Interleukin-8 release by endothelial colony-forming cells isolated from idiopathic pulmonary fibrosis patients might contribute to their pathogenicityAbstractIntroductionIdiopathic pulmonary fibrosis (IPF) is a devastating disease characterized by obliteration of alveolar architecture, resulting in declining lung function and ultimately death. Pathogenic mechanisms involve a concomitant accumulation of scar tissue together with myofibroblasts activation and a strong abnormal vascular remodeling. Endothelial progenitor cells (ECFC subtype) have been investigated in several human lung diseases as a potential actor in IPF. We previously demonstrated that ECFCs are down-regulated in IPF in contrast to healthy controls. We postulated here that ECFCs might behave as a liquid biopsy in IPF patients and that they exert modified vasculogenic properties. Methods and resultsECFCs isolated from controls and IPF patients expressed markers of the endothelial lineage and did not differ concerning adhesion, migration, and differentiation in vitro and in vivo. However, senescent and apoptotic states were increased in ECFCs from IPF patients as shown by galactosidase staining, p16 expression, and annexin-V staining. Furthermore, conditioned medium of IPF-ECFCs had increased level of interleukin-8 that induced migration of neutrophils in vitro and in vivo. In addition, an infiltration by neutrophils was shown in IPF lung biopsies and we found in a prospective clinical study that a high level of neutrophils in peripheral blood of IPF patients was associated to a poor prognosis. ConclusionTo conclude, our study shows that IPF patients have a senescent ECFC phenotype associated with an increased IL-8 secretion potential that might contribute to lung neutrophils invasion during IPF. |
ADAM10 controls the differentiation of the coronary arterial endotheliumAbstractThe coronary vasculature is crucial for normal heart function, yet much remains to be learned about its development, especially the maturation of coronary arterial endothelium. Here, we show that endothelial inactivation of ADAM10, a key regulator of Notch signaling, leads to defects in coronary arterial differentiation, as evidenced by dysregulated genes related to Notch signaling and arterial identity. Moreover, transcriptome analysis indicated reduced EGFR signaling in A10ΔEC coronary endothelium. Further analysis revealed that A10ΔEC mice have enlarged dysfunctional hearts with abnormal myocardial compaction, and increased expression of venous and immature endothelium markers. These findings provide the first evidence for a potential role for endothelial ADAM10 in cardioprotective homeostatic EGFR signaling and implicate ADAM10/Notch signaling in coronary arterial cell specification, which is vital for normal heart development and function. The ADAM10/Notch signaling pathway thus emerges as a potential therapeutic target for improving the regenerative capacity and maturation of the coronary vasculature. |
Interleukin-22 promotes tumor angiogenesisAbstractTH17 cells play important yet complex roles in cancer development and progression. We previously reported that TH17 cells and IL-17 mediate resistance to anti-VEGF therapy by inducing recruitment of immunosuppressive and proangiogenic myeloid cells to the tumor microenvironment. Here, we demonstrate that IL-22, a key effector cytokine expressed by TH17 cells, directly acts on endothelial cells to promote tumor angiogenesis. IL-22 induces endothelial cell proliferation, survival, and chemotaxis in vitro and neovascularization in an ex vivo mouse choroid explant model. Blockade of IL-22, with a neutralizing antibody, significantly inhibits tumor growth associated with reduced microvascular density. No synergistic effect of IL-22 with VEGF was observed. These results identify IL-22 as a potential therapeutic target for blocking tumor angiogenesis. |
TSPYL5-mediated inhibition of p53 promotes human endothelial cell functionAbstractTestis-specific protein, Y-encoded like (TSPYL) family proteins (TSPYL1-6), which are members of the nucleosome assembly protein superfamily, have been determined to be involved in the regulation of various cellular functions. However, the potential role of TSPYL family proteins in endothelial cells (ECs) has not been determined. Here, we demonstrated that the expression of TSPYL5 is highly enriched in human ECs such as human umbilical vein endothelial cells (HUVECs) and human pluripotent stem cell-differentiated ECs (hPSC-ECs). Importantly, TSPYL5 overexpression was shown to promote EC proliferation and functions, such as migration and tube formation, by downregulating p53 expression. Adriamycin-induced senescence was markedly blocked by TSPYL5 overexpression. In addition, the TSPYL5 depletion-mediated loss of EC functions was blocked by p53 inhibition. Significantly, TSPYL5 overexpression promoted angiogenesis in Matrigel plug and wound repair in a mouse skin wound healing model in vivo. Our results suggest that TSPYL5, a novel angiogenic regulator, plays a key role in maintaining endothelial integrity and function. These findings extend the understanding of TSPYL5-dependent mechanisms underlying the regulation of p53-related functions in ECs. |
The regulatory network of miR-141 in the inhibition of angiogenesisAbstractThe miR-200 family, consisting of miR-200a/b/c, miR-141, and miR-429, is well known to inhibit epithelial-to-mesenchymal transition (EMT) in cancer invasion and metastasis. Among the miR-200 family members, miR-200a/b/c and miR-429 have been reported to inhibit angiogenesis. However, the role of miR-141 in angiogenesis remains elusive, as contradicting results have been found in different cancer types and tumor models. Particularly, the effect of miR-141 in vascular endothelial cells has not been defined. In this study, we used several in vitro and in vivo models to demonstrate that miR-141 in endothelial cells inhibits angiogenesis. Additional mechanistic studies showed that miR-141 suppresses angiogenesis through multiple targets, including NRP1, GAB1, CXCL12β, TGFβ2, and GATA6, and bioinformatics analysis indicated that miR-141 and its targets comprise a powerful and precise regulatory network to modulate angiogenesis. Taken together, these data not only demonstrate an anti-angiogenic effect of miR-141, further strengthening the critical role of miR-200 family in the process of angiogenesis, but also provides a valuable cancer therapeutic target to control both angiogenesis and EMT, two essential steps in tumor growth and metastasis. |
