In vitro and in vivo antitumoral effects of combinations of polyphenols, or polyphenols and anticancer drugs: Perspectives on cancer treatment

Carcinogenesis is a multistep process triggered by genetic alterations that activate different signal transduction pathways and cause the progressive transformation of a normal cell into a cancer cell. Polyphenols, compounds ubiquitously expressed in plants, have anti-inflammatory, antimicrobial, antiviral, anticancer, and immunomodulatory properties, all of which are beneficial to human health. Due to their ability to modulate the activity of multiple targets involved in carcinogenesis through direct interaction or modulation of gene expression, polyphenols can be employed to inhibit the growth of cancer cells. However, the main problem related to the use of polyphenols as anticancer agents is their poor bioavailability, which might hinder the in vivo effects of the single compound. In fact, polyphenols have a poor absorption and biodistribution, but also a fast metabolism and excretion in the human body. The poor bioavailability of a polyphenol will affect the effective dose delivered to cancer cells. One way to counteract this drawback could be combination treatment with different polyphenols or with polyphenols and other anti-cancer drugs, which can lead to more effective antitumor effects than treatment using only one of the compounds. This report reviews current knowledge on the anticancer effects of combinations of polyphenols or polyphenols and anticancer drugs, with a focus on their ability to modulate multiple signaling transduction pathways involved in cancer

Nodes Effect on the Bending Performance of Laminated Bamboo Lumber Unit

This research studied the ultimate bearing capacity of laminated bamboo lumber (LBL) unit and thereby calculated the maximum bending moment. The load-displacement chart for all specimens was obtained. Then the flexural capacity of members with and without bamboo nodes in the middle section was coMPared. The bending experiment phenomenon of LBL unit was concluded. Different failure modes of bending components were analysed and concluded. Finally, the bending behaviour of LBL units is coMPared with other bamboo and timber products. It is shown that the average ultimate load of BS members is 866.1 N, the average flexural strength is 101 MPa, the average modulus of elasticity is 8.3 GPa, and the average maximum displacement is 17.02 mm. The average ultimate load of BNS members is 1008.1 N, the average flexural strength is 118.02 MPa, the average modulus of elasticity is 9.9 GPa, and the average maximum displacement is 18.26 mm. Laminated bamboo lumber (LBL) unit without bamboo nodes (BNS) has relatively higher flexural strength coMPared with LBL unit with bamboo nodes (BS). The presence of bamboo nodes reduces the strength of the entire structure. Three failure modes were concluded for BS members, and two failure modes were observed for BNS members during the experimental process. According to a coMParison between the LBL unit and other products, the flexural strength and bending modulus of elasticity of the LBL unit are similar as bamboo scrimber and raw bamboo components, which is much higher than timber components

Changes in serum levels of TNF-α, IL-6, OPG, RANKL and their correlation with radiographic and clinical assessment in fragility fractures and high energy fractures

Stages of bone turnover during fracture repair can be assessed employing serum markers of osteoblastic and osteoclastic activity, inflammatory cytokines, clinical evaluation and imaging instruments. Our study compare the fracture healing process in fragility fractures and high energy fractures by evaluating serum changes of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), osteoprotegerin (OPG) and receptor activator of the nuclear factor-kB ligand (RANKL) in combination with radiographic (Radiographic Union Scale for Tibial fractures, RUST) and clinical (Lower extremity measure, LEM) assessments. We enrolled 56 patients divided into four corresponding groups: group A with high energy trauma fracture (tibial/femoral shaft); group B with low energy trauma fracture (femoral fractures); healthy (control A) and osteoporotic subjects (control B). Blood samples were collected before surgery (T0) and after 10 weeks (T10). Serum concentrations of IL-6, TNF-α, RANKL and OPG were quantified using commercial enzyme-linked immunosorbent assay (ELISA) kits. Our results show that RANKL values are significantly higher at T10 than at T0 in low energy trauma fractures (group B). OPG is significantly lower in each control group than that of the respective fractured group and its concentration at T0 and at T10 is significantly lower in high than in low energy fractures. RANKL/OPG ratio is significantly higher in both controls than in fractured groups, and significantly increases after 10 weeks. IL-6 and TNF-α concentrations significantly decrease during fracture healing and are higher in high (group A) than in low energy fractures (group B). Significant differences were also found in both RUST score and LEM between groups A and B. Changes in TNF-α and IL-6 levels correlate with RUST and LEM in fragility and high energy fractures, while RANKL/OPG ratio is associated with these clinical parameters only in fragility fractures. These findings suggest that serum levels of IL-6, TNF-α, RANKL and OPG might be used to monitor the stages of fracture repair. Further studies will be needed to confirm the role of these cytokines in fracture repair

