Traditional Chinese Medicine syndrome-related herbal prescriptions in treatment of malignant tumors

AbstractObjectiveTo investigate the distribution characteristics of TCM syndromes and the related herbal prescriptions for malignant tumors (MT).MethodsA clinical database of the TCM syndromes and the herbal prescriptions in treatment of 136 MT patients were established. The data were then analyzed using cluster and frequency analysis.ResultsAccording to the cluster analysis, the TCM syndromes in MT patients mainly included two patterns: deficiency of both Qi and Yin and internal accumulation of toxic heat. The commonly-prescribed herbs were Huangqi (Astraglus), Nüzhenzi (Fructus Ligustri Lucidi), Lingzhi (Ganoderma Lucidum), Huaishan (Dioscorea Opposita), Xiakucao (Prunella Vulgaris), and Baihuasheshecao (Herba Hedyotidis).ConclusionDeficiency of Qi and Yin is the primary syndrome of MT, and internal accumulation of toxic heat is the secondary syndrome. The herbs for Qi supplementation and Yin nourishment are mainly used, with the assistance of herbs for heat-clearance and detoxification

miR-17-5p and miR-106a are involved in the balance between osteogenic and adipogenic differentiation of adipose-derived mesenchymal stem cells

AbstractMesenchymal stem cells (MSCs) can differentiate into several distinct cell types, including osteoblasts and adipocytes. The balance between osteogenic and adipogenic differentiation is disrupted in several osteogenic-related disorders, such as osteoporosis. So far, little is known about the molecular mechanisms that drive final lineage commitment of MSCs. In this study, we revealed that miR-17-5p and miR-106a have dual functions in the modulation of human adipose-derived mesenchymal stem cells (hADSCs) commitment by gain- and loss-of-function assays. They could promote adipogenesis and inhibit osteogenesis. Luciferase reporter assay, western blot and ELISA suggested BMP2 was a direct target of miR-17-5p and miR-106a. Downregulation of endogeneous BMP2 by RNA interference suppressed osteogenesis and increased adipogenesis, similar to the effect of miR-17-5p and miR-106a upregulation. Moreover, the inhibitory effects of miR-17-5p on osteogenic and adipogenic differentiation of hADSCs could be reversed by BMP2 RNA interference. In conclusion, miR-17-5p and miR-106a regulate osteogenic and adipogenic lineage commitment of hADSCs by directly targeting BMP2, and subsequently decreased osteogenic TAZ, MSX2 and Runx2, and increased adipogenic C/EBPα and PPARγ

Regulation of CXCR4 expression in human mesenchymal stem cells by cytokine treatment: role in homing efficiency in NOD/SCID mice

Background and Objectives The use of mesenchymal stem cells (MSC) for cell therapy relies on the capacity of these cells to home and engraft long-term into the appropriate target tissue(s). Homing of MSC to bone marrow (BM) post-transplantation can occur, but does so with only poor efficiency. This study was designed to evaluate the role of the SDF-1/CXCR4 axis in the homing of Flk1+ MSC derived from human fetal BM.Design and Methods We investigated the expression of CXCR4 in Flk1+ MSC stimulated with a cytokine cocktail and explored their homing ability 24 hours after intravenous infusion into sublethally irradiated NOD/SCID mice. The peripheral blood was analyzed and human cells in recipients’ BM were quantified from 2 to 6 months after transplantation.Results We found that Flk1+ MSC harbored intracellular CXCR4 which can be rapidly induced to the cell surface within a few hours. Short-term (24 hours) stimulation with the cocktail of cytokines resulted in up-regulation of both cell surface and intracellular CXCR4, increasing in vitro migration capacity to SDF-1 and homing to the BM of irradiated NOD/SCID mice. Moreover, compared to non-treated cells, transplantation of cytokine-treated Flk1+ MSC resulted in faster hematologic recovery and higher levels of donor chimerism in BM. Neutralization of CXCR4 significantly reduced homing and engraftment of Flk1+ MSC in murine BM.Interpretation and Conclusions These results suggest that the SDF-1/CXCR4 axis plays an important role in the regulation of motility of Flk1+ MSC. Increasing CXCR4 expression might be a potential strategy to improve engraftment of MSC in BM and accelerate the recovery of hematopoiesis

Mesenchymal-stem-cell-based experimental and clinical trials: current status and open questions