A ribosomal DNA-hosted microRNA regulates zebrafish embryonic angiogenesisAbstractMicroRNAs (miRNAs) are single-stranded small non-coding RNAs, generally 18–25 nucleotides in length, that act as repressors of gene expression. miRNAs are encoded by independent genes or processed from a variety of different RNA species. So far, there is no evidence showing that the ribosomal DNA-hosted microRNA is implicated in vertebrate development. Currently, we found a highly expressed small RNA hosted in ribosomal DNA was predicted as a novel miRNA, named miR-ntu1, in zebrafish endothelial cells by deep sequencing analysis. The miRNA was validated by custom-designed Taqman PCR, Northern Blot, and in silico analysis. Furthermore, we demonstrated that miR-ntu1 played a crucial role in zebrafish angiogenesis via modulation of Notch signaling. Our findings provide a notable case that a miRNA hosted in ribosomal DNA is involved in vertebrate development. |
Live imaging of angiogenesis during cutaneous wound healing in adult zebrafishAbstractAngiogenesis, the growth of new blood vessels from pre-existing vessels, is critical for cutaneous wound healing. However, it remains elusive how endothelial cells (ECs) and pericytes (PCs) establish new blood vessels during cutaneous angiogenesis. We set up a live-imaging system to analyze cutaneous angiogenesis in adult zebrafish. First, we characterized basic structures of cutaneous vasculature. In normal skin tissues, ECs and PCs remained dormant to maintain quiescent blood vessels, whereas cutaneous injury immediately induced angiogenesis through the vascular endothelial growth factor signaling pathway. Tortuous and disorganized vessel networks formed within a few weeks after the injury and subsequently normalized through vessel regression in a few months. Analyses of the repair process of injured single blood vessels revealed that severed vessels elongated upon injury and anastomosed with each other. Thereafter, repaired vessels and adjacent uninjured vessels became tortuous by increasing the number of ECs. In parallel, PCs divided and migrated to cover the tortuous blood vessels. ECs sprouted from the PC-covered tortuous vessels, suggesting that EC sprouting does not require PC detachment from the vessel wall. Thus, live imaging of cutaneous angiogenesis in adult zebrafish enables us to clarify how ECs and PCs develop new blood vessels during cutaneous angiogenesis. |
AutoTube: a novel software for the automated morphometric analysis of vascular networks in tissuesAbstractDue to their involvement in many physiologic and pathologic processes, there is a great interest in identifying new molecular pathways that mediate the formation and function of blood and lymphatic vessels. Vascular research increasingly involves the image-based analysis and quantification of vessel networks in tissue whole-mounts or of tube-like structures formed by cultured endothelial cells in vitro. While both types of experiments deliver important mechanistic insights into (lymph)angiogenic processes, the manual analysis and quantification of such experiments are typically labour-intensive and affected by inter-experimenter variability. To bypass these problems, we developed AutoTube, a new software that quantifies parameters like the area covered by vessels, vessel width, skeleton length and branching or crossing points of vascular networks in tissues and in in vitro assays. AutoTube is freely downloadable, comprises an intuitive graphical user interface and helps to perform otherwise highly time-consuming image analyses in a rapid, automated and reproducible manner. By analysing lymphatic and blood vascular networks in whole-mounts prepared from different tissues or from gene-targeted mice with known vascular abnormalities, we demonstrate the ability of AutoTube to determine vascular parameters in close agreement to the manual analyses and to identify statistically significant differences in vascular morphology in tissues and in vascular networks formed in in vitro assays. |
Kruppel-like factor 4 regulates developmental angiogenesis through disruption of the RBP-J–NICD–MAML complex in intron 3 of Dll4AbstractAngiogenesis is a multistep process that requires highly regulated endothelial cell (EC) behavior. The transcription factor Krüppel-like factor 4 (KLF4) is a critical regulator of several basic EC functions; we have recently shown that KLF4 disturbs pathological (tumor) angiogenesis by mediating the expression of members of VEGF and Notch signaling pathways. Notch signaling is central to orchestration of sprouting angiogenesis but little is known about the upstream regulation of Notch itself. To determine the role of KLF4 in normal (developmental) angiogenesis, we used a mouse retinal angiogenesis model. We found that endothelial-specific overexpression of KLF4 in transgenic mice (EC-K4 Tg) leads to increased vessel density, branching and number of tip cell filopodia as assessed on postnatal day 6 (P6). The hypertrophic vasculature seen with sustained KLF4 overexpression is not stable and undergoes prominent remodeling during P7–P12 resulting in a normal appearing retinal vasculature in adult EC-K4 Tg mice. We find that KLF4 inhibits Delta-like 4 (DLL4) expression in the angiogenic front during retinal vascular development. Furthermore, in an oxygen-induced retinopathy model, overexpression of KLF4 results in decreased vaso-obliteration and neovascular tuft formation that is similar to genetic or pharmacologic DLL4 inhibition. Mechanistically, we show that KLF4 disables the activity of the essential Notch transcriptional activator RBP-J by interfering with binding of co-activators NICD and MAML at intron 3 of the Notch ligand DLL4. In summary, our experimental results demonstrate a regulatory role of KLF4 in developmental angiogenesis through regulation of DLL4 transcription. |