STRATEGI PENGEMBANGAN AGRIBISNIS KAKAO (STUDI KASUS DI DESA WOLOKISA KECAMATAN MAUPONGGO KABUPATEN NAGEKEO)

This research was conducted in Wolokisa Village, district of Mauponggo, Nagekeo Regency. This research aimed toidentify the strategies applied by farmers in developing cocoa farming,strengthand weakness, opportunities and threats factors indeveloping cocoa farming in Mauponggo district, Nagekeo Regency. Data collection interviews using questionnaires. Analysis of the data used is the SWOT analysis. The results showed that the internal factors influencing the development of the cocoa agribusiness in Wolokisa Village were (1) Availability of land and agro-climate, (2) Number of farmers, (3) Experience of farmers, (4) ) Cocoa quality, (5) Supporting institutions. (6) Farmers' weak management, (7) Simple technology that is still used (8) Poor acceleration (8) Pests and diseases. Although external factors that influence the development of the cocoa agribusiness in Wolokisa Village were: (1) high demand, (2) high prices, (3) clear market goals, (6) fluctuating prices, (7) climate, (8) cocoa producers from other villages. The appropriate strategies for developing cocoa agribusiness in Wolokisa Village are increasing production and better quality to meet demand and obtain high prices and using the experience of farmers and support institutions to reduce competitors

Optical one-way quantum computing with a simulated valence-bond solid

One-way quantum computation proceeds by sequentially measuring individual spins (qubits) in an entangled many-spin resource state. It remains a challenge, however, to efficiently produce such resource states. Is it possible to reduce the task of generating these states to simply cooling a quantum many-body system to its ground state? Cluster states, the canonical resource for one-way quantum computing, do not naturally occur as ground states of physical systems. This led to a significant effort to identify alternative resource states that appear as ground states in spin lattices. An appealing candidate is a valence-bond-solid state described by Affleck, Kennedy, Lieb, and Tasaki (AKLT). It is the unique, gapped ground state for a two-body Hamiltonian on a spin-1 chain, and can be used as a resource for one-way quantum computing. Here, we experimentally generate a photonic AKLT state and use it to implement single-qubit quantum logic gates.Comment: 11 pages, 4 figures, 8 tables - added one referenc

Segregation of Ni at early stages of radiation damage in NiCoFeCr solid solution alloys

Defect evolution under irradiation is investigated in a set of single-phase concentrated solid solution alloys (SP-CSAs) containing Ni with Co, Fe and/or Cr. We show that atomic segregation of Ni takes place already at very early stages of radiation damage in the 2-4 element SP-CSAs containing Fe or Cr, well below 1 dpa. We arrive at this conclusion by following the evolution of positron annihilation signals as a function of irradiation dose in single crystal samples, complemented by molecular dynamics simulations in the same model systems for high entropy alloys (HEAs). This manifestation of short-range order calls attention to composition fluctuations at the atomic level in irradiated HEAs. Ion irradiation may induce short-range order in certain alloys due to chemically biased elemental diffusion. The work highlights the necessity of updating the assumption of a totally random arrangement in the irradiated alloys, even though the alloys before irradiation have random arrangements of different chemical elements. (C) 2020 Acta Materialia Inc. Published by Elsevier Ltd.Peer reviewe

Autophagy induction extends lifespan and reduces lipid content in response to frataxin silencing in C. elegans

