Aleksandra Niedzwiecki - Academia.edu (original) (raw)

Papers by Aleksandra Niedzwiecki

PLOS ONE, Aug 30, 2023

The ongoing rise in antibiotic resistance, and a waning of the introduction of new antibiotics, h... more The ongoing rise in antibiotic resistance, and a waning of the introduction of new antibiotics, has resulted in limited treatment options for bacterial infections, including these caused by methicillin-resistant Staphylococcus aureus, leaving the world in a post-antibiotic era. Here, we set out to examine mechanisms by which theaflavin 3,3'-digallate (TF3) might act as an anti-hemolytic compound. In the presented study, we found that TF3 has weak bacteriostatic and bactericidal effects on Staphylococcus aureus, and strong inhibitory effect towards the hemolytic activity of its α-hemolysin (Hla) including its production and secretion. A supportive SPR assay reinforced these results and further revealed binding of TF3 to Hla with KD = 4.57×10 −5 M. Interestingly, TF3 was also able to protect human primary keratinocytes from Hla-induced cell death, being at the same time non-toxic for them. Further analysis of TF3 properties revealed that TF3 blocked Hla-prompting immune reaction by inhibiting production and secretion of IL1β, IL6, and TNFα in vitro and in vivo, through affecting NFκB activity. Additionally, we observed that TF3 also markedly attenuated S. aureusinduced barrier disruption, by inhibiting Hla-triggered E-cadherin and ZO-1 impairment. Overall, by blocking activity of Hla, TF3 subsequently subdued the inflammation and protected the epithelial barrier, which is considered as beneficial to relieving skin injury.

European journal of biology and biotechnology, Sep 12, 2021

InTech eBooks, Nov 2, 2011

Acquired immune deficiency syndrome (AIDS) has become a global health pandemic and the most commo... more Acquired immune deficiency syndrome (AIDS) has become a global health pandemic and the most common cause of death among young adults aged 20-24 years (Patton et al., 2009). According to the UN/AIDS Global Report published in November 2010 (UNAIDS 2010), about 1.8 million persons died from AIDS-related causes in the year 2009 alone. At the end of that year, the epidemic had left behind totally 16.6 million orphans, defined as those under 18 who had lost one or both parents to AIDS. Since the beginning of the epidemic, nearly 30 million people have died from AIDS-related causes. At the end of 2009, an estimated 30.8 million adults and 2.8 million children were living with HIV, the human immunodeficiency virus linked to AIDS; with women accounting for just over one-half of all adults living with HIV worldwide. During the same year, about 2.6 million persons became newly infected with HIV, including 370,000 children. Of all people living with HIV, about 68% reside in Sub-Saharan Africa (UNAIDS 2010). Despite these gruesome statistics, there is no cure in sight. Current treatment is based on the use of antiretroviral (ARV) drugs targeted against HIV at various steps in viral replication (Sleaseman and Goodenow 2003). Although ARV drugs can reduce viral load in the bloodstream, they neither cure HIV infection nor restore the immune system to combat AIDS (Roederer 1998, Pakker et al., 1998). Virus is known to persist indefinitely in reservoirs of latently-infected cells and emergence of drug-resistant strains is common. Furthermore, the effectiveness of ARVs in having any clinical benefits at all depends upon a number of factors, particularly the CD4 count and the nutritional status of patients at the point at which ARV treatment is commenced (Hong et al., 2001, Paton et al., 2006). Additionally, drugs are higly toxic and are often associated with adverse side effects to various organs of the body, including the bone marrow and liver, (

Experimental Oncology, Mar 22, 2016

Global journal of cancer therapy, Apr 9, 2019

Background: Malignant mesothelioma is a highly aggressive and fatal cancer of older people. Consi... more Background: Malignant mesothelioma is a highly aggressive and fatal cancer of older people. Consistently associated with asbestos exposure, mesothelioma is diagnosed when it is extensively metastasized and it has a dismal prognosis. Purpose of the study: Surgery, chemotherapy, and radiotherapy are the mainstay of treatment yet they are ineffective in increasing the mesothelioma patient survival. Therefore, a different approach is needed. A novel nutrient mixture containing green tea extract, ascorbic acid, lysine, and proline exhibited anti-cancer effects in various cancers. In our previous studies, the nutrient mixture was seen to block MMP secretion and invasion through Matrigel TM by mesothelioma cells. In the current study, we wanted to explore if the nutrient mixture could induce apoptosis in mesothelioma cells. Results and main fi ndings: The mesothelioma MSTO-211H cells were cultured in complete Ham F-12K medium and the cells were then treated with the nutrient mixture at 0-1000 μg/ml concentration. Cell cytotoxicity was measured by MTT assay, morphology by H&E staining, and the apoptosis by LIVE Green Caspases. The nutrient mixture did not show signifi cant inhibition of cell proliferation. However, H&E staining at the dose of 100 μg/ml showed a few cellular changes, while signifi cant changes pertaining to apoptosis morphology were observed at 500 and 1000 μg/ml. LIVE Green Caspases analysis showed cells in early an d late apoptosis with increasing doses of the nutrient mixture. Conclusions: Our results suggest that the nutrient mixture may provide a new supplemental strategy for enhancing the therapeutic options for mesothelioma

Scientific Reports

Fatty acids belong to a group of compounds already acknowledged for their broad antiviral efficac... more Fatty acids belong to a group of compounds already acknowledged for their broad antiviral efficacy. However, little is yet known about their effect on replication of human coronaviruses. To shed light on this subject, we first screened 15 fatty acids, three lipid-soluble vitamins, and cholesterol, on SARS-CoV-2 RdRp, and identified the four fatty acids with the highest RdRp inhibitory potential. Among them, linoleic acid was found to have the greatest interaction with SARS-CoV-2 RdRp, with its direct binding to the cavity formed by the RNA double helix and protein. Linoleic acid forms hydrophobic interactions with multiple residues, and at the same time forms electrostatic interactions including the hydrogen bond with Lys593 and Asp865. In line with these results, a dose-dependent inhibition of HCoV-OC43 replication in vitro was observed, additionally strengthened by data from in vivo study, which also confirmed anti-inflammatory potential of linoleic