ω-3 PUFA at 0.4 g was sufficient to achieve an HbA1c level of 7% in more than 95% of patients. CONCLUSIONS: PPK/PD modeling was proposed as a multilevel analytical framework to quantitatively investigate finer aspects of the complex relationship between ω-3 PUFA and type 2 diabetes on genetic and non-genetic influence factors. The results support a beneficial role for ω-3 PUFA in type 2 diabetes and suggested the intake threshold. This new approach may provide insights into the interaction of the two and an understanding of the context in which changes occur.

Correlation between the prognostic nutritional index and outcomes in older patients aged ≥ 60 years with chronic heart failure.

BACKGROUND: Nutritional status is related to clinical outcomes in patients with chronic heart failure (CHF). The prognostic nutritional index (PNI) is a simple tool to assess nutrition. AIM: To evaluate the association between the PNI score and clinical outcomes in patients (60 years and older) hospitalized due to an acute exacerbation of CHF. METHOD: This was a retrospective observational study. Patients hospitalized for acute CHF exacerbation between July 2015 and May 2020 were analyzed. Patients were followed until January 31, 2021. The primary end point was cardiovascular-related readmissions and all-cause mortality after hospital discharge. Secondary outcomes were factors associated with all-cause mortality. Patients were divided into normal nutrition (PNI > 38), moderate malnutrition (PNI = 35-38), and severe malnutrition (PNI < 35) groups. RESULTS: The study included 355 patients (mean age 78 ± 9 years). The median follow-up was 769 days. Compared to survivors (n = 214), patients who expired (n = 133) were (1) older; (2) had lower PNI scores, lymphocyte counts, hemoglobin, albumin, total cholesterol, and serum sodium level; but (3) had higher serum creatinine levels, log(N-terminal-pro-B-type natriuretic peptide), and cardiac troponin I (P < 0.05). Multivariate analyses revealed that PNI was independently associated with all-cause mortality. The hazard ratio (HR) for moderate malnutrition versus normal nutrition was 1.624 (95% confidence interval [CI] 1.011-2.609, P = 0.045), while HR for severe malnutrition versus normal nutrition was 1.892 (95%CI 1.119-3.198, P = 0.017). Malnourished patients had significantly higher rates of cardiovascular readmissions and all-cause mortality. CONCLUSION: Lower PNI (malnutrition) was associated with worse clinical outcomes and was independently associated with all-cause mortality in patients with CHF.

Transcriptome profiling of transcription factors in Ganoderma lucidum in response to methyl jasmonate.

Ganoderma lucidum is a traditional Chinese medicine and its major active ingredients are ganoderma triterpenoids (GTs). To screen for transcription factors (TFs) that involved in the biosynthetic pathway of GTs in G. lucidum, the chemical composition in mycelia, primordium and fruiting body were analyzed, and the transcriptomes of mycelia induced by methyl jasmonate (MeJA) were analyzed. In addition, the expression level data of MeJA-responsive TFs in mycelia, primordia and fruiting body were downloaded from the database, and the correlation analysis was carried out between their expression profiles and the content of total triterpenoids. The results showed that a total of 89 components were identified, and the content of total triterpenoids was the highest in primordium, followed by fruiting body and mycelia. There were 103 differentially expressed TFs that response to MeJA-induction including 95 upregulated and 8 downregulated genes. These TFs were classified into 22 families including C2H2 (15), TFII-related (12), HTH (9), fungal (8), bZIP (6), HMG (5), DADS (2), etc. Correlation analysis showed that the expression level of GL23559 (MADS), GL26472 (HTH), and GL31187 (HMG) showed a positive correlation with the GTs content, respectively. While the expression level of GL25628 (fungal) and GL26980 (PHD) showed a negative correlation with the GTs content, respectively. Furthermore, the over expression of the Glmhr1 gene (GL25628) in Pichia pastoris GS115 indicated that it might be a negative regulator of GT biosynthesis through decreasing the production of lanosterol. This study provided useful information for a better understanding of the regulation of TFs involved in GT biosynthesis and fungal growth in G. lucidum.