Mouse models of Alzheimer's disease cause rarefaction of pial collaterals and increased severity of ischemic strokeAbstractVascular dysfunction contributes to the progression and severity of Alzheimer's disease (AD). Patients with AD also sustain larger infarctions after ischemic stroke; however, the responsible mechanisms are unknown. Pial collaterals are the primary source of protection in stroke. Unfortunately, natural aging and other vascular risk factors cause a decline in collateral number and diameter (rarefaction) and an increase in stroke severity. Herein, we tested the hypothesis that AD accelerates age-induced collateral rarefaction and examined potential underlying mechanisms. Triple and double transgenic mouse models of AD both sustained collateral rarefaction by 8 months of age, well before the onset of rarefaction caused by aging alone (16 months of age). Rarefaction, which did not progress further at 18 months of age, was accompanied by a twofold increase in infarct volume after MCA occlusion. AD did not induce rarefaction of similarly sized pial arterioles or penetrating arterioles. Rarefaction was minimal and occurred only at 18 months of age in a parenchymal vascular amyloid-beta model of AD. Rarefaction was not associated with amyloid-beta deposition on collaterals or pial arteries, nor was plaque burden or CD11b+ cell density greater in brain underlying the collateral zones versus elsewhere. However, rarefaction was accompanied by increased markers of oxidative stress, inflammation, and aging of collateral endothelial and mural cells. Moreover, rarefaction was lessened by deletion of CX3CR1 and prevented by overexpression of eNOS. These findings demonstrate that mouse models of AD promote rarefaction of pial collaterals and implicate inflammation-induced accelerated aging of collateral wall cells. Strategies that reduce vascular inflammation and/or increase nitric oxide may preserve collateral function. |
Πέμπτη 25 Απριλίου 2019
Angiogenesis
Gynecology and Obstetrics
| Uterus transplantation: advantages and disadvantages of a deceased donor |
Analysis of the reproductive outcomes and the size of the unicornuate uterus measured by magnetic resonance imaging and their relationshipAbstractPurposeTo evaluate the relationship between the uterine size measured by pelvic magnetic resonance and reproductive outcome in women with a unicornuate uterus. MethodsThis was a retrospective study including 140 patients affiliated with unicornuate uterus diagnosed by the pelvic MR prior to their first pregnancy in the Obstetrics and Gynecology Hospital of Fudan University from April 2010 to December 2017. All the length of the unicornuate uterus were re-measured and recorded by skilled radiologists during the study period. We divided all the 140 participants with complete pelvic MR imaging into four groups by the best reproductive outcomes, which refers to Group 1 (primary infertility, n = 21), Group 2 ( < 24 weeks' gestation, n = 34), Group 3 (preterm delivery, 24–35 weeks' gestation, n = 13), Group 4 ( ≥ 35 weeks' gestation, n = 72), followed them up and then analyzed the data. ResultsMeasurements of 140 patients with hemi-uteri were retrieved for analysis. The mean length of the uterine was 4.90 ± 0.56 cm. There were no significant differences in the uterine cavity length, cervical length, endometrial thickness and uterine wall thickness between the four groups while the uterine length (P = 0.001) was statistically significant. Women with uterine lengths ≥ 4.5 cm were more likely to experience full-term delivery compared with the other group (P = 0.001). Ordinal multiple logistic regression analysis showed that the uterine length [OR = 9.03 (95% CI: 2.90–28.13)] and uterine cavity length [OR = 0.32 (95% CI: 0.06–2.04)] were independent protective factors for better obstetric outcomes ConclusionThe uterine length is a reliable prognostic factor for the gestational week of delivery and an appropriate antenatal surveillance factor of women with unicornuate uterus. |
Compare two different usages of FRD for detecting high-grade cervical lesions and invasive cancerAbstractObjectiveTo evaluate two usages of the folate receptor-mediated staining solution (FRD) for detecting high-grade cervical lesions and invasive cancer, and compared with cytology test (TCT) and human papillomavirus (HPV) testing. MethodsFRD sampling and FRD direct staining methods were used for detecting high-grade cervical lesions and invasive cancer. As a comparison, TCT and HPV testing were also applied for screening high-grade cervical lesions and invasive cancer. The sensitivity and specificity of TCT, HPV testing, and staining results of FRD were analyzed by the SPSS software. ResultsIn this study, 317 patients with biopsy were collected. The positive rate of FRD sampling method was 35.33% (112/317), and positive rate of FRD direct staining was 48.90% (155/317). Area under the curve (AUC) of TCT, HPV testing, FRD sampling and FRD direct staining were 0.53, 0.55, 0.58, and 0.75, respectively. The sensitivity of TCT, HPV, FRD sampling and FRD direct staining was 69.72%, 97.25%, 64.22% and 81.65%, respectively, and the specificity was 37.98%, 12.98%, 79.81% and 68.27%, respectively. ConclusionCompared with TCT and HPV testing, two usages of FRD methods have compatible sensitivity and high specificity to detect high-grade cervical lesions and invasive cancer. FRD direct staining may be comfortable for routine cervical cancer screening |