Natural Science Foundation of Fujian Province [2009Y4001, 2008J1006]; Fujian Provincial Natural Science Fund [2006J0106]; Developmental Fund of Chen Keji Integrative Medicine [CKJ2010021]Introduction: Mesenchymal stem cells (MSCs) possess remarkable self-renewal ability and are able to differentiate into various cell lineages. MSCs can also enhance tissue repair and angiogenesis through a paracrine mechanism. It has been recognized that these cells hold great promise for tissue regeneration and treatment of immune-related diseases. Areas covered: This review aims at discussing the mechanisms of MSC-mediated immunomodulation and tissue repair and the related clinical trials, with special emphasis on factors that influence the efficiency of MSC-based therapy, including the source of MSCs, cell passage, cell dose, timing and route of administration. Expert opinion: MSCs may facilitate tissue repair through cell replacement and/or improving the microenvironment by releasing growth factors. Some of these factors also mediate the immunomodulatory effects of MSCs. It is important to establish global guidelines, protocols and standards for production and clinical trials of MSCs, so that MSCs can become a therapeutic agent with a reliable efficacy and good safety

Dendritic cell-based vaccination for renal cell carcinoma: challenges in clinical trials

Major Program of Natural Science Foundation of Fujian Province [2008J1006]After decades of research, dendritic cell (DC)-based vaccines for renal cell carcinoma have progressed from preclinical rodent models and safety assessments to Phase I/II clinical trials. DC vaccines represent a promising therapy that has produced measurable immunological responses and prolonged survival rates. However, there is still much room to improve in terms of therapeutic efficacy. The key issues that affect the efficiency and reliability of DC therapy include the selection of patients who will respond best to treatment, the proper preparation and administration of DC vaccines, and a combination of DC vaccination with other immune-enhancing therapies (e.g., removal of Tregs, CTLA-4 blockade and lymphodepletion). Additional antiangiogenic agents will hopefully lead to greater survival benefits for patients in early disease stages. This review focuses on the different approaches of DC-based vaccination against renal cell carcinoma and potential strategies to enhance the efficacy of DC vaccination

Nine-year follow-up of patients receiving recombinant human hepatocyte growth factor nude plasmid DNA for critical limb ischemia: Updated safety and efficacy results

CONTEXT: NL003 is a plasmid engineered to simultaneously express two isoforms of hepatocyte growth factor. The Phase II clinical trial shows that intramuscular injection of NL003 in the affected limb of patients with critical limb ischemia (CLI) is safe and could alleviate pain and promote ulcer healing. The purpose of this study was to evaluate the long-term safety and efficacy of NL003. METHODS: A total of 108 participants were evaluated: 32 in the placebo group and 76 in the NL003 group. The primary endpoint was 5-year amputation-free survival and the secondary endpoints were pain, ulcer, and adverse reactions. RESULTS: During a mean follow-up period of 10.4 years, the 5-year amputation-free survival rate was 67.1% (51/76) in the NL003 group and 37.5% (12/32) in the placebo group (P < 0.05). The median amputation-free survival was 9.53 years in the NL003 group and 4.51 years in the placebo group. There was no significant difference in the rates of major amputation between the two groups (21.1% vs. 21.9%). Pain relief and ulcer healing tended to favor the NL003 group. No serious adverse reactions such as gene integration and tumor were found during the follow-up. CONCLUSIONS: NL003 has a favorable long-term safety profile and may provide long-term benefit for patients with CLI

Mechanical stretching of pulmonary vein stimulates matrix metalloproteinase-9 and transforming growth factor-β1 through stretch-activated channel/MAPK pathways in pulmonary hypertension due to left heart disease model rats.

Pulmonary hypertension due to left heart disease (PH-LHD) is a momentous pulmonary hypertension disease, and left heart disease is the most familiar cause. Mechanical stretching may be a crucial cause of vascular remodeling. While, the underlining mechanism of mechanical stretching-induced in remodeling of pulmonary vein in the early stage of PH-LHD has not been completely elucidated. In our study, the PH-LHD model rats were successfully constructed. After 25 days, doppler echocardiography and hemodynamic examination were performed. In addition, after treatment, the levels of matrix metalloproteinase-9 (MMP-9) and transforming growth factor-β1 (TGF-β1) were determined by ELISA, immunohistochemistry and western blot assays in the pulmonary veins. Moreover, the pathological change of pulmonary tissues was evaluated by H&E staining. Our results uncovered that left ventricular insufficiency and interventricular septal shift could be observed in PH-LHD model rats, and the right ventricular systolic pressure (RVSP) and mean left atrial pressure (mLAP) were also elevated in PH-LHD model rats. Meanwhile, we found that MMP-9 and TGF-β1 could be highly expressed in PH-LHD model rats. Besides, we revealed that stretch-activated channel (SAC)/mitogen-activated protein kinases (MAPKs) signaling pathway could be involved in the upregulations of MMP-9 and TGF-β1 mediated by mechanical stretching in pulmonary vein. Therefore, current research revealed that mechanical stretching induced the increasing expressions of MMP-9 and TGF-β1 in pulmonary vein, which could be mediated by activation of SAC/MAPKs signaling pathway in the early stage of PH-LHD

Cell therapy with autologous mesenchymal stem cells-how the disease process impacts clinical considerations