Clinical validation of the two-point method for predicting vancomycin AUC based on peak and trough plasma concentrations.

BACKGROUND: Vancomycin area under the curve/minimum inhibitory concentration (AUC/MIC) has been proposed as a therapeutic drug monitoring (TDM) target to dose vancomycin. It is time-consuming to estimate AUCs using traditional methods. A two-point trough-peak method is more straightforward for calculating the vancomycin AUC. However, the technique and the AUC/MIC target have not been validated in Chinese patients. AIM: To compare the clinical outcomes of vancomycin therapy in Chinese older adults (aged > 60 years) between the trough-only and the two-point peak-trough AUC TDM approaches. METHOD: The patients were divided into study and control groups according to TDM approaches. A trough-based TDM was used in the control group (target trough level 15-20 mg/L). Stanford University has provided a method to predict vancomycin AUC using peak-valley concentration alone (two-point method). A two-point trough-peak TDM approach was employed in the study group (target AUC/MIC ≥ 400). The effect of vancomycin was evaluated in terms of clinical findings, laboratory values, and bacteriologic responses. The effects of treatment and kidney functions were compared between the two groups. RESULTS: A total of 389 patients met the study inclusion criteria, and 189 were excluded based on the exclusion criteria. Of the 200 patients, 80 received the two-point TDM approach (the study group), and 120 were monitored using the trough-based approach (the control group). The average age was 69.8 ± 7.1 years. Staphylococcus aureus (34%) was the most common Gram-positive bacteria. No vancomycin-related nephrotoxicity was observed in either group. The percentages of patients with an excellent response to vancomycin therapy were significantly higher in the study group than in the control group, 90% (72/80) versus 73.3% (88/120), P = 0.0039. CONCLUSION: The two-point peak-trough method is practical for obtaining vancomycin AUC. The AUC/MIC ≥ 400 target demonstrates treatment effectiveness and safety in older Chinese patients.

Higher Teicoplanin Blood Level Needed in Elderly Critically Ill Patients.

BACKGROUND: Significant changes in the pathophysiology of older critically ill patients may affect the pharmacokinetics and pharmacodynamics of teicoplanin. This study aimed to determine the optimal teicoplanin blood level in this patient population. METHODS: 128 older critically ill and 86 older non-critically ill patients were involved and analyzed. RESULTS: The target thresholds of teicoplanin blood concentrations in older critically ill patients and non-critically ill patients should be 31.4mg/L and 15.3mg/L, respectively. The dose of teicoplanin in older critically ill patients should be greater than 800 mg to achieve the target blood level. CONCLUSION: An individualized dosing approach of teicoplanin based on therapeutic drug monitoring is necessary for older critically ill patients.

Quadruple therapy for asymptomatic COVID-19 infection patients.

INTRODUCTION: The novel coronavirus (COVID-19) is currently in epidemic stage. After large-scale interpersonal infection, asymptomatic patients appear. Whether asymptomatic patients are contagious or not and whether they need medication are the arguments among clinical experts. AREAS COVERED: This paper reports a special asymptomatic couple with COVID-19, of which the male patient is an intercity bus driver but has not induced confirmed infection of his 188 passengers. The patients were treated with four combinations of lopinavir/ritonavir tablets, arbidol tablets, Lianhuaqingwen granules, and recombinant human interferon-α2b (IFN-α2b) injection via aerosol. Their clinical characteristics and medication were summarized and analyzed. EXPERT OPINION: The two asymptomatic patients far away from Wuhan did not seem to be highly contagious. They improved obviously, after treatment with the quadruple therapy, but the effective drug is still unknown. It should be noted that lopinavir/ritonavir tablets have many drug interactions and are the most likely drugs to cause hyperlipidemia and hyperglycemia in these two patients. IFN-α2b is more effective in the early stage of virus infection. Arbidol instruction dose may not be sufficient to inhibit the novel coronavirus in vivo. The evidence-based medicine of Lianhuaqingwen granules for treating various viral infections is just based on Chinese patients.

