Effect of inorganic nitrate supplementation on blood pressure in older adults: A systematic review and meta-analysis.

BACKGROUND: Previous clinical studies have shown controversial results regarding the effect of inorganic nitrate supplementation on blood pressure (BP) in older individuals. We performed this systematic review and meta-analysis to assess the effect of inorganic nitrate on BP in older adults. METHODS: Eligible studies were searched in Cochrane Library, PubMed, Scopus, Web of Science, and Embase. Randomized controlled trials which evaluated the effect of inorganic nitrate consumption on BP in older adults were recruited. The random-effect model was used to calculate the pooled effect sizes. RESULTS: 22 studies were included in this meta-analysis. Overall, inorganic nitrate consumption significantly reduced systolic blood pressure (SBP) by -3.90 mmHg (95% confidence interval: -5.23 to -2.57; P < 0.001) and diastolic blood pressure (DBP) by -2.62 mmHg (95% confidence interval: -3.86 to -1.37; P < 0.005) comparing with the control group. Subgroup analysis showed that the BP was significantly reduced when participants' age≥65, BMI>30, or baseline BP in prehypertension stage. And both SBP and DBP decreased significantly after acute nitrate supplementation of a single dose (<1 day) or more than 1-week. However, participants with hypertension at baseline were not associated with significant changes in both SBP and DBP. Subgroup analysis of measurement methods showed that only the resting BP group showed a significant reduction in SBP and DBP, compared with the 24-h ambulatory BP monitoring (ABPM) group and daily home BP measurement group. CONCLUSION: These results demonstrate that consuming inorganic nitrate can significantly reduce SBP and DBP in older adults, especially in whose age ≥ 65, BMI＞30, or baseline BP in prehypertension stage.

The Effect of Lactobacillus Consumption on Human Blood Pressure: a Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVES: Previous clinical studies have shown controversial results regarding the effect of Lactobacillus supplementation on blood pressure (BP). The purpose of this systematic review and meta-analysis is to examine the effect of Lactobacillus consumption on BP. METHODS: Eligible randomized controlled trials (RCTs) were searched from five electronic databases until May 2020. In total, 18 studies were included in our meta-analysis. Quality of the selected studies was assessed, and a random-effects model was used to calculate the overall effect sizes of weighted mean differences (WMD). This systematic review was registered in PROSPERO with the number: CRD42019139294. RESULTS: Lactobacillus consumption significantly reduced systolic blood pressure (SBP) by -2.74 mmHg (95% confidence interval, -4.96 to -0.51) and diastolic blood pressure (DBP) by -1.50 mmHg (95% confidence interval, -2.44 to -0.56) when comparing with the control group. Subgroup analysis showed that type 2 diabetes mellitus (T2DM) patients, Asian individuals, or borderline hypertension participants were more sensitive to daily consumption of Lactobacillus. And the effect of Lactobacillus on BP-reduction was more significant in capsule form, with the dose was above 5 × 109 colony-forming unit (CFU)/day or lasted for more than 8 weeks. CONCLUSIONS: Our present study suggests that Lactobacillus consumption in capsule form when the daily dose is above 5 × 109 CFU for more than 8 weeks can decrease SBP or DBP in T2DM patients, borderline hypertension participants or Asian individuals.

Extracts of Cordyceps sinensis inhibit breast cancer growth through promoting M1 macrophage polarization via NF-κB pathway activation.

ETHNOPHARMACOLOGICAL RELEVANCE: Cordyceps sinensis is a traditional Chinese medicine. It is widely reported that Cordyceps sinensis has inhibitory effect on tumor growth and immunoregulation effect on macrophages. However, the exact mechanism of Cordyceps sinensis on macrophage polarization in tumor progression is not known. AIM OF STUDY: We aimed to investigate the role of extracts of Cordyceps sinensis on macrophage polarization and its underlying mechanism in antitumor activity. MATERIALS AND METHODS: The 4T1 orthotopic xenograft mouse model and immunohistochemical staining were used to investigate the effect of Cordyceps sinensis on breast tumor and the change of the macrophages phenotype in the tumor, respectively. A 3D co-culture assay was used to confirm the activity in vitro. Measurement of cytokines and NO, quantitative real-time PCR and flow cytometry assays were used to investigate the effect of Cordyceps sinensis on the macrophage polarization in vitro. The mechanism of the effect of Cordyceps sinensis on macrophages was investigated by using western blot assays. RESULTS: In the orthotopic mouse tumor model, Cordyceps sinensis inhibited the 4T1 tumor growth in a dose dependent manner, and the immunohistochemical staining analysis showed that there is a positive correlation between tumor growth inhibition and macrophage M1-like polarized phenotype. The cytokines and NO measurement, quantitative real-time PCR assay and flow cytometry assays confirmed that Cordyceps sinensis could promote macrophage differentiation toward the M1 phenotype. The 3D co-culture assay and western blot assay showed that Cordyceps sinensis could inhibit tumor growth by promoting macrophage polarization and enhance its activity by activating the NF-κB signaling pathway. CONCLUSION: These findings suggest that Cordyceps sinensis could potently suppress TNBC progression by promoting M1 phenotypic differentiation of macrophages via activation NF-κB signaling pathway in tumor microenvironment.

