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Atherosclerosis and the Cholesterol Theory: A Reappraisal

World Journal of Cardiovascular Diseases 2016年第11期6卷 391-409页

作者： Ang Peng Wong Abdul Latiff Mohamed aleksandra niedzwiecki Department of Graduate Studies Research and Commercialization Cyberjaya University College of Medical Sciences Cyberjaya Malaysia Dr. Rath Research Institute Santa Clara USA

Atherosclerosis is the precedent to ischemic heart disease, which may lead to angina, myocardial infarct, or heart failure;or to ischemic cerebrovascular disease, which may lead to stroke. The prevailing belief underlying conventional approaches to treatment of atherosclerosis and its sequel is that a diet high in cholesterol and saturated fat is the main contributory factor, triggering cholesterol build up in the intima of the blood vessels. Over the last 60 years, the blame has shifted from fats, to saturated fats, to low-density lipoprotein (LDL), and finally to oxidized LDL (Ox-LDL). Therapy has been predominantly aimed at lowering cholesterol and control of risk factors. However, there is an alternative hypothesis about the cause of heart disease linking it to the weakening of the vascular collagen matrix at the sites of high hemodynamic stress (coronary arteries) which triggers the infiltration of lipoprotein(apo) [Lp(a)] and plaque development. Accordingly, the vascular deposition of large molecules such as Lp(a) and atherosclerosis is the result of the body’s endogenous protective mechanism to reinforce the weakened artery walls. Understanding this mechanism may guide the natural prevention of this disease and form the basis for developing effective therapeutic strategies aiming at natural reversal of atherosclerosis through the reinforcement of the vascular wall structure as its primary goal. This reappraisal of atherosclerosis and the cholesterol theory looked at the historical development of the theory, and the Rath and Pauling unified theory of cardiovascular disease.

关键词： Atherosclerosis Low-Density Lipoprotein Oxidized Low-Density Lipoprotein Apolipoprotein

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Effect of a Nutrient Mixture on Fanconi Anemia Fibroblast and Normal Human Dermal Fibroblast: A Comparison

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Open Journal of Apoptosis 2016年第1期5卷 1-8页

作者： Mohd Waheed Roomi Tatiana Kalinovsky aleksandra niedzwiecki Matthias Rath Dr. Rath Research Institute Santa Clara CA USA

Fanconi anemia (FA) is a fatal heterogeneous autosomal recessive disorder, characterized by progressive bone marrow failure, congenital defect and cancer predisposition. Cell culture from FA fibroblast (FAF) displays certain abnormalities as compared to normal human dermal fibroblast (NHDF). This prompted us to investigate the effect of a specific nutrient mixture (NM) containing ascorbic acid, lysine, proline and green tea extract, which has demonstrated a broad spectrum of pharmacological activities, on FAF compared to NHDF. We investigated the in vitro effect of NM on FAF and NHDF cell proliferation by MTT assay, MMPs secretion by zymography, morphology by H&E staining and apoptosis by green caspase assay. FAF (FA-A: PD20, FA-A: PD220) and NHDF were cultured in modified Dulbecco Eagle media. At near confluence, the cells were treated with different concentrations of NM (0, 50, 100, 250, 500 and 1000 μg/ml) in triplicate. The cells were also treated with PMA to induce MMP-9 activity. NM had no effect on FAF cell viability in both cell lines compared to control. In contrast NM exhibited 20% at 50 and 100, 50% at 250, 60% at 500 and 70% toxicity at 1000 μg/ml on NHDF cells. Zymography demonstrated MMP-2 and MMP-9 on PMA stimulation in FAF and NM inhibited the activity of both MMP-2 and MMP-9 in a dose response fashion with total block at 500 μg/ml. In contrast, NHDF exhibited only MMP-2, both active and inactive forms, and NM inhibited their activities in a dose-dependent manner with total block at 1000 μg/ml. H&E staining did not indicate any morphological changes in FAF nor induced apoptosis at higher concentrations, as seen by caspases assay. However, although no morphological changes in NHDF were noted up to NM 100 μg/ml, progressive changes in cell shrinkage, rounding and nuclear condensation, pertaining to apoptosis, were observed at higher concentrations. These changes were consistent with the results from the green caspases apoptosis assay. Our data demonstr

关键词： Fanconi Anemia Fibroblasts Normal Human Dermal Fibroblasts Nutrients Cell Viability MMP-2 and 9 Apoptosis

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Induction of Apoptosis in the Human Prostate Cancer Cell Line DU-145 by a Novel Micronutrient Formulation

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Open Journal of Apoptosis 2015年第1期4卷 11-21页

作者： M. Waheed Roomi Neha Shanker aleksandra niedzwiecki Matthias Rath Oncology Division Dr. Rath Research Institute Santa Clara CA USA

Prostate cancer, the most frequently diagnosed cancer in men, primarily affects males aged 55 and older and is more common in African Americans than Caucasians. Once the cancer has metastasized, current treatments are generally ineffective. We have identified a novel anti-neoplastic agent, a specifically designed nutrient mixture (NM), containing ascorbic acid, lysine, proline and green tea extract that demonstrates a broad spectrum of anti-tumor activity against a number of human cancer cell lines. In a previous study NM significantly inhibited prostate tumor in nude mice. In this study, we tested whether the formulation exerts its anti-tumor effects through induction of apoptosis on prostate cancer cell line DU-145. The effect of the nutrient mixture (NM) on cell growth inhibition in DU-145 cells was examined by 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Morphological changes and caspase activation associated with apoptosis induction was checked by H&E staining and Live Green Caspase assay, respectively. The NM was found to be slightly toxic to DU-145 cells at 100 μg/ml, but significantly toxic at 500 μg/ml and 1000 μg/ml. Percentage of cells undergoing apoptosis also increased from 6% at 100 μg/ml to 49% at 500 μg/ml and 83% at 1000 μg/ml, with greater number of cells showing morphological changes such as condensed nuclei and an acidophilic cytoplasm at higher concentrations. For the purpose of comparison, NM was also tested on a normal human dermal fibroblast (NHDF) cell line which exhibited far less apoptosis induction as compared to DU-145 cells. The percentage of cells undergoing apoptosis in case of NHDF cells was 7% at 100 μg/ml, 25.6% at 500 μg/ml and 76.5% at 1000 μg/ml. Our results demonstrate that the NM is effective in inhibiting cancer cell viability and inducing apoptosis in prostate cancer DU-145 cells and can thus be used as an effective treatment for prostate cancer.

关键词： Prostate Cancer DU-145 NHDF Apoptosis Cytotoxicity Caspase MTT

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A Nutrient Mixture Inhibits MMP Secretion, Invasion, Growth, and Induction of Apoptosis in Human Tongue Cancer Cell Line SC-255

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Open Journal of Apoptosis 2013年第4期2卷 37-44页

作者： M. Waheed Roomi Nusrath W. Roomi Bilwa Bhanap aleksandra niedzwiecki Matthias Rath Dr. Rath Research Institute Oncology Division Santa Clara USA

A majority of oral cancers is squamous cell carcinoma and tongue carcinomas comprise 30% of all oral cancers. However, Phytochemicals, herbal and dietary antioxidants have been reported to prevent cancers. A nutrient mixture containing, ascorbic acid, lysine, proline and green tea extract, among other nutrients, has previously been shown to exhibit a broad spectrum chemo preventative and therapeutic anti-cancer properties in a number of cell lines. In a recent study, we found that the nutrient mixture significantly inhibited acetaminophen induced hepatic and renal toxicity, and it suppressed carbon tetrachloride induced hepatic toxicity in ICR mice as well. This study was undertaken to determine if the nutrient mixture is useful in inhibiting various parameters of cancer progression on human tongue cancer cell line SC-255. SC-255 cells were grown in a Dulbecco’s Eagle medium and treated with the nutrient mixture at 0, 10, 50, 100, 500 and 1000 μg/ml, in triplicate. The nutrient mixture exhibited 20% and 30% toxicity at 500 and 1000 μg/ml, respectively. Zymography demonstrated the expression of MMP-2 and MMP-9;and PMA treatment further enhanced MMP-9 activity. The nutrient mixture inhibited the secretion of MMP-2 and MMP-9 in a dose-dependent fashion with a total inhibition at 500 μg/ml. Matrigel invasion was significantly reduced by 40%, 80% and 100% at 100, 500 and 1000 μg/ml, respectively. The nutrient mixture also inhibited cell migration and induced apoptosis in a dose response fashion. Thus, the nutrient mixture may have a potential in the tongue cancer treatment.

关键词： Oral Cancer Nutrient Mixture MMP Apoptosis

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Metabolic dysfunction-associated steatotic liver disease:Navigating terminological evolution,diagnostic frontiers and therapeutic horizon-an editorial exploration

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World Journal of Gastroenterology 2024年第18期30卷 2387-2390页

作者： aleksandra Boldys Lukasz Buldak Department of Internal Medicine and Clinical Pharmacology School of Medicine in KatowiceMedical University of SilesiaKatowice 40-752Poland

Metabolic dysfunction-associated steatotic liver disease(MASLD),once known as non-alcoholic fatty liver disease(NAFLD),represents a spectrum of liver disorders characterized by lipid accumulation within *** redefinition of NAFLD in 2023 marked a significant reposition in terminology,emphasizing a broader understanding of liver steatosis and its associated *** is now recognized as a major risk factor for liver cirrhosis,hepatocellular carcinoma,and systemic complications such as cardiovascular diseases or systemic *** challenges arise,particularly in identifying MASLD in lean individuals,necessitating updated diagnostic protocols and investing in non-invasive diagnostic ***,there is an urgent need for effective treatments targeting MASLD,with emerging pharmacological options focusing on,among others,carbohydrate and lipid ***,understanding the roles of bile acid metabolism,the microbiome,and dietary interventions in MASLD pathogenesis and management holds promise for innovative therapeutic *** is a strong need to emphasize the importance of collaborative efforts in understanding,diagnosing,and managing MASLD to improve physicians’approaches and patient outcomes.

关键词： Metabolic dysfunction-associated steatotic liver disease Diagnostics Pathophysiology of metabolic dysfunction-associated steatotic liver disease Therapy of metabolic dysfunction-associated steatotic liver disease Therapeutic innovations

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Valorization of Tree Bark-Derived Suberin in Applications for the Bio-Based Composites Industry–A Recent Review

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Journal of Renewable Materials 2024年第6期12卷 1029-1042页

作者： aleksandra Jeżo Institute of Wood Sciences and Furniture SGGWNowoursynowska St.159Warsaw02-776Poland

Bark extracts are sustainable sources of biopolymers and hold great promise for replacing fossil fuel-based polymers,for example,in wood-based *** addition to primary and secondary metabolites,tree bark also contains suberin,which plays a major role in protecting the tree from environmental *** is a natural aliphatic-aromatic cross-linked polyester present in the cell walls of both normal and damaged external tissues,the main component of which are long-chain aliphatic *** main role as a plant ingredient is to protect against microbiological factors and water *** of the most important suberin monomers are suberin fatty acids,known for their hydrophobic and barrier ***,due to the diverse chemical composition of suberin,it is an attractive alternative to hydrocarbon-based *** its potential is recognized,it is not widely used in biocomposites technology,including wood-based composites and the polymer *** article will discuss the current knowledge about the potential of suberin and its components in biocomposites technology,which will include surface finishes,composite adhesives and polymer blends.

关键词： Suberin suberinic acids wood composites biocomposites biopolyester

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HIFs in hypoxic regulation of the extracellular matrix:focus on little-known player HIF-3

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BIOCELL 2024年第5期48卷 677-692页

作者： aleksandra GORNOSTAEVA LUDMILA BURAVKOVA MARGARITA LOBANOVA ELENA ANDREEVA Institute of Biomedical Problems of the Russian Academy of Sciences Khoroshevskoye Shosse 76AMoscow123007Russia

The structural and associated molecules of the extracellular matrix(ECM)complex is an important component of the local milieu of cells,both for maintaining their functions and *** is a dynamic structure that is finely tuned to changes in the *** of these factors is hypoxia,which can arise in tissues due to physiological or pathological *** a result of the hypoxic effect,the properties of the ECM are significantly modified,stiffness increases,the balance between degradation and synthesis of structural proteins shifts,and the deposition of biologically active mediators’***-inducible factors(HIFs)contribute significantly to the modification of the properties of the ECM under *** the three HIF isoforms,HIF-1 is the most studied,with numerous identified target genes encoding proteins that participate in all matrisome *** less is known about HIF-2 and *** the context of the effects of hypoxia on the matrisome,HIF-3 isoform is of particular *** the first two isoforms,transiently expressed during the first hours of hypoxia,HIF-3 is activated after around 24 h of exposure to hypoxia and persists for a longer *** addition,its transcription is more pronounced under hypoxia than are HIFs 1 and ***-3,rather than the first two isoforms,is possibly responsible for the changes that occur in matrisome during prolonged hypoxic *** review attempts to summarize the available data on the involvement of HIF-3 in the matrisome modification under hypoxia.

关键词： Hypoxia Hypoxia-inducible factors Matrisome

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Development and characterization of 3D-printed electroconductive pHEMA-co-MAA NP-laden hydrogels for tissue engineering

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Bio-Design and Manufacturing 2024年第3期7卷 262-276页

作者： Sara De Nitto aleksandra Serafin Alexandra Karadimou Achim Schmalenberger John J.EMulvihill Maurice N.Collins DIBRIS Polytechnic Inter-School Section University of Genoa16126 GenoaItaly School of Engineering Bernal InstituteUniversity of LimerickLimerick V94 T9PXIreland School of Natural Sciences Department of Biological SciencesUniversity of LimerickLimerick V94 T9PXIreland Health Research Institute University of LimerickLimerick V94 T9PXIreland AMBER University of LimerickLimerick V94 T9PXIreland

Tissue engineering(TE)continues to be widely explored as a potential solution to meet critical clinical needs for diseased tissue replacement and tissue *** this study,we developed a poly(2-hydroxyethyl methacrylate-co-methacrylic acid)(pHEMA-co-MAA)based hydrogel loaded with newly synthesized conductive poly(3,4-ethylene-dioxythiophene)(PEDOT)and polypyrrole(PPy)nanoparticles(NPs),and subsequently processed these hydrogels into tissue engineered constructs via three-dimensional(3D)*** presence of the NPs was critical as they altered the rheological properties during ***,all samples exhibited suitable shear thinning properties,allowing for the development of an optimized processing window for 3D *** were 3D printed into pre-determined disk-shaped configurations of 2 and 10 mm in height and diameter,*** observed that the NPs disrupted the gel crosslinking efficiencies,leading to shorter degradation times and compressive mechanical properties ranging between 450 and 550 *** conductivity of the printed hydrogels increased along with the NP concentration to(5.10±0.37)×10^(−7)S/*** vitro studies with cortical astrocyte cell cultures demonstrated that exposure to the pHEMA-co-MAA NP hydrogels yielded high cellular viability and proliferation ***,hydrogel antimicrobial studies with staphylococcus epidermidis bacteria revealed that the developed hydrogels affected bacterial *** together,these materials show promise for various TE strategies.

关键词： Conductive nanoparticles Hydroxyethyl methacrylate(HEMA) Ultraviolet(UV)polymerization 3D printing

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Physiological strategies in wild rodents:immune defenses of commensal rats

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Integrative Zoology 2024年第3期19卷 350-370页

作者： Ivana MIRKOV Dina TUCOVIC Jelena KULAS Anastasija MALESEVIC Dragan KATARANOVSKI Milena KATARANOVSKI aleksandra POPOV ALEKSANDROV Immunotoxicology Group Department of EcologyInstitute for Biological Research“Sinisa Stankovic”—National Institute of Republic of SerbiaUniversity of BelgradeBelgradeSerbia

The importance of issues associated with urban/commensal rats and mice(property damage,management costs,and health risks)press upon research on these *** the demography of commensal rodents is mostly studied,the need for understanding factors influencing their natural morbidity/mortality is also *** this respect,more attention is expected to be paid to immunity,the physiological mechanism of defense against host survival threats(pathogens,parasites,diseases).Commensal rats and mice carry numerous pathogens that evoke diverse immune *** state of immunity in commensal house mice is studied in great detail,owing to the use of laboratory strains in biomedical *** commensal rats are,compared to mice,carriers of more zoonotic agents,rats’immunity is studied mainly in that *** of these zoonotic agents cause chronic,asymptomatic infections,which justified studies of immunological mechanisms of pathogen tolerance versus clearance regulation in *** of some infections in specific tissues/organs pressed upon analysis of local/regional immune responses and/or immunopathology.A survey of immunological activity/responses in commensal rats is given in this review,with mention of existing data in commensal *** should throw some light on the factors relevant to their morbidity and lifespan,supplementing the knowledge of commensal rodent ecology.

关键词： commensal rats and mice immunopathology infection inflammation tolerance

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Polyelectrolyte Complexes between Hyperbranched and Linear Polysaccharides: Fucoidan/Chitosan

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Chinese Journal of Polymer Science 2024年第4期42卷 468-479页

作者： Ekaterina R.Gasilova Daria N.Poshina aleksandra O.Sitnikova Natalia N.Saprykina Yury A.Skorik Institute of Macromolecular Compounds of the Russian Academy of Sciences Bolshoi VO 31St.Petersburg199004Russian Federation

Polyelectrolyte complexes(PECs)of hyperbranched(HB)and linear polysaccharides are promising as more effective encapsulation agents compared to PECs formed by linear *** investigated the PECs between the HB anionic polysaccharide fucoidan(FUC)and the cationic linear polysaccharide chitosan(CS).The FUC had a molecular weight(MW)of 30×*** PECs were prepared in three solvents(water,0.01 and 0.1 mol/L acetic acid)with CS of MW of 15,110 and 170 kDa,and deacetylation degrees(DDA)of 70%and 97%.The structures of the PECs and the initial FUC were investigated by multi-angle static and dynamic light *** the FUC contained 18 wt%of—OSO3 groups and 5 wt%of uronic acid units,it was a“strong-weak”copolyanion,so the HB macromolecules of the FUC formed nanogel particles in 0.1 mol/L AcOH and open branched structures in water,as confirmed by the Kratky *** mixing the solutions of original components,the PEC structures underwent an equilibration period,the duration of which increased with the MW of *** the charge stoichiometry was approached,the PECs shrank;the fractal dimension approached unity,indicating the side-by-side packing of adjacent FUC branches with the help of *** aggregation in the vicinity of the charge compensation was hardly observed,as it occurred in a very narrow *** PEC content at theζ-potential inversion depended on solvents’pH and the DDA of *** the extreme case of core-shell PECs in 0.1 mol/L AcOH,obtained by mixing FUC nanogels with the solutions of high MW CS of 97%DDA,the protruding tails of CS formed a positively charged shell in the whole range of FUC content(10 wt%

关键词： Polyelectrolyte complexes Chitosan Hyperbranched fucoidan Light scattering

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