Incisional hernias following open gynecological surgery: a population-based studyAbstractIntroductionIncisional hernia is a common and costly complication following abdominal surgery. The incidence of incisional hernia after gynecological surgery is not as well studied as that after general surgery. Materials and methodsThe Swedish National Quality Register for Gynecological Surgery (GynOp) collects preoperative, intraoperative, and postoperative information regarding gynecological surgery. Data were extracted from 2006 to 2014. The National Patient Register (NPR) contains physicians' data from both public and private hospitals. Univariate and multivariate Cox proportional hazard analyzes were performed on risk factors. ResultsBetween 2006 and 2014, 39,312 women undergoing open surgery were registered in GynOp. The NPR recorded 526 patients who were diagnosed with or had undergone surgery for incisional hernia. The mean follow-up was 2.8 years. Five years after surgery the cumulative incidence of incisional hernias was 2.0% (95% confidence interval 1.8–2.2%). In multivariate Cox proportional hazard analysis obesity (BMI > 30), age > 60 years, midline incision, smoking, kidney, liver, and pulmonary disease were found to predict an increased risk for incisional hernias (all p < 0.05). ConclusionsThere is much to be gained if the patient can cease smoking and lose weight before undergoing abdominal surgery. The Pfannenstiel incision results in fewer incisional hernias and should be considered whenever possible. |
Efficacy of a collagen-fibrin sealant patch (TachoSil®) as adjuvant treatment in the inguinofemoral lymphadenectomy for vulvar cancer: a double-blind randomized-controlled trialAbstractPurposeTo evaluate the effect of a collagen-fibrin sealant patch (TachoSil®) in preventing postoperative complications after inguinofemoral lymphadenectomy for vulvar cancer. MethodsDouble-blind randomized-controlled trial on consecutive patients undergoing bilateral inguinofemoral lymphadenectomy for vulvar cancer. Intraoperatively, inguinofemoral areas were randomized: one was treated with TachoSil®, while the contralateral had standard closure without collagen-fibrin sealant patch. Surgical outcomes, amount of drainage volume, duration of drain placement, and any postoperative complication (vulvar wound dehiscence, inguinal wound dehiscence, cellulitis, lymphangitis, lymphoceles, and hematoma) were recorded. Leg measurements were taken preoperatively and during postoperative follow-up until 6 months to evaluate lymphedema. ResultsA total of 19 patients were enrolled and 38 inguinofemoral dissections were performed. There was no significant difference between the investigational and control arm in the amount of drainage volume (p = 0.976), and duration of drain placement (p = 0.793). The postoperative complications, excluding lymphedema, were 10/19 (53%) in investigational arm and 9/19 (47%) in control arm (p = 0.74). At the end of follow-up, the prevalence of grade 1 lymphedema was 44.4% and 50% in investigational and control arm, respectively (p = 0.744); grade 2 and 3 lymphedema had a prevalence of 33.3% in both arms (p = 1). ConclusionApplication of TachoSil® does not seem to improve postoperative lymphorrhagia nor to reduce the incidence of postoperative complications in patients undergoing inguinofemoral lymphadenectomy for vulvar cancer. Considering this point, it would be useful to identify additional strategies in inguinofemoral dissection for the prevention of these complications. |
The impact of EndoPredict ® on decision making with increasing oncological work experience: can overtreatment be avoided?AbstractBackgroundEstimating distant recurrence risk in women with estrogen receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative early breast cancer is still challenging. EndoPredict® is a gene expression-based test predicting the likelihood of recurrent disease. We analyzed the difference in oncological decision making with and without the knowledge of gene expression tests. Patients and methodsThis is a retrospective analysis including patients diagnosed with hormone-receptor positive, Her2 negative breast cancer between 2011 and 2015 at the Municipal Breast Cancer Centre Cologne, Germany. All patients received an evaluation by EndoPredict®. An oncological tumor board (TB) with knowledge of these results served as a baseline (control group). This baseline was compared to the treatment decision (adjuvant chemotherapy yes vs. no) made by oncologists with different experience levels (less than 5 years, between 5 and 15 years, and more than 15 years) who were not provided the EndoPredict® scores. All clinicians had access to clinical as well to histopathological data. ResultsThere was no significant difference between control group and the oncologists with different experience levels concerning a chemotherapy indication. A trend could be shown in the subgroup of nodal negative patients between the treatment recommendation and physicians with more than 15 years of experience (p = 0.088). A further trend could be demonstrated in the subgroup of patients with a low Ki67 index (≤ 14%) (p = 0.063) between physician with 5–10 years of clinical experience and official treatment recommendation. ConclusionIt seems that inexperienced physicians may profit from the use of EndoPredict® to avoid an overtreatment. In nodal negative patients and patients with a low Ki67 index, undertreatment can be avoided with the use of EndoPredict® (borderline significance). Further prospective studies with larger study cohorts are needed to further validate this tool. |