Tumor Hypervascularity and hand-foot-skin reaction predict better outcomes in combination treatment of TACE and Sorafenib for intermediate hepatocellular carcinoma.

BACKGROUND: To validate the robust predictive values of tumor vascularity and hand-foot-skin reaction (HFSR) in combination treatment of transarterial chemoembolization (TACE) and sorafenib for patients with intermediate hepatocellular carcinoma (HCC), and then select the potential candidates who would survive best from such treatment. METHODS: A total of 132 treatment-naive patients with intermediate HCC undergoing combination therapy of TACE and sorafenib were recruited between January 2010 and December 2014. The tumor vascularity was defined according to digital subtraction angiography (DSA) and HFSR was assessed by the national cancer institute common terminology criteria for adverse events (NCI-CTCAE). The Mann-Whitney U test was used to assess the correlation between vascularity and radiologic response; time to radiologic progression (TTP) and overall survival (OS) were evaluated using Kaplan-Meier techniques and compared by log-rank test; factors associated with them were evaluated using multivariate Cox regression analysis. RESULTS: During a median follow up of 17.3 months, it was revealed that hypervascularity and development of ≥2 grade of HFSR within 60 days after sorafenib initiation were favorable predictors for TTP (HR 0.378, p < 0.001; HR 0.627, p = 0.018) and OS (HR 0.499, p = 0.002; HR 0.555, p = 0.004). The median TTP and OS for patients with both were 12.2 and 29.1 months, which were better than patients with either of them (6.0 months, HR 1.74, p = 0.012; 16.5 months, HR 1.73, p = 0.021), as well as those with neither (2.9 months, HR 3.74, p < 0.001; 11.9 months, HR 3.17, p < 0.001). CONCLUSIONS: Tumor hypervascularity and development of ≥2 grade of HFSR within 60 days were favorable predictive factors for the combination treatment of TACE and sorafenib, with both of which the patients survived longest and might be the potential candidates.

Hand-foot-skin reaction of grade ≥ 2 within sixty days as the optimal clinical marker best help predict survival in sorafenib therapy for HCC.

Background & Aims Sorafenib-related adverse events have been reported as clinical surrogates for treatment response in hepatocellular carcinoma (HCC); however, no consensus has been reached regarding the definition of responders. We evaluated the predictive abilities of different definitions for sorafenib response based on treatment-emergent adverse events, aiming to identify the most discriminatory one as a clinical marker. Methods From January 2010 to December 2014, 435 consecutive HCC patients treated with sorafenib were enrolled. Considering the type, severity and timing of adverse events, twelve different categories of sorafenib response were defined. By comparing their discriminatory abilities for survival, an indicative criterion was defined, the prognostic value of which was evaluated by time-dependent multivariate analysis, validated in various subsets and confirmed by landmark analysis. Results Using concordance (C)-index analysis and time-dependent receiver operating characteristic curves, the development of a hand-foot-skin reaction ≥ grade 2 within 60 days of sorafenib initiation (2HFSR60) showed the highest discriminating value. Based on this criterion, 161 (37.0%) sorafenib responders achieved decreased risk of death by 47% (adjusted HR 0.53, 95%CI 0.43-0.67, P < 0.001) and likelihood of progression by 26% (adjusted HR 0.74, 95%CI 0.58-0.96, P = 0.020) compared with non-responders. Notably, 2HFSR60 remained an effective discriminator among most subgroups and had superior predictive ability to previous definitions, even according to the landmark analysis. Conclusions Our study demonstrated that 2HFSR60, with the best discriminatory ability compared to currently available definitions of sorafenib-related adverse events, could be the optimal clinical marker to identify sorafenib responders with decreased risk of death by half.