Severe mitochondria deficiency leads to a number of devastating degenerative disorders, yet, mild mitochondrial dysfunction in different species, including the nematode Caenorhabditis elegans, can have pro-longevity effects. This apparent paradox indicates that cellular adaptation to partial mitochondrial stress can induce beneficial responses, but how this is achieved is largely unknown. Complete absence of frataxin, the mitochondrial protein defective in patients with Friedreich's ataxia, is lethal in C. elegans, while its partial deficiency extends animal lifespan in a p53 dependent manner. In this paper we provide further insight into frataxin control of C. elegans longevity by showing that a substantial reduction of frataxin protein expression is required to extend lifespan, affect sensory neurons functionality, remodel lipid metabolism and trigger autophagy. We find that Beclin and p53 genes are required to induce autophagy and concurrently reduce lipid storages and extend animal lifespan in response to frataxin suppression. Reciprocally, frataxin expression modulates autophagy in the absence of p53. Human Friedreich ataxia-derived lymphoblasts also display increased autophagy, indicating an evolutionarily conserved response to reduced frataxin expression. In sum, we demonstrate a causal connection between induction of autophagy and lifespan extension following reduced frataxin expression, thus providing the rationale for investigating autophagy in the pathogenesis and treatment of Friedreich's ataxia and possibly other human mitochondria-associated disorders

Polyphenol-Mediated Autophagy in Cancer: Evidence of In Vitro and In Vivo Studies.

One of the hallmarks of cellular transformation is the altered mechanism of cell death. There are three main types of cell death, characterized by different morphological and biochemical features, namely apoptosis (type I), autophagic cell death (type II) and necrosis (type III). Autophagy, or self-eating, is a tightly regulated process involved in stress responses, and it is a lysosomal degradation process. The role of autophagy in cancer is controversial and has been associated with both the induction and the inhibition of tumor growth. Autophagy can exert tumor suppression through the degradation of oncogenic proteins, suppression of inflammation, chronic tissue damage and ultimately by preventing mutations and genetic instability. On the other hand, tumor cells activate autophagy for survival in cellular stress conditions. Thus, autophagy modulation could represent a promising therapeutic strategy for cancer. Several studies have shown that polyphenols, natural compounds found in foods and beverages of plant origin, can efficiently modulate autophagy in several types of cancer. In this review, we summarize the current knowledge on the effects of polyphenols on autophagy, highlighting the conceptual benefits or drawbacks and subtle cell-specific effects of polyphenols for envisioning future therapies employing polyphenols as chemoadjuvants

Polyphenol-mediated autophagy in cancer: Evidence of in vitro and in vivo studies

One of the hallmarks of cellular transformation is the altered mechanism of cell death. There are three main types of cell death, characterized by different morphological and biochemical features, namely apoptosis (type I), autophagic cell death (type II) and necrosis (type III). Autophagy, or self-eating, is a tightly regulated process involved in stress responses, and it is a lysosomal degradation process. The role of autophagy in cancer is controversial and has been associated with both the induction and the inhibition of tumor growth. Autophagy can exert tumor suppression through the degradation of oncogenic proteins, suppression of inflammation, chronic tissue damage and ultimately by preventing mutations and genetic instability. On the other hand, tumor cells activate autophagy for survival in cellular stress conditions. Thus, autophagy modulation could represent a promising therapeutic strategy for cancer. Several studies have shown that polyphenols, natural compounds found in foods and beverages of plant origin, can efficiently modulate autophagy in several types of cancer. In this review, we summarize the current knowledge on the effects of polyphenols on autophagy, highlighting the conceptual benefits or drawbacks and subtle cell-specific effects of polyphenols for envisioning future therapies employing polyphenols as chemoadjuvants

How Would Covid-19 Survivors Travel?: A Study on Travelling Behavior Bali Domestic Tourists

This study aims to discover how tourists whose background as COVID-19 survivors and the perceived health-related risks when traveling and how it affects their travel behavior in the future. This research is motivated by the lack of study on tourist traveling behavior, particularly from a specific segment of respondents. These respondents are tourists who were diagnosed positive for COVID-19 and have already recovered from it and are currently on vacation in two areas in Bali, Denpasar, and Badung. Sampling in this study is based on a purposive convenience sampling method through questionnaires distributed online and offline. In addition, The author uses Roscoe's Theory as a baseline in obtaining the minimum number of respondents, where a total of 100 respondents were gathered on the field. The author used multiple linear regression analysis to analyze the data collected from this research. The results of this study found that: (1) perceived health risks do not have a significant influence on future travel behavior; (2) tourists’ conditions as COVID-19 survivors have a significant influence on future travel behavior; and (3) simultaneously, health risks and tourists’ conditions as COVID-19 survivors influence future travel behavior. This study concludes that reducing perceived health risks and improving the health conditions of tourists as Covid-19 Survivors will improve their travel behavior in the future. The limitations of this study can also be used as suggestions for further research