Tumor cell-specific Serpin A1 expression in vulvar squamous cell carcinomaAbstractPurposeThe two main etiological factors for vulvar squamous cell carcinoma (vSCC) are the vulvar dermatosis lichen sclerosus (LS) and high-risk human papillomavirus (hrHPV). Serpin A1 (α1-antitrypsin) is a serine protease inhibitor, which plays a role in the tumorigenesis of various cancer types. The aim of the study was to evaluate the expressions of Serpin A1 in LS, premalignant vulvar lesions, and vSCC using immunohistochemistry (IHC) and serum analysis, and to compare Serpin A1 stainings to the tumor markers p53 and p16. MethodsIn total, 120 samples from 74 patients were studied with IHC for Serpin A1, p53 and p16: 18 normal vulvar skin, 53 LS, 9 premalignant vulvar lesions (dVIN/HSIL) and 40 vSCC samples. Serum concentrations of Serpin A1 were analyzed from 30 LS, 44 vSCC and 10 control patients. Expressions were compared to clinical data. ResultsTumor cell-specific Serpin A1 overexpression was detected in 88% of vSCC samples, independent of the etiology. The intensity of Serpin A1 expression was significantly higher in vSCC than in healthy vulvar skin, LS, or premalignant vulvar lesions. Serpin A1 showed an association with p53 positivity. No difference in overall survival was found between Serpin A1-, p53-, or p16-positive vSCC patients. Serum concentrations of Serpin A1 were equal in the LS, vSCC, and control groups. ConclusionTumor cell-specific Serpin A1 overexpression is a potential biomarker in vSCC. |
Effects of clarithromycin on inflammatory markers and clinical manifestations in postsurgical follow-up of patients with endometriosis: a double-blinded randomized placebo-controlled clinical trialAbstractPurposeStudies showed anti-inflammatory and immunomodulatory effects of macrolide antibiotics such as clarithromycin in endometriosis. Therefore, the present study aims to investigate the therapeutic efficacy of clarithromycin in patients with endometriosis. MethodsThis was a double-blinded randomized placebo-controlled trial conducted on endometriotic women during March 2016–2017 in Dena Hospital, Shiraz, Iran. Immediately after surgery, the patients were randomly divided into clarithromycin (real) (n = 120) and placebo group (n = 169). The real group received 500 mg of clarithromycin everyday for 6 months and the placebo group received the placebo. The serum levels of tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), Erythrocyte sedimentation rate (ESR) and C-reactive protein as well as clinical symptoms at baseline and 3 and 6 months of post-surgery were compared within and between groups. ResultsThe scores of dysmenorrhea, dyschezia, dyspareunia, and non-menstrual pain significantly decreased in both real and placebo groups compared with the baseline values. However, the real group showed greater reductions compared with the placebo group (p < 0.001). Similarly, the serum levels of CRP, TNF-α, and IL-10 decreased in both groups compared with the baseline values, but the real group showed greater reductions. Interestingly, the reductions in the clinical symptoms and serum levels did not significantly differ between the real and placebo groups. Moreover, the reductions in the studied variables showed no dependence on the time. ConclusionClarithromycin may be an appropriate treatment in endometriotic patients. However, the non-significant differences between the real and placebo groups necessitate further studies on the therapeutic efficacy of clarithromycin. |
Endoscopic surgery: talent or training?AbstractPurposeThere are two groups of undergraduate students involved in endoscopic surgery with different degrees of experience: average and more experience. This study proves whether the subjective impression of the laparoscopic trainer is verifiable and which factors influence extreme talent. Methods21 medical students of the eighth term of the University of Witten-Herdecke participated in the study. On their first course day, students got instructed in suturing and knot technique. They were then required to tie a maximum of five knots within 2 h. After a week, students repeated this procedure. Time used for tying knots was stopped. ResultsRegarding the time students used for their first knots, great differences were provable (7–8 min, average 23 min). However, an adaption of the knotting time was noticed at the end of the first course day. This was confirmed during the second course day. Neither acquired factors (music, sport, etc.) nor individual factors (visual acuity, handedness, etc.) had any impact on the time used for knotting. Merely, one advantage was seen with the first knots with the factors of playing the guitar and having a more than 10-h surgical previous experience. Knotting times leveled off at 95% to less than 10 min, though. DiscussionNeither normally talented nor extremely talented junior surgeons could be noticed, and so could not the co-factors providing an advantage or disadvantage for surgery, respectively. All prospective surgeons can learn defined tasks (knots) by short interval training, and thus show similarly good results after a few repetitions. |
Patients' perspectives towards malignant ascites: results of a prospective observational trial regarding expectations, characteristics and quality of life—a study of the North-Eastern-German Society of Gynecological OncologyAbstractPurposeMalignant ascites (MA) is a frequent and common symptom in (gyneco-) oncological patients. The present trial evaluated and assessed patients' characteristics, clinical features and the possible influence of MA on QoL measurements. MethodsA prospective observational trial was conducted from Oct 2013 until Nov 2016. Therefore an interdisciplinary questionnaire was developed. Overall 250 patients with histological confirmed MA were included with different cancer entities (gynecological, gastrointestinal). The correlation of MA caused symptoms and QoL measurements was assessed using Kendall's tau b. Multivariable logistic regression models were applied to analyze the risks of symptoms or severe limitation in daily activities. Results125 questionnaires could be analyzed. The majority of patients with MA had diagnosis of ovarian cancer (68.8%) and were under current cancer treatment (57.6%), mostly chemotherapy. Over 50% reported abdominal tension as major symptom, around 56% of the patients had MA when cancer was firstly diagnosed. Regression analysis showed that patients with MA above 2l were significantly more likely to be harmed in everyday activities. However, the age, gender, type of malignancy and the current treatment (chemotherapy vs. no chemotherapy) had no significant influence. ConclusionMA has a significantly impact on QoL measurements in cancer patients and might influence everyday activities including basic needs like eating, walking and body care. There is a high need for more information and education of patients with MA |