Biosynthesized of reduced graphene oxide nanosheets and its loading with paclitaxel for their anti cancer effect for treatment of lung cancer.

Multifunctional nanocarriers are in immediate need to develop anticancer activity for the treatment of cancers. In the present research, the graphene oxide was reduced via an efficient method which reduced to RGO by using Euphorbia milii leaves extract. Thus obtained RGO nanocomposites were subsequently characterized by means UV-Vis absorption technique. AFM imaging was further performed in order to analyze the surface morphology of GO nanosheet as well as to estimate the average thickness of the GO nanosheets before and after the addition of Euphorbia milii leaves extract. Furthermore, the anticancer effect of RGO-loaded PTX (RGO/PTX) on A549 (Human lung cancer cell lines) was evaluated by MTT assay. The results displayed that with the increase in the concentration of RGO/PTX to200 ??g/mL, the cell viability reduced to 29%. Even more increase in the concentration to 500 ??g/mL of RGO/PTX, the cell viability also showed rapid reduction to 10%. Based on this, we can conclude that the increased concentration of RGO/PTX decreased the cell viability of A549 cell lines tremendously and has the potential to serve in the lung carcinoma targeted chemotherapy.

Targeting Thioredoxin System with an Organosulfur Compound, Diallyl Trisulfide (DATS), Attenuates Progression and Metastasis of Triple-Negative Breast Cancer (TNBC).

BACKGROUND/AIMS: Metastasis is the leading cause resulting in high mortality in triple negative breast cancer (TNBC) patients. Cancer cells are skilled at utilizing thioredoxin (Trx) system as an efficient antioxidant system to counteract oxidative damage, facilitating the occurrence of metastasis. Here, we identified an organosulfur compound named DATS isolated from garlic, that inhibits the expression of Trx-1 and the enzyme activity of Trx reductase in breast cancer cells. METHODS: Tissue microarray of breast cancer patients and immunohistochemical method were used to analyze the role of Trx-1 in breast cancer metastasis. Spotaneous metastasis model and experimental metastasis model combined with HE staining, immunohistochemistry were used to verify in vivo anti-metastatic effect of DATS as well as its regulation on thioredoxin. Western blot, immunofluorescence, redox state assessment and detection of enzyme activity were employed to determine the effect of DATS on thioredoxin system. Trx-1 siRNA interference was used to investigate the conclusive evidence that Trx-1 was the target of DATS. RESULTS: In agreement with reduced Trx-1 nuclear translocation from cytoplasm by DATS, the production of reduced form of Trx-1 was dramatically decreased. Furthermore, in vivo, DATS administration was observed to significantly suppress spontaneous and experimental metastasis in nude mice. Delivery of DATS also resulted in decreased expression of Trx-1 as the direct target, as well as expression of NF-κB and MMP2/9 in primary tumor and lung tissue. Notably, the effects of DATS on the expression of downstream metastasis-associated genes were mediated by Trx-1, as demonstrated by the combination use of DATS and Trx-1 siRNA. CONCLUSION: Collectively, this present study indicates that targeting Trx system with DATS may provide a promising strategy for treating metastasis of TNBC.

Impact of CYP2A6 gene polymorphism on the pharmacokinetics of dexmedetomidine for premedication.

BACKGROUND: Dexmedetomidine is a widely used sedative in clinic, which is mainly metabolized by cytochrome P450 2A6 (CYP2A6). Dexmedetomidine was rarely reported for off-label usage of premedication, but lacking relevant pharmacokinetic investigations. Therefore, our study determined the dexmedetomidine pharmacokinetics of CYP2A6*4 allele in Chinese patients pretreated with dexmedetomidine whose mutation frequency of CYP2A6*4 are high, in order to provide clinical references. METHODS: Thirty-one elective surgery patients received premedication with 0.5 µg/kg dexmedetomidine via intravenous pump. Their plasma concentrations at multiple time-points and polymorphism of CYP2A6*4 were determined and statistically analyzed. RESULTS: 9 patients were *1/*4 or *4/*4, and 22 patients were *1/*1. The main pharmacokinetic parameters were area under curve (AUC) 1396.19 ± 332.47h· ng· l-1, peak blood concentration (Cmax) 495.50 ± 104.90ng· l-1, distribution volume (V) 0.68 ± 0.20 L/kg, clearance (CL) 0.38 ± 0.11 L/h/kg, distribution half-life (t1/2α) 0.05 ± 0.01h, elimination half-life (t1/2ß) 2.53 ± 0.04h. No significant pharmacokinetic differences were found among CYP2A6*1/*1, *1/*4, and *4/*4 patients. CONCLUSIONS: In Chinese patients pretreated with dexmedetomidine, T1/2ß was consistent with that published, but T1/2α, V and Cl were lower. It was unnecessary to consider the mutation when developing the precision regimen of dexmedetomidine.

