Antifungal Proteins with Antiproliferative Activity on Cancer Cells and HIV-1 Enzyme Inhibitory Activity from Medicinal Plants and Medicinal Fungi.

A variety of fungi, plants, and their different tissues are used in Traditional Chinese Medicine to improve health, and some of them are recommended for dietary therapy. Many of these plants and fungi contain antifungal proteins and peptides which suppress spore germination and hyphal growth in phytopathogenic fungi. The aim of this article is to review antifungal proteins produced by medicinal plants and fungi used in Chinese medicine which also possess anticancer and human immunodeficiency virus-1 (HIV-1) enzyme inhibitory activities.

Universal Health Coverage through Community Nursing Services: China vs. Hong Kong.

OBJECTIVE:: this article looks at how the development of community nursing services in China and Hong Kong can enhance universal health coverage. METHODS:: literature and data review have been utilized in this study. RESULTS:: nursing services have evolved much since the beginning of the nursing profession. The development of community nursing services has expanded the scope of nursing services to those in need of, not just hospital-level nursing care, but more holistic care to improve health and quality of life. CONCLUSION:: despite the one-country-two-systems governance and the difference in population and geography, Hong Kong and China both face the aging population and its complications. Community nursing services help to pave the road to Universal Health Coverage. OBJETIVO:: este artigo analisa a forma como o desenvolvimento de serviços de enfermagem comunitários na China e Hong Kong pode melhorar a cobertura universal de saúde. MÉTODOS:: literatura e revisão de dados foram utilizados neste estudo. RESULTADOS:: serviços de enfermagem têm evoluído muito desde o início da profissão de enfermagem. O desenvolvimento dos serviços de enfermagem da comunidade ampliou o escopo dos serviços de enfermagem, para aqueles que precisam não apenas de cuidados de enfermagem de nível de hospital, mas cuidados mais holísticos para melhorar a saúde e qualidade de vida. CONCLUSÃO:: apesar de ser "um-país-dois-sistemas" de governo, e as diferenças de população e geografia, Hong Kong e China enfrentam o envelhecimento da população e suas complicações. Os serviços de enfermagem da comunidade ajudam a pavimentar o caminho para a cobertura de saúde universal. OBJETIVO:: este artículo analiza cómo el desarrollo de los servicios de enfermería comunitaria en China y Hong Kong pueden expandir la cobertura universal de salud. MÉTODOS:: revisión de datos y literatura han sido utilizados en este estudio. RESULTADOS:: los servicios de enfermería han evolucionado mucho desde el comienzo de la profesión. El desarrollo de los servicios de enfermería comunitaria han ampliado el alcance de los servicios de enfermería a las personas que necesitan, no sólo en cuidados de enfermería en el hospital, sino también en una atención más integral para mejorar la salud y calidad de vida. CONCLUSIÓN:: a pesar del tipo de gobierno "un país, dos sistemas" y las diferencias de población y geografía, Hong Kong y China se enfrentan al envejecimiento de la población y sus complicaciones. Los servicios de enfermería comunitaria ayudan a allanar el camino hacia la cobertura universal de salud.

Universal Health Coverage through Community Nursing Services: China vs. Hong Kong / Cobertura Universal de Saúde através dos serviços de enfermagem comunitários: China vs. Hong Kong / Cobertura Universal de Salud a través de Servicios Comunitarios de Enfermería: China versus Hong Kong

ABSTRACT Objective: this article looks at how the development of community nursing services in China and Hong Kong can enhance universal health coverage. Methods: literature and data review have been utilized in this study. Results: nursing services have evolved much since the beginning of the nursing profession. The development of community nursing services has expanded the scope of nursing services to those in need of, not just hospital-level nursing care, but more holistic care to improve health and quality of life. Conclusion: despite the one-country-two-systems governance and the difference in population and geography, Hong Kong and China both face the aging population and its complications. Community nursing services help to pave the road to Universal Health Coverage.

