Investigation of the efficacy of Dengzhan Shengmai capsule against heart failure with preserved ejection fraction.

ETHNOPHARMACOLOGICAL RELEVANCE: Heart failure with preserved ejection fraction (HFpEF) has emerged as a condition with high incidence and mortality rates in recent years. Dengzhan Shengmai capsule (DZSMC) is a Chinese patent medicine based on the classic recipe "Shengmai powder". The relevant Chinese medicine ratio of Erigeron breviscapus (Vaniot) Hand.-Mazz., Panax ginseng C.A.Mey., Schisandra chinensis (Turcz.) Baill., and Ophiopogon japonicus (Thunb.) Ker Gawl. is 30 : 6 : 6 : 11 . Traditional Chinese medicine (TCM) is being increasingly explored as a safe and effective treatment modality for HFpEF. Clinical studies have shown that DZSMCs can effectively treat heart failure, however, the mechanism of action of DZSMCs in the treatment of HFpEF are still not clear. AIM OF THE STUDY: To investigate the efficacy and underlying mechanisms of Dengzhan Shengmai capsule (DZSMC), in the treatment of HFpEF by focusing on its ability to treat microvascular inflammation. MATERIALS AND METHODS: First, the efficacy of DZSMCs against HFpEF was predicted by network pharmacology. After 3 days of adaptive feeding in SPF-grade polypropylene cages, the mice in the Model group, DZSMC group, and Captopli group underwent single kidney resection, and micropumps were implanted in their backs for continuous infusion of aldosterone at a rate of 0.3 µg/h for 4 weeks. Moreover, the mice were given DZSMCs or Captopli via oral gavage for four weeks. Overall, cardiac function was evaluated in mice, and cardiac ultrasound and blood biochemical indices were evaluated in HFpEF mice. RESULTS: DZSMCs can ameliorate myocardial hypertrophy and cardiomyocyte damage caused by excessive myocardial stress, ultimately mitigating long-term cardiac impairment; it aids in the restoration of myocardial fibre proliferation and enhances mitochondrial morphology and function. In a murine model of ventricular hypertrophy and left ventricular dysfunction, which are indicative of cardiac insufficiency, the administration of DZSMCs resulted in notable improvements. Echocardiographic and overall assessments of cardiac function revealed a reduction in cardiac dysfunction and ventricular hypertrophy post-DZSMC intervention. Moreover, intervention with DZSMCs led to a reduction in the serum levels of several markers associated with chronic systemic inflammation, such as sST2, IL1RL1, CRP, and IL-6. Simultaneously, the levels of indicators of microvascular inflammation, including VCAM and E-SELECTIN, also decreased following DZSMC intervention. These findings suggest the potential multifaceted impact of DZSMCs in alleviating cardiac abnormalities, mitigating systemic inflammation, and reducing microvascular inflammatory markers, highlighting their promising therapeutic role in managing myocardial health. CONCLUSIONS: These results provide novel evidence that DZSMCs improve HFpEF by regulating microvascular inflammation.

Ni introduction induced non-radical degradation of bisphenol A in spinel ferrite/H2O2 systems.

Herein, we achieved reactive oxygen species manipulation using transition metal spinel ferrites (NixCo1-xFe2O4, x = 0, 0.5, 1) as Fenton-like agents. Specifically, NiFe2O4 mainly produced 1O2 and high-valence metals, while CoFe2O4 mainly produced ˙OH, from H2O2 activation. With bisphenol A as a model pollutant, the NiFe2O4/H2O2 system exhibited good resistance to ion interference.

Trimethylamine-N-oxide (TMAO) and predicted risk of cardiovascular events after partial nephrectomy.

INTRODUCTION: Emerging evidence suggests that uremic toxins, in particular trimethylamine-N-oxide(TMAO), indoxyl-sulfate(IS), and p-cresyl-sulfate(PCS), may associate with increased risk of cardiovascular events(CVe). However, whether uremic toxins increase after partial nephrectomy(PN) and their correlation with risk for CVe remains unknown. METHODS: 100 patients managed with PN were retrospectively reviewed. TMAO/IS/PCS levels were examined by liquid chromatography-mass-spectrometry. Renal-parenchymal-volume-preservation(RPVP) was estimated from CT scans. Predicted risks for CVe were obtained using the Framingham score. Linear regression assessed association between uremic toxins, GFR and risk of CVe. Logistic regression evaluated factors associated with post-PN TMAO. RESULTS: TMAO, IS and PCS increased from 1.7, 3.7 and 3.5 µmol/L before PN to 3.6, 5.4 and 7.4 µmol/L at latest follow-up, respectively, while GFR declined from 102 to 93 ml/min/1.73 m2 (all p<0.001). TMAO, IS and PCS levels all negatively correlated with GFR(all p<0.001). Predicted 10-year risk of CVe increased from 1.1% pre-PN to 1.7% post-PN(p<0.001), primarily due to increased age(p<0.001), blood pressure(p = 0.002) and total cholesterol(p = 0.003). TMAO(ß = 0.038) and GFR (ß = -0.02) were independent predictors for predicted 10-year CVe risk on multivariable-analysis. Increased TMAO was an early and sustained finding maintained through 5 years, unlike IS, PCS and eGFR. On multivariable analysis, increased pre-PN TMAO(OR = 2.79) and decreased RPVP(OR = 3.23) were identified as independent risk factors for higher post-PN TMAO, while ischemia type/duration failed to correlate. CONCLUSION: Uremic toxin levels increased after PN correlating with reduced GFR. Higher TMAO independently associated with greater predicted 10-year CVe risk. Parenchymal mass preserved rather than ischemia time or type associated with increased TMAO.