Extracellular Vesicles: A New Perspective in Tumor Therapy.

In recent years, the study of extracellular vesicles has been booming across various industries. Extracellular vesicles are considered one of the most important physiological endogenous carriers for the specific delivery of molecular information (nucleonic acid, cytokines, enzymes, etc.) between cells. It has been discovered that they perform a critical role in promoting tumor cell growth, proliferation, tumor cell invasion, and metastatic ability and regulating the tumor microenvironment to promote tumor cell communication and metastasis. In this review, we will discuss (1) the mechanism of extracellular vesicles generation, (2) their role in tumorigenesis and cancer progression (cell growth and proliferation, tumor microenvironment, epithelial-mesenchymal transition (EMT), invasion, and metastasis), (3) the role of extracellular vesicles in immune therapy, (4) extracellular vesicles targeting in tumor therapy, and (5) the role of extracellular vesicles as biomarkers. It is our hope that better knowledge and understanding of the extracellular vesicles will offer a wider range of effective therapeutic targets for experimental tumor research.

Molecular Cancer Imaging in the Second Near-Infrared Window Using a Renal-Excreted NIR-II Fluorophore-Peptide Probe.

In vivo molecular imaging of tumors targeting a specific cancer cell marker is a promising strategy for cancer diagnosis and imaging guided surgery and therapy. While targeted imaging often relies on antibody-modified probes, peptides can afford targeting probes with small sizes, high penetrating ability, and rapid excretion. Recently, in vivo fluorescence imaging in the second near-infrared window (NIR-II, 1000-1700 nm) shows promise in reaching sub-centimeter depth with microscale resolution. Here, a novel peptide (named CP) conjugated NIR-II fluorescent probe is reported for molecular tumor imaging targeting a tumor stem cell biomarker CD133. The click chemistry derived peptide-dye (CP-IRT dye) probe afforded efficient in vivo tumor targeting in mice with a high tumor-to-normal tissue signal ratio (T/NT > 8). Importantly, the CP-IRT probes are rapidly renal excreted (≈87% excretion within 6 h), in stark contrast to accumulation in the liver for typical antibody-dye probes. Further, with NIR-II emitting CP-IRT probes, urethra of mice can be imaged fluorescently for the first time noninvasively through intact tissue. The NIR-II fluorescent, CD133 targeting imaging probes are potentially useful for human use in the clinic for cancer diagnosis and therapy.

Pharmacokinetics of multiple doses of teicoplanin in Chinese elderly critical patients.

BACKGROUND: The dose-effect relationship of teicoplanin has been a hot topic of clinical concern, but there was lack of the evidence of Chinese patients to optimize dosage, especially in elderly critical patients, whose plasma protein, liver and kidney function are greatly different from ordinary patients. METHODS: Elderly critical patients were divided into high-dose(800mg), medium-dose (600mg) and low-dose (400mg) groups, which consisted of 6 cases of each group. Three groups were taken intravenous blood at different times after the last administration of teicoplanin to measure teicoplanin plasma concentration. RESULTS: The t1/2 of high-dose, middle-dose and low-dose groups were 70.76 ± 11.72h, 73.60 ± 9.48h, 80.24 ± 6.75h, respectively; CL were 0.14 ± 0.09mL ∙ h-1 ∙ kg-1, 0.11 ± 0,05mL ∙ h-1 ∙ kg-1, 0.12 ± 0.06mL ∙ h-1 ∙ kg-1 respectively. The Cmax and AUC0-t of the three dose groups were linearly correlated with the dose. CONCLUSIONS: In Chinese elderly critical patients, t1/2 of teicoplanin was consistent with that of literatures published, however, CL were higher. The pharmacokinetics of teicoplanin at the range of 400 ~ 800mg is linear pharmacokinetics, indicating that the dosage regimens for patients were more simply and accurately adjusted according to therapeutic drug monitoring.