RESUMO Objetivo: este artigo analisa a forma como o desenvolvimento de serviços de enfermagem comunitários na China e Hong Kong pode melhorar a cobertura universal de saúde. Métodos: literatura e revisão de dados foram utilizados neste estudo. Resultados: serviços de enfermagem têm evoluído muito desde o início da profissão de enfermagem. O desenvolvimento dos serviços de enfermagem da comunidade ampliou o escopo dos serviços de enfermagem, para aqueles que precisam não apenas de cuidados de enfermagem de nível de hospital, mas cuidados mais holísticos para melhorar a saúde e qualidade de vida. Conclusão: apesar de ser “um-país-dois-sistemas” de governo, e as diferenças de população e geografia, Hong Kong e China enfrentam o envelhecimento da população e suas complicações. Os serviços de enfermagem da comunidade ajudam a pavimentar o caminho para a cobertura de saúde universal.

RESUMEN Objetivo: este artículo analiza cómo el desarrollo de los servicios de enfermería comunitaria en China y Hong Kong pueden expandir la cobertura universal de salud. Métodos: revisión de datos y literatura han sido utilizados en este estudio. Resultados: los servicios de enfermería han evolucionado mucho desde el comienzo de la profesión. El desarrollo de los servicios de enfermería comunitaria han ampliado el alcance de los servicios de enfermería a las personas que necesitan, no sólo en cuidados de enfermería en el hospital, sino también en una atención más integral para mejorar la salud y calidad de vida. Conclusión: a pesar del tipo de gobierno “un país, dos sistemas” y las diferencias de población y geografía, Hong Kong y China se enfrentan al envejecimiento de la población y sus complicaciones. Los servicios de enfermería comunitaria ayudan a allanar el camino hacia la cobertura universal de salud.

Identification of Target Genes Involved in Wound Healing Angiogenesis of Endothelial Cells with the Treatment of a Chinese 2-Herb Formula.

Angiogenesis is vitally important in diabetic wound healing. We had previously demonstrated that a Chinese 2-herb formula (NF3) significantly stimulated angiogenesis of HUVEC in wound healing. However, the molecular mechanism has not yet been elucidated. In line with this, global expression profiling of NF3-treated HUVEC was performed so as to assess the regulatory role of NF3 involved in the underlying signaling pathways in wound healing angiogenesis. The microarray results illustrated that different panels of differentially expressed genes were strictly governed in NF3-treated HUVEC in a time-regulated manner. The microarray analysis followed by qRT-PCR and western blotting verification of NF3-treated HUVEC at 6 h revealed the involvement of various genes in diverse biological process, e.g., MAP3K14 in anti-inflammation; SLC5A8 in anti-tumorogenesis; DNAJB7 in protein translation; BIRC5, EPCAM, INSL4, MMP8 and NPR3 in cell proliferation; CXCR7, EPCAM, HAND1 and MMP8 in migration; CXCR7, EPCAM and MMP8 in tubular formation; and BIRC5, CXCR7, EPCAM, HAND1, MMP8 and UBD in angiogenesis. After 16 h incubation of NF3, other sets of genes were shown with differential expression in HUVEC, e.g., IL1RAPL2 and NR1H4 in anti-inflammation; miR28 in anti-tumorogenesis; GRIN1 and LCN1 in anti-oxidation; EPB41 in intracellular signal transduction; PRL and TFAP2A in cell proliferation; miR28, PRL and SCG2 in cell migration; PRL in tubular formation; and miR28, NR1H4 and PRL in angiogenesis. This study provided concrete scientific evidence in support of the regulatory role of NF3 on endothelial cells involved in wound healing angiogenesis.

MicroRNAs mediated targeting on the Yin-yang dynamics of DNA methylation in disease and development.

For decades, DNA methylation at the 5 position of cytosine (5mC) catalyzed by DNA methyltransferases (DNMTs) is a well-known epigenetic modification in mammalian genome, where it modulates chromatin remodeling and transcriptional silencing. The discovery of Ten-eleven translocation (TET) enzymes that oxidize 5mC to 5-hydroxymethylcytosine (5hmC) prompts a new era of DNA demethylation research. It is now established that in DNA demethylation pathway 5mC is first converted to 5-hydroxymethylcytosine (5hmC), then 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) through TETs. Conversion to unmethylated cytosine (5C) is further facilitated by excision mechanism through thymine-DNA glycosylase (TDG) or base excision repair (BER) pathway. Our understanding of DNMTs and TETs on epigenetic dynamics of cytosine methylation has led to a completion of the methylation (Yin) - demethylation (Yang) cycle on epigenetic modifications on cytosine. However, the regulations on DNA demethylation pathway remain largely unknown. In this review, we provide the recent advances on epigenetic dynamics of DNA demethylation and its potential control from the prespective of small non-coding RNA-mediated regulation. Specifically, we will illustrate how microRNAs contribute to active DNA demethylation control in normal and disease development based on recent findings in stem cells and cancer. This article is part of a Directed Issue entitled: Epigenetics dynamics in development and disease.