Imaging-based adipose biomarkers for predicting clinical outcomes of cancer patients treated with immune checkpoint inhibitors: a systematic review.

Background: Since the application of Immune checkpoint inhibitors (ICI), the clinical outcome for metastatic cancer has been greatly improved. Nevertheless, treatment response varies in patients, making it urgent to identify patients who will receive clinical benefits after ICI therapy. Adipose body composition has proved to be associated with tumor response. In this systematic review, we aimed to summarize the current evidence on imaging adipose biomarkers that predict clinical outcomes in patients treated with ICI in various cancer types. Methods: Embase and PubMed were searched from database inception to 1st February 2023. Articles included investigated the association between imaging-based adipose biomarkers and the clinical outcomes of patients treated with ICI. The methodological quality of included studies was evaluated through Newcastle- Ottawa Quality Assessment Scale and Radiomics Quality Score tools. Results: Totally, 22 studies including 2256 patients were selected. Non-small cell lung cancer (NSCLC) had the most articles (6 studies), followed by melanoma (5 studies), renal cell carcinoma (RCC) (3 studies), urothelial carcinoma (UC) (2 studies), head and neck squamous cell carcinoma (HNSCC) (1 study), gastric cancer (1 study) and liver cancer (1 study). The remaining 3 studies investigated metastatic solid tumors including various types of cancers. Adipose biomarkers can be summarized into 5 categories, including total fat, visceral fat, subcutaneous fat, intramuscular fat and others, which exerted diverse correlations with patients' prognosis after being treated with ICI in different cancers. Most biomarkers of body fat were positively associated with survival benefits. Nevertheless, more total fat was predictable of worse outcomes in NSCLC, while inter-muscular fat was associated with poor clinical benefits in UC. Conclusion: There is relatively well-supported evidence for imaging-based adipose biomarkers to predict the clinical outcome of ICI. In general, most of the studies show that adipose tissue is positively correlated with clinical outcomes. This review summarizes the significant biomarkers proven by researches for each cancer type. Further validation and large independent prospective cohorts are needed in the future. The protocol of this systematic review has been registered at the International Prospective Register of Systematic Reviews (http://www.crd.york.ac.uk/PROSPERO, registration no: CRD42023401986).

Targeting the Metabolic Enzyme PGAM2 Overcomes Enzalutamide Resistance in Castration-Resistant Prostate Cancer by Inhibiting BCL2 Signaling.

The next-generation androgen receptor (AR) inhibitor enzalutamide is the mainstay treatment for metastatic prostate cancer. Unfortunately, resistance occurs rapidly in most patients, and once resistance occurs, treatment options are limited. Therefore, there is an urgent need to identify effective targets to overcome enzalutamide resistance. Here, using a genome-wide CRISPR-Cas9 library screen, we found that targeting a glycolytic enzyme, phosphoglycerate mutase PGAM2, significantly enhanced the sensitivity of enzalutamide-resistant prostate cancer cells to enzalutamide both in vivo and in vitro. Inhibition of PGAM2 together with enzalutamide treatment triggered apoptosis by decreasing levels of the antiapoptotic protein BCL-xL and increasing activity of the proapoptotic protein BAD. Mechanistically, PGAM2 bound to 14-3-3ζ and promoted its interaction with phosphorylated BAD, resulting in activation of BCL-xL and subsequent resistance to enzalutamide-induced apoptosis. In addition, high PGAM2 expression, which is transcriptionally regulated by AR, was associated with shorter survival and rapid development of enzalutamide resistance in patients with prostate cancer. Together, these findings provide evidence of a nonmetabolic function of PGAM2 in promoting enzalutamide resistance and identify PGAM2 inhibition as a promising therapeutic strategy for enzalutamide-resistant prostate cancer. SIGNIFICANCE: PGAM2 promotes resistance to enzalutamide by activating antiapoptotic BCL-xL and suppressing apoptosis, indicating that PGAM2 is a potential target for overcoming enzalutamide resistance in prostate cancer.