SLCO1B1 rs4149056 genetic polymorphism predicting methotrexate toxicity in Chinese patients with non-Hodgkin lymphoma.

AIM: To investigate the impact of polymorphisms in the FPGS, GGH and SLCO1B1 genes on high dose methotrexate (HD-MTX) related toxicity in Chinese patients with non-Hodgkin lymphoma (NHL). MATERIALS & METHODS: We analyzed FPGS (rs10106), GGH (rs719235, rs10464903, rs12681874), SLCO1B1 (rs4149056) genetic polymorphisms in 105 Chinese patients with NHL treated with HD-MTX. RESULTS: There was a statistically significant impact of the SLCO1B1 rs4149056 polymorphism on hepatotoxicity. Patients with TC and CC genotype had more hepatotoxicity than TT genotype (60 vs 32.94%, p = 0.025). After adjusting for disease stage, dosage, infusion time and therapy method, SLCO1B1 rs4149056 genotype remained significantly associated with hepatotoxicity (p = 0.028). CONCLUSION: SLCO1B1 rs4149056 genetic variants can affect the HD-MTX-related toxicity in Chinese patients with NHL.

Epithelial-mesenchymal transition: potential regulator of ABC transporters in tumor progression.

Epithelial-mesenchymal transition (EMT) can directly contribute to some malignant phenotypes of tumor cells including invasion, metastasis and resistance to chemotherapy. Although EMT is widely demonstrated to play a critical role in chemoresistance and metastasis, the potential signaling network between EMT and drug resistance is still unclear. The distribution of drugs in the internal and external environment of the tumor cells is tightly linked with ATP-binding cassette (ABC) transporters. Recent studies have shown that ABC transporters expression changed continuously during EMT. We believe that EMT is an important regulator of ABC transporters. In this review, we discuss how EMT regulates ABC transporters and their potential linkages. And we hope the knowledge of EMT and ABC transporters will offer more effective targets to experimental research.

Pleiotropic effects of herbs characterized with blood-activating and stasis-resolving functions on angiogenesis.

Accumulative evidences have underpinned the nature candidates from Chinese medicine (CM), particularly CM served as blood activating and stasis resolving (BASR, Huoxue Huayu in Chinese) by targeting tumor-associated angiogenesis. However, recent experiment research on the therapeutic angiogenesis by BASR-CM attracts wide attention and discussion. This opinion review focused on the underlying link between two indications and anticipated that (1) BASR-CM might emphasize on a balanced multi-cytokines network interaction; (2) BASR-CM might address on the nature of diseases prior to differently affecting physiological and pathological angiogenesis; (3) BASR-CM might mainly act on perivascular cells, either promotes arteriogenesis by increasing arteriogenic factors in ischemic diseases, or simultaneously keep a quiescent vasculature to impede angiogenesis in tumor context.

Up-Regulation of CYP2C19 Expression by BuChang NaoXinTong via PXR Activation in HepG2 Cells.