Enumeration and functional investigation of endothelial progenitor cells in neovascularization of diabetic foot ulcer rats with a Chinese 2-herb formula.

BACKBROUND: We investigated the effect of a Chinese 2-herb formula (NF3) on the enumeration and angiogenic differentiation of endothelial progenitor cells (EPCs) in diabetic foot ulcer rats. METHODS: EPCs and stromal cell-derived factor-1α (SDF-1α) were quantified by flow cytometry and ELISA, respectively. In vitro angiogenesis assays included proliferation, adhesion, migration and tube formation. RESULTS: Our result demonstrated that NF3 (0.98 g/kg) could significantly enhance the circulating CD34(+) /VEGFR2(+) /CD45(-) EPCs levels in diabetic foot ulcer rats by 60% (P < 0.05) through the partial elevation of SDF-1α, restoring the mobilization ability of EPCs for wound neovascularization. We successfully isolated the BM-derived EPCs to study their angiogenic potential after NF3 treatment. BM-derived EPCs significantly expressed cell surface markers of CD34, CD146 and VEGFR2 (P < 0.05 - 0.01). NF3 could significantly stimulate the proliferation and attachment ability of EPCs dose-dependently (P < 0.01-0.001). Besides, NF3 could significantly augment EPCs migration (P < 0.001) and tube formation (P < 0.01-0.001). CONCLUSIONS: NF3 modulated diabetic wound healing through regulation of systemic EPCs level and increase in local vascular formation.

Comprehensive proteomic analysis of a Chinese 2-herb formula (Astragali Radix and Rehmanniae Radix) on mature endothelial cells.

Endothelial cells are crucially involved in wound healing angiogenesis, restoring blood flow to wound tissues. Our previous study demonstrated that the Chinese 2-herb formula (NF3) possesses significant wound healing effect in diabetic foot ulcer rats with promising in vitro proangiogenic effects on human umbilical vein endothelial cells (HUVEC). Here, we present the comparative global proteome analysis of NF3-treated HUVEC in static or scratch conditions, screening the comprehensive molecular targets in governing the proangiogenic response in wound healing. Our results suggest plasminogen activator inhibitor-1, specifically down-regulated in static condition and Annexin A1 and Annexin A2, up-regulated in scratch condition, as principal proteins responsible for the proangiogenesis in wound healing. We also identified a panel of cytoskeleton regulatory proteins in static and scratch condition, mediating the migratory behavior of NF3-treated HUVEC. The key proteins in static state include myosin regulatory light polypeptide 9, SPAST, tropomyosin (TPM)2, and Vimentin while that in scratch state contained prelamin-A/C, TPM1, TPM2, and Vimentin. In addition, NF3 was shown to regulate transcription and translation, cell-cell interaction, and ROS defense in HUVEC. Proliferation and migration assays further confirmed the identified principal proteins plasminogen activator inhibitor-1 and Annexin A2 which are responsible for NF3-induced proangiogenesis of HUVEC in wound healing. This is the first study on the global proteome expression of NF3-treated HUVEC with the identification of the differences at the molecular level, between static and scratch conditions involved in wound healing angiogenesis.

A Chinese 2-herb formula (NF3) promotes hindlimb ischemia-induced neovascularization and wound healing of diabetic rats.