Natural Science Foundation of Fujian Province [2010Y2006]; National Natural Science Foundation of China [81272922]The prospective clinical use of multipotent mesenchymal stromal cells (MSCs) holds enormous promise for the treatment of a large number of degenerative and age-related diseases. In particular, autologous MSCs isolated from bone marrow (BM) are considered safe and have been extensively evaluated in clinical trials. Nevertheless, different efficacies have been reported, depending on the health status and age of the donor. In addition, the biological functions of BM-MSCs from patients with various diseases may be impaired. Furthermore, medical treatments such as long-term chemotherapy and immunomodulatory therapy may damage the BM microenvironment and affect the therapeutic potential of MSCs. Therefore, a number of practical problems must be addressed before autologous BM-MSCs can be widely applied with higher efficiency in patients. As such, this review focuses on various factors that directly influence the biological properties of BM-MSCs, and we discuss the possible mechanisms of these alterations

Exploration of the mechanisms by which 3,4-benzopyrene promotes angiotensin II-induced abdominal aortic aneurysm formation in mice

ObjectiveThis study examined the influence of 3,4-benzopyrene (BaP), a compound found in cigarette smoke, on the formation of angiotensin II (Ang II)-induced abdominal aortic aneurysm (AAA) formation in mice and the underlying mechanisms.MethodsC57/B6n mice were divided into four groups. The control group received a weekly intraperitoneal injection of medium-chain triglycerides. The Ang II group received a daily Ang II infusion (0.72 mg/kg) and a weekly intraperitoneal injection of medium-chain triglycerides. The Ang II/BaP group received a daily Ang II infusion (0.72 mg/kg) and a weekly intraperitoneal BaP injection (10 mg/kg, dissolved in medium-chain triglycerides). The BaP group received a weekly intraperitoneal BaP injection (10 mg/kg). After 5 weeks, abdominal aortic diameter was determined. Aortic tissues underwent hematoxylin and eosin, Masson, and immunochemistry staining for evaluation of vascular wall structure, collagen, macrophage infiltration, matrix metalloproteinases (MMPs), and apoptosis.ResultsThe Ang II infusion and BaP injection induced AAAs in 41.67% of mice vs 25% in the Ang II group (P < .05). The average aortic diameter increased in the Ang II/BaP group compared with the Ang II group (1.40 ± 0.25 vs 1.2 ± 0.23 mm; P < .05). Average aortic muscular cell apoptosis was higher in the Ang II/BaP group (31% ± 12%) than in the Ang II (19% ± 5%; P < .05) or BaP groups (23% ± 4%; P < .05). Aortic macrophage infiltration and expression of MMP-2, MMP-9, MMP-12, and nuclear factor-κB increased (0.56 ± 0.12, 0.47 ± 0.13, 0.49 ± 0.14, 0.49 ± 0.11, and 0.42 ± 0.12, respectively) in the Ang II/BaP group compared with the Ang II group (0.27 ± 0.08, 0.25 ± 0.06, 0.24 ± 0.09, 0.24 ± 0.09, and 0.23 ± 0.06, respectively; P < .05 for all).ConclusionsBaP promotes Ang II-induced AAA formation in mice via elevating infiltration of macrophages, activating nuclear factor-κB, upregulating the expression of MMP-2, MMP-9, and MMP-12, and increasing the apoptosis of vascular muscle cells in its synergistic effect with Ang II in aortic wall.Clinical RelevanceAbdominal aortic aneurysm (AAA) is a potentially fatal condition for the adult population. Tobacco smoking has long been considered to be a notorious risk factor for AAA. A key component of cigarette smoke is 3,4-benzopyrene. We demonstrate that 3,4-benzopyrene may contribute to the pathogenesis of AAA, thus providing new evidence that tobacco is a risk factor for AAA

A Comparative Study of 3-Week and 6-Week Duration of Double-J Stent Placement in Rend Transplant Recipients

Purpose: To compare the efficiency and safety of 3-week and 6-week duration of double-J stent placement in patients who received a kidney transplant. Patients and Methods: Post-transplant recipients were divided into two groups. The duration of double-J stent placement was 6 weeks in group 1 (n = 186) and 3 weeks in group 2 (n = 179). Both groups received similar antibiotics and immunosuppressants. The double-J stents were removed cystoscopically under local anesthesia. The patients were followed up for at least 3 months. Urological complications were recorded, including urinary leakage, obstruction, and urinary tract infections. Results: There were no severe urological complications in both groups. Duration of 3 weeks was as effective as 6 weeks in preventing urological complications such as urinary leak and stenoses. There was no significant difference between the two groups in average duration of macroscopic hematuria, incidents of malposition of double-J stent and calculus formation in or around the stent. Compared with group 1, patients in group 2 had a lower incidence of urinary irritation and fewer urinary tract infection episodes. Conclusions: A shorter duration of double-J stent placement in renal transplantation recipients does not increase urological complications. In addition, it may decrease urinary tract infection and urinary irritation. copyright (C) 2012 S. Karger AG, Base