Extracts of Cordyceps sinensis inhibit breast cancer cell metastasis via down-regulation of metastasis-related cytokines expression.

ETHNOPHARMACOLOGICAL RELEVANCE: Cordyceps sinensis is a traditional Chinese medicine and has been used as adjuvant treatments for cancer and it has been also demonstrated to be effective in cancer patients. AIM OF THE STUDY: The objective of the present study is to investigate the anti-metastasis effects of water extracts of Cordyceps sinensis (WECS) in breast cancer and the potential mechanisms. MATERIALS AND METHODS: The cytotoxicity of WECS on 4T1 breast cancer cells was evaluated in vitro using cell counting kit-8 (CCK8) assay. The in vivo anti-metastatic activity of intraperitoneally administered WECS and its effect on animal survival were measured in a mouse breast cancer metastasis model. To explore the molecular mechanisms of the anti-metastasis effect of WECS, the expression of matrix metalloprotein-9 (MMP-9) in serum was determined by enzyme-linked immunosorbent assay (ELISA). In addition, a protein array was used to examine the cytokine expression profiles in lung homogenates. RESULTS: Treatment with WECS (0.10-0.40mg/ml) significantly inhibited 4T1 cell viability in vitro. In animal studies, 50mg/kg WECS significantly reduced the number of metastatic lung nodules and the weight of lung, without affecting body weight of mice. Furthermore, WECS increased the survival rate of 4T1 tumor bearing mice in a dose dependent manner, and at high dose, WECS (50mg/kg) significantly increased the life span of the mice compared to untreated control group. The expression level of MMP-9 in serum was decreased about 50% in 50mg/kg WECS treated group compared to control group. The results of protein array showed that the expression of CC chemokine ligand 17 (CCL17), MMP-9, osteopontin (OPN), interleukin-33 (IL-33), CC chemokine ligand 12 (CCL12) and CC chemokine ligand 6 (CCL6) in the lungs of 4T1 tumor bearing mice was increased more than two fold compared with normal mice. Among them, the expression of CCL17, MMP-9, OPN, IL-33 was significantly reduced by treatment of 50mg/kg WECS. CONCLUSION: Our results demonstrated that WECS has potent anti-metastasis activity in a mouse breast cancer metastasis model possibly by down-regulation the expression of several metastasis-related cytokines.

mRECIST response combined with sorafenib-related adverse events is superior to either criterion alone in predicting survival in HCC patients treated with TACE plus sorafenib.

The mRECIST and dermatologic adverse events (AEs) can be used to assess the patient response to transarterial chemoembolization (TACE) and/or sorafenib for hepatocellular carcinoma (HCC). Here, we aimed to combine the two criteria to stratify the prognosis in patients with unresectable HCC receiving TACE plus sorafenib (TACE-S). In total, 176 consecutive HCC patients treated with TACE-S were enrolled. CT scans and laboratory tests were conducted pretreatment (at baseline, 5-7 days before the TACE-S) and post-treatment (at 1, 2 and 3 months). The radiological response was assessed according to mRECIST. Sorafenib-related AEs were recorded every 2 weeks after oral administration, and patients with dermatologic AEs of Grade 2 or more were defined as dermatologic responders. The earliest time at which mRECIST and dermatologic responses correlated with survival was 2 months after therapy. The mRECIST-dermatologic AE combination assessment stratified patients into three different prognoses; responders on both assessments exhibited the longest median overall survival (OS), followed by responders on one assessment and non-responders on both assessments (30.5, 17.4 and 8.3 months, respectively; p < 0.001). Achieving the highest C-index, the mRECIST-dermatologic AE combination showed better performance in predicting survival than either mRECIST or dermatologic AEs alone. Furthermore, the mRECIST-dermatologic AE combination remained a significant predictor of OS, even when the patients were stratified according to the BCLC stage, ECOG score or alpha-fetoprotein (AFP) value. This study showed that the combination of mRECIST response and dermatologic AEs is superior to either criterion used alone for predicting the survival of HCC patients treated with TACE-S.