Diabetic foot ulcer is closely associated with peripheral vascular disease. Enhancement of tissue oxidative stress, reduction of nitric oxide (NO) and angiogenic growth factors, and abnormal matrix metalloproteinase (MMP) activity are pathophysiological factors in post-ischemic neovascularization and diabetic wound healing. Our previous study demonstrated that the Chinese 2-herb formula, NF3, showed significant wound healing effects on diabetic foot ulcer rats. A novel rat diabetic foot ulcer with hindlimb ischemia model was established in order to strengthen our claims on the diabetic wound healing and post-ischemic neovascularization effects of NF3. Our results demonstrate that NF3 can significantly reduce the wound area of the diabetic foot ulcer rat with hindlimb ischemia by 21.6% (p<0.05) compared with the control group. In addition, flow cytometric analysis revealed that NF3 could boost circulating EPC levels for local wound vessel incorporation. Immunohistochemical analysis showed that NF3 could significantly augment blood vessel density, VEGF and eNOS expression, and attenuate tissue oxidative stress of ischemic muscles (p<0.001). NF3 significantly stimulated MMP activity involved in angiogenesis. Our study shows, for the first time, the beneficial effects of NF3 in wound healing and post-ischemic neovascularization in diabetes.

Healing effect of a two-herb recipe (NF3) on foot ulcers in Chinese patients with diabetes: a randomized double-blind placebo-controlled study.

BACKGROUND: In the present study, we examined the effect of a two-herb traditional Chinese medicine (NF3), comprised of Astragali Radix and Radix Rehmanniae, on the healing of diabetic foot ulcer and the possible molecular mechanisms involved. METHODS: This was a prospective randomized double-blind placebo-controlled study. Sixteen diabetic patients were randomized to receive either placebo or NF3 for 6 months. Ulcer healing and sensory changes were examined. Molecular studies included measurement of serum tumor necrosis factor (TNF)-α and RNA microarray investigation. RESULTS: The daily rate of reduction in ulcer area was 3.55% in the NF3 group and 1.52% in the placebo group (P = 0.062). In the index limb, the number of negative tests for sensory neuropathy using monofilament was reduced from 27% to 7% in the NF3 group and from 37% to 35% in the placebo group (P < 0.001). In addition, NF3 significantly decreased serum TNF-α levels (P = 0.034). Microarray studies revealed concerted changes following NF3 treatment in the expression of genes implicated in fibroblast regeneration, angiogenesis, and anti-inflammation. CONCLUSIONS: In this proof-of-concept study, 6-month treatment with NF3 was associated with improved wound healing and sensation accompanied by concerted changes in gene expression.

Gene expression profiling on the molecular action of danshen-gegen formula in a randomized placebo-controlled trial of postmenopausal women with hypercholesterolemia.

The Danshen-Gegen formula (DG) is a traditional Chinese herbal formula which has long been used to treat cardiovascular disease. DG was found to be a cardiovascular tonic in our recent research. However, a comprehensive investigation of the molecular mechanism of DG in cardiovascular disease has not been performed. The aim of this study was to clarify the transcriptional profiling of genes modulated by DG on postmenopausal women by using DNAmicroarray technology. We obtained 29 whole blood samples both from DG-treated and placebo-treated subjects. Blood lipid profile and intima-media thickness (IMT) were measured. Affymetrix GeneChip was used to identify differentially expressed genes (DEGs), followed by validation by the real-time PCR method. The results showed that DG-treated group has a significant improvement in IMT and lipid profile as compared to placebo-treated group. For the genomic study, the DG-treated group has a higher number of DEGs identified as compared to the placebo-treated group. Two important biological processes of "regulation of systemic arterial blood pressure by hormone" and "regulation of smooth muscle proliferation" have been identified by GePS in the DG-treated group. No significant biological process and cellular components were identified in the placebo-treated group. This genomic study on the molecular action of DG in postmenopausal women gathered sufficient molecular targets and pathways to reveal that DG could improve neointima thickening and hypertension.