BACKGROUND: Cytochrome P450 2C19 (CYP2C19) is an important drug-metabolizing enzyme (DME), which is responsible for the biotransformation of several kinds of drugs such as proton pump inhibitors, platelet aggregation inhibitors and antidepressants. Previous studies showed that Buchang NaoXinTong capsules (NXT) increased the CYP2C19 metabolic activity in vitro and enhanced the antiplatelet effect of clopidogrel in vivo. However, the underlying molecular mechanism remained unclear. In the present study, we examined whether Pregnane X receptor (PXR) plays a role in NXT-mediated regulation of CYP2C19 expression. METHODS: We applied luciferase assays, real-time quantitative PCR (qPCR), Western blotting and cell-based analysis of metabolic activity experiments to investigate the NXT regulatory effects on the CYP2C19 promoter activity, the mRNA/ protein expression and the metabolic activity. RESULTS: Our results demonstrated that NXT significantly increased the CYP2C19 promoter activity when co-transfected with PXR in HepG2 cells. Mutations in PXR responsive element abolished the NXT inductive effects on the CYP2C19 promoter transcription. Additionally, NXT incubation (150 and 250µg/mL) also markedly up-regulated endogenous CYP2C19 mRNA and protein levels in PXR-transfected HepG2 cells. Correspondingly, NXT leaded to a significant enhancement of the CYP2C19 catalytic activity in PXR-transfected HepG2 cells. CONCLUSION: In summary, this is the first study to suggest that NXT could induce CYP2C19 expression via PXR activation.

Antimetastatic Therapies of the Polysulfide Diallyl Trisulfide against Triple-Negative Breast Cancer (TNBC) via Suppressing MMP2/9 by Blocking NF-κB and ERK/MAPK Signaling Pathways.

BACKGROUND: Migration and invasion are two crucial steps of tumor metastasis. Blockage of these steps may be an effective strategy to reduce the risk. The objective of the present study was to investigate the effects of diallyl trisulfide (DATS), a natural organosulfuric compound with most sulfur atoms found in garlic, on migration and invasion in triple negative breast cancer (TNBC) cells. Molecular mechanisms underlying the anticancer effects of DATS were further investigated. METHODS AND RESULTS: MDA-MB-231 cells and HS 578t breast cancer cells were treated with different concentrations of DATS. DATS obviously suppressed the migration and invasion of two cell lines and changed the morphological. Moreover, DATS inhibited the mRNA/protein/ enzymes activities of MMP2/9 via attenuating the NF-κB pathway. DATS also inhibited ERK/MAPK rather than p38 and JNK. CONCLUSION: DATS inhibits MMP2/9 activity and the metastasis of TNBC cells, and emerges as a potential anti-cancer agent. The inhibitory effects are associated with down-regulation of the transcriptional activities of NF-κB and ERK/MAPK signaling pathways.

Effect of aqueous extracts of several kinds of herbs on human platelet aggregation and expression of P-selectin in vitro.

OBJECTIVE: To study the effect of aqueous extract of several kinds of herbs on human platelet aggregation and expression of P-selectin in vitro. METHODS: Blood was collected from volunteers. Effects of the prepared water extracts of herbs on platelet aggregation were monitored on a Packs-4 aggregometer. The fluorescence intensity of water extracts of Caulis Spatholobi, Flos Carthami and Rhizoma Curcumae on the expression of P-selectin in human platelets of healthy persons was measured with flow cytometry. RESULTS: Out of several herbs investigated, Flos Carthami and Rhizoma Curcumae potently inhibited platelet aggregation after incubation with platelet-rich plasma (PRP) for 15 min. Caulis Spatholobi Flos Carthami and Rhizoma Curcumae inhibited adenosine-5'-diphosphate (ADP) or platelet activating factor (PAF)-induced platelet aggregation in PRP in a dose-dependent manner. In contrast to Flos Carthami and Rhizoma Curcumae, Caulis Spatholobi could not inhibit thrombin-induced platelet aggregation. Despite its inability to inhibit thrombin-induced platelet aggregation in PRP, Caulis Spatholobi had a greater anti-aggregating activity in PRP induced by ADP or PAF. Caulis Spatholobi and Flos Carthami showed significant inhibitory effects on the expression of P-selectin. CONCLUSIONS: Caulis Spatholobi, Flos Carthami and Rhizoma Curcumae have potent anti-platelet properties, and their inhibitory actions are mediated via different mechanisms. Caulis Spatholobi inhibited ADP-induced platelet aggregation but not by thrombin, indicating that its mechanism of action might be independent of the thromboxane pathway. The effect of Caulis Spatholobi and Flos Carthami were associated with suppressing the expression of P-selectin.