Oral Oncology
Herbal Medicine
| Acujoint™, a high efficient formulation with natural bioactives, exerts potent anti-arthritis effects in human osteoarthritis - A randomized clinical study Publication date: Available online 23 April 2019 Source: Journal of Herbal Medicine Author(s): Augustine Amalraj, Joby Jacob, Karthik Varma, Ajaikumar B. Kunnumakkara, Chandradhara Divya, Sreeraj Gopi AbstractThe aim of the study was to evaluate the efficacy and safety of Acujoint™ - a supplement for articular cartilage degradation- in the treatment of patients with Osteoarthritis (OA) by comparing it with glucosamine and chondroitin formulation, which is a popular supplement used to treat OA. Acujoint™ is a health supplement prepared with extracts of 3-O-acetyl-11-keto-β-boswellic acid from Boswellia serrata, β-Caryophyllene from Piper nigrum, aqueous extract of Kaempferia galangal and Cureit™ - a bioavailable curcumin formulation- in a fixed ratio based on complete natural matrix, which has been used to treat osteoarthritis. A randomized, double blind, active controlled, single centre, clinical study was carried out using Acujoint™ during 90 days of treatment in 24 patients (1:1 ratio) with symptoms of moderate to mild OA along with combination of Glucosamine (1500 mg) and Chondroitin (1200 mg). The study shows that Acujoint™ can provide significant improvement in relieving the symptoms and the pain associated with active OA between the groups as well as within the groups. Active OA patients, who received Acujoint™ at 250 mg per day for a treatment period of 90 days, reported statistically significant changes/decreases in their clinical symptoms and pain. This was evident from significant changes in the total Western Ontario and McMaster Universities Osteoarthritis index (WOMAC) score, pain score, functional ability score, visual analog scale (VAS) score and Lequesne functional index values at P < 0.05 level. Acujoint™ promises the beneficial effects for the treatment of human knee osteoarthritis by controlling inflammatory responses as well as the pain without any adverse effects. Graphical abstract |
| Antiplaque and antimicrobial efficacy of polyherbal mouth rinse among adult human volunteers – A short term randomized controlled trial Publication date: Available online 16 April 2019 Source: Journal of Herbal Medicine Author(s): BR Chandrashekar, Ramesh Nagarajappa, K Mruthunjaya, Suma Shekar, MS Girish, Rupesh Thakur AbstractSystematic evaluation of plant extracts and their combinations offers new insights into the development of innovative drugs from plants. The authors evaluated the antiplaque and antimicrobial efficacy of a polyherbal mouth rinse, using 0.2% chlorhexidine as positive and saline based mouth rinse as negative controls among adult human volunteers. Thirty eligible adult human volunteers were recruited and pre intervention prophylaxis was carried out to reduce their plaque scores to zero. Participants were randomly assigned to three different categories and given coded mouth rinse bottles containing either saline, a poly herbal mouth rinse containing Acacia nilotica, Murraya koenigii Linn Sprengel, Eucalyptus hybrid, and Psidium Guajava combined extracts at 1%, or 0.2% chlorhexidine. Participants were requested to use 10 ml of their assigned mouth rinse twice a day and refrain from oral hygiene practices for four days. On the fifth day following intervention, plaque buildup was assessed by a blinded investigator and supragingival plaque samples were collected. Unstimulated saliva samples were collected before and 60 minutes after mouth rinsing. Plaque samples were used in microbial assay, while saliva samples were used for assessing change in salivary pH. Post intervention plaque build-up, S. mutansand total viable counts were significantly higher in saline users compared to others, with no difference in salivary flow and pH. However, the difference between the polyherbal and chlorhexidine groups was not statistically significant. We conclude that the polyherbal mouth rinse merits further investigation as a potential alternative to chlorhexidine for preventing and controlling dental caries and plaque induced dental diseases. |
| Ethnopharmacological survey of plants used in the traditional treatment of pain conditions in Mali Publication date: Available online 11 April 2019 Source: Journal of Herbal Medicine Author(s): Ombeline Danton, Aimé Somboro, Baba Fofana, Drissa Diallo, Lassine Sidibé, Catherine Rubat-Coudert, Fabien Marchand, Alain Eschalier, Sylvie Ducki, Pierre Chalard AbstractPain is among the major concerns of healthcare authorities across the world. It is complicated to diagnose, manage and treat. Current western treatments are successful to some extent in relieving pain; they provide minimum improvements in terms of physical and emotional functioning and are often accompanied by side effects. Finding new solutions in pain management has thus become a priority. Natural products have always been a huge source of new active principles; traditional medicine is thus a key to innovation. In Mali, traditional remedies are more popular than pharmaceutical drugs but this knowledge, verbally transferred from generation to generation is at risk as younger generations are not taking over. Thus, this study was designed to identify plants that are used traditionally in the South of Mali for the treatment of painful conditions. Data was collected by means of semi-structured face-to-face interviews with traditional healers (N = 108) in the regions of Bamako, Sikasso and Dioïla. Two quantitative ethnopharmacological indexes were calculated: Relative Frequency of Citation (RFC) and Fidelity Level (FL) when RFC > 0.10. A total of 66 plant species distributed across 29 families were recorded during this two-month survey. Stomach aches and external pains were the most cited pain conditions followed by body pains and pain due to diseases such as diabetes and sickle cell disease. Cassia sieberiana DC. (RFC = 0,22), Zanthoxylum zanthoxyloides (Lam.) Zepren. & Timler (0,13), Pericopsis laxiflora(Benth.) Meeuwen (0,11), Flueggea virosa (Roxb. ex Willd) Royle (0,08) and Sarcocephalus latifolius (Sm.) E.A.Bruce (0,08) were the most cited plants. This ethnopharmacological survey provides preliminary data for the discovery of new analgesic molecules. Graphical abstract |
| Plant use as a traditional method by women against vaginal discharge in western Anatolia, Turkey: A qualitative research study Publication date: Available online 10 April 2019 Source: Journal of Herbal Medicine Author(s): Zekiye Turan, Eylem Toker, Mehtap Omaç Sönmez, Fatma Kutlar AbstractObjectiveThe aim of this research was to gain insight into the reasons why women useCyclamen coum. and how they use it, in addition to the symptoms being treated. Material and methodsThe study was carried out as a qualitative research. The first case was that of an inpatient with symptoms of vaginal infection who used Cyclamen coum. Snowball sampling was used for sample selection. Fifteen women were included in the research as users and proponents of this method. The questionnaire including socio-demographic attributes and an interview form were used to obtain in-depth information. After completion of interviews, raw research data were identified by a researcher, and these were then classified by three researchers in accordance with verified themes. This data was then reported using their interpretation. ResultsAll participants applied the treatment by placing theCyclamen coum. tuber into the vagina for a period of three days. The positive results obtained from experiences of traditional methods increases the extent to which women adopt this method. ConclusionPeople should be informed regarding the possible potential adverse consequences of the use of traditional methods. Also, further research should be performed on women's health and widely applied traditional applications. |
| Clinical efficacy of a topical polyherbal formulation in the management of fluorouracil -associated hand-foot syndrome Publication date: Available online 9 April 2019 Source: Journal of Herbal Medicine Author(s): Elnaz Karimi, Behrooz Gharib, Nematollah Rostami, Latifeh Navidpour, Minoo Afshar AbstractAimHand foot syndrome (HFS) is a common side effect following administration of fluoropyrimidine drugs like capecitabine and 5-flourouracil in cancer patients. This syndrome is not life threatening. However, it is the main reason for dose reduction or temporary discontinuation of these drugs. The aim of this study was evaluating the efficacy of a standardized topical polyherbal hydrogel (E.gel) containing Calendula officinalis L., Matricaria recutita L.and Salvia officinalis L. for the management of Hand Foot Syndrome (HFS) in cancer patients following administration of fluoropyrimidine drugs. MethodsIn the present survey, 27 patients suffering from HFS were randomized to receive the E.gel and the placebo four times a day for 2 weeks. At the baseline and at the end of trial HFS grades were determined. ResultsNo serious adverse events occurred. Among the patients who have completed the study, 71% had a significant improvement compared to the placebo (p-value = 0.039). In 5% of the patients no changes were observed in the treatment group, while the side effects had worsened in the placebo roup. Moreover, in 10% of the patients both treatment and placebo groups showed improvement and in 14% no changes were observed in both groups. ConclusionThis study shows that patients receiving the polyherbal hydrogel experienced less complications and symptoms associated with HFS. In summary, it seems that the use of the prepared polyherbal hydrogel was beneficial for cancer patients administered fluorouracil-chemotherapeutic agents. Graphical; abstract |
| Treating Depression Naturally: How Flower Essences can Help Rebalance your Life. Chris Phillips. Floris Books, Edinburgh, 2017, pp., £12.99/$19.95. ISBN 978-178250-427-6. Publication date: Available online 4 April 2019 Source: Journal of Herbal Medicine Author(s): Graeme Tobyn |
| Bioactive metabolites of Ganoderma lucidum: Factors, mechanism and broad spectrum therapeutic potential Publication date: Available online 3 April 2019 Source: Journal of Herbal Medicine Author(s): Chetan Sharma, Neha Bhardwaj, Anupam Sharma, Hardeep Singh Tuli, Priya Batra, Vikas Beniwal, Girish Kumar Gupta, Anil K. Sharma AbstractBackgroundThe global interest in edible medicinal herbs for healthcare has significantly increased during the last few years.Ganoderma lucidum is a medicinal mushroom which is known to be a potential source of many therapeutic and pharmaceutical products with significant health importance. MethodologyThe available literature using PubMed, Scopus and Google Scholar database was thoroughly reviewed using the keywords Natural Products,Ganoderma, secondary metabolites and therapeutics. Thisnarrative review of all the relevant papers with significant citations leads the authors to greater insight into the potential therapeutic significance of Ganoderma lucidum. ResultsThe presence of a wide array of secondary metabolites in this herb contributes to its pharmaceutical uses.G. lucidum is rich in polysaccharides (β-glucan,mannitol), alkaloids, and a group oftriterpenes (ganoderic acid). Many cellular mechanisms have been proposed to explain the mode of action of its active metabolites and their healthcare attributes including anticancer, antiviral, antioxidant and protective effects on liver and other secondary lymphoid organs. ConclusionThis review illustrates the broad spectrum therapeutic potential of secondary metabolites derived fromGanoderma and supports our understanding of the main pharmacologically active compounds present in this fungus. Insight into the actions of its secondary metabolites could further pave a way for establishing G. lucidum, as a pharmacologically important product. |
| Anti-inflammatory action of YHQ by regulating 5-LOX/COX-2/NF-κB/MAPKs/Akt signaling pathways in RAW 264.7 macrophage cells Publication date: Available online 3 April 2019 Source: Journal of Herbal Medicine Author(s): Bao-Hui Cheng, Tian-Yong Hu, Li Ma, Wen-Hui Hu, Yan-Yan Chen, Xian-Hai Zeng, Hai-Liang Zhao, Zhi-Qiang Liu, Shu-Qi Qiu AbstractYan-Hou-Qing (YHQ), a traditional Chinese medicine (TCM) formula including fifteen herbal medicines has been used for acute pharyngitis and cough treatment in Oriental medicine. However, anti-inflammatory activities of YHQ are poorly understood. The anti-inflammatory activities of YHQ were evaluated via enzyme-linked immunosorbent assay (ELISA), and the underlying mechanisms were further determined using western blot in lipopolysaccharide (LPS)-stimulated RAW 264.7 murine macrophage cells in vitro. Anti-inflammation study revealed that YHQ inhibits the release of prostaglandin E2 (PGE2) potently by suppressing the protein expression of cyclooxygenase-2 (COX-2) and leukotriene B4 (LTB4) by reducing arachidonate 5-lipoxygenase (5-LOX) in LPS-stimulated RAW 264.7 macrophages. Further study demonstrated that YHQ inhibits the production of the pro-inflammatory cytokines interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α in LPS-stimulated RAW 264.7 macrophages by attenuating the phosphorylation p65 subunit of nuclear factor-kappaB (NF-κB). The suppressive effects of YHQ on LPS-stimulated inflammatory cytokines and mediators can be attributed to the suppression of YHQ on the phosphorylation of Akt and c-Jun N-terminal kinases (JNK), extracellular signal-regulated kinase (ERK), and p38 MAPKs. This study suggested that YHQ can be a preventive and potent therapeutic candidate for the management of inflammatory-mediated immune disorders. Graphical abstract |
| Effect of Arctium lappa linne (Burdock) root tea consumption on lipid profile and blood pressure in patients with knee osteoarthritis Publication date: Available online 1 April 2019 Source: Journal of Herbal Medicine Author(s): Leila Maghsoumi-Norouzabad, Farideh Shishehbor, Reza Abed, Ahmad Zare Javid, Bina Eftekhar-Sadat, Beitollah Alipour AbstractBackgroundKnee Osteoarthritis (OA) is a common disabling joint disorder worldwide. This study was designed to evaluate the effect of burdock root tea consumption on lipid profile and blood pressure in patients with OA. MethodsIn this randomized, single-blind, placebo-controlled clinical trial 36 patients (10 males and 26 females) aged 50–70 years old suffering from bilateral knee Osteoarthritis were randomly divided into intervention and control groups. The routine treatment was considered for all patients during the study. The intervention group received 3 cups / day of Burdock root tea (2 g tea bags steeped in 150 ml of boiled water for 10 min) and control group received only 3 cups / day of boiled water (150 ml) 30 min after meals (breakfast, lunch, and dinner) for 6 weeks. Blood lipid profile and blood pressure were assessed at baseline and 6 weeks post intervention. ResultsTotal cholesterol (TC), LDL-C, TC/HDL-C, LDL-C/HDL-C ratios, systolic and diastolic blood pressure were significantly decreased post intervention. A significant increase in HDL-C level was observed in the intervention group. At the end of the study, there was a significant difference in LDL-C, HDL-C, TC/HDL-C, LDL-C/HDL-C ratios and diastolic blood pressure between two groups. ConclusionsIt is suggested that consumption of burdock root tea may improve lipid profile and blood pressure status in patients with knee OA. Further studies may need to confirm these effects. |
| Daily date vinegar consumption improves hyperlipidemia, β-carotenoid and inflammatory biomarkers in mildly hypercholesterolemic adults Publication date: Available online 18 March 2019 Source: Journal of Herbal Medicine Author(s): Zeshan Ali, Haile Ma, Asif Wali, Ishmael Ayim, Muhammad Nauman Sharif AbstractDates are delicious fruits with a sweet taste and a fleshy consistency. Dates also have various bioactive components which have effects on different types of diseases. The objective of this study was to determine the effects of date vinegar made from date pulp and pits on the serum lipid profile and inflammatory biomarkers of mildly hypercholesterolemic adults. Seventy-six subjects with mildly raised total cholesterol and LDL cholesterol were enrolled. Participants ingested 30 mL of either date vinegar or placebo daily together with their normal diets. Plasma lipids, inflammatory biomarkers, carotenoids, potassium, folic acid, urea and creatinine were measured at baseline after 4 weeks and after treatment. These results suggest that the date vinegar improved several serum lipid profile parameters (mg/dL: Total Cholesterol (TC) 246.40 ± 14.7 to 197.60 ± 14.7, P = 0.001; Low density lipoprotein (LDL) 166.6 ± 11.8 to 109.8 ± 11.8, P = 0.001; Triglycerides (TG) 170.30 ± 16.54 to 161.20 ± 17.8, P = 0.002; High density lipoprotein (HDL) 41.7 ± 8.08 to 44.1 ± 8.05, P = 0.003) and inflammatory biomarkers (C-reactive protein (CRP) 7.05 ± 1.23 to 4.12 ± 0.04 mg/L, P = 0.001; nitric oxide (NO) 31.06 ± 0.47 to 27.01 ± 0.14 μmol/L, P = 0.002; tumor necrosis factor alpha (TNFα) 17.2 ± 2.8 to 13.6 ± 2.4 pg/mL, P = 0.001; fibrinogen 272.54 ± 22.6 to 238.31 ± 11.7 mg/dL, P = 0.014). The findings suggest that date vinegar improved the concentration of lipid and inflammatory biomarkers. |