A herbal formula containing roots of Salvia miltiorrhiza (Danshen) and Pueraria lobata (Gegen) inhibits inflammatory mediators in LPS-stimulated RAW 264.7 macrophages through inhibition of nuclear factor κB (NFκB) pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: The herbal formula DG, containing roots of Salvia miltiorrhiza (Danshen) and Pueraria lobata (Gegen), has long history in treating cardiovascular diseases. It has been shown to be able to reduce intima-media thickening in coronary patients in our previous clinical study. Since intima-media thickening is the hallmark of atherosclerotic disease, the etiology of which is inflammation of the arterial wall, the mechanism underlying the effect of DG may be related to its anti-inflammatory activities. AIM OF STUDY: The present study aims to determine the anti-inflammatory activity of DG and elucidate its underlying mechanisms with regards to its molecular basis of action. MATERIALS AND METHOD: The anti-inflammatory effect of DG was studied by using lipopolysaccharide (LPS)-stimulated activation of nuclear factor κB (NFκB) pathway and subsequent production of inflammatory mediators, including nitric oxide (NO), prostaglandin E(2) (PGE(2)), interleukin-1 beta (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and macrophage chemotactic protein-1 (MCP-1), in mouse RAW 264.7 macrophages. RESULTS: The present study demonstrated that DG could suppress the production of NO and PGE(2) through the inhibition of iNOS and COX-2 genes. DG could also inhibit the production of IL-1ß, IL-6 and MCP-1, but not TNF-α, through the inhibition of respective mRNA expressions. Further investigations showed the inhibitory effect of DG on activation of IKKα/ß and degradation of IκBα, thus preventing nuclear translocation of NFκB. All these results suggested the inhibitory effects of DG on the production of inflammatory mediators through the inhibition of the NFκB pathway. CONCLUSIONS: The inhibitory effects of DG on the production of inflammatory mediators by LPS-stimulated RAW 264.7 macrophages, are accomplished by inhibiting the nuclear translocation of NFκB through inactivating IKKα/ß and preventing degradation of IκBα.

A novel function of differentiation revealed by cDNA microarray profiling of p75NTR-regulated gene expression.

The expression of the p75 neurotrophin receptor (p75NTR) is diminished in epithelial cells during progression of prostate cancer in vivo and in vitro. Previous studies have demonstrated a role for p75NTR as a tumor suppressor in prostate growth. To better understand the molecular mechanism of p75(NTR) on tumor suppression, we utilized a complementary deoxyribonucleic acid microarray composed of approximately 6,000 human cancer-related genes to determine the gene expression pattern altered by re-introduction of p75NTR into PC-3 prostate tumor cells. Comparison of the transcripts in the neo and p75NTR-transfected cells revealed 52 differentially expressed genes, of which 21 were up-regulated and 31 were down-regulated in the presence of p75NTR. Based on the known biological functions of the p75NTR-regulated genes, we observed that p75NTR modulated the expression of genes that are critically involved in the regulation of differentiation as well as cell adhesion, signal transduction, apoptosis, tumor cell invasion, and metastasis. Several differentially expressed genes identified by microarray were selected for confirmation using quantitative real-time polymerase chain reaction. Immunoblot analysis further confirmed increased cellular retinoic acid-binding protein I (CRABPI) and IGFBP5 protein levels and decreased level of PLAUR protein with increasing p75NTR protein expression. As CRABPI was elevated far more than any other genes, we observed that the retinoids, all-trans retinoic acid and 9-cis retinoic acid, that bind CRABPI, promoted nitroblue tetrazolium-associated functional cell differentiation in p75NTR PC-3 cells, but not in neo control PC-3 cells. Subsequent examination of the retinoic acid receptors (RARs) expression levels demonstrated an absence of RAR-beta in the neo control cells and re-expression in the p75NTR expressing cells, consistent with previous findings where RAR-beta is believed to play a critical role as a tumor suppressor gene that is lost during de-differentiation of prostate epithelial cells. Whereas the RAR-alpha and -gamma protein levels remained unchanged, retinoid X receptor (RXR)-alpha and -beta also exhibited increasing protein levels with re-expression of the p75NTR protein. Moreover, the ability of p75NTR siRNA to knockdown levels of RAR-beta, RXR-alpha, and RXR-beta supports the specificity of the functional involvement of p75NTR in differentiation. Hence, re-expression of the p75NTR appears to partially reverse de-differentiation of prostate cancer cells by up-regulating the expression of CRABPI for localized sequestration of retinoids that are available to newly up-regulated RAR-beta, RXR-alpha, and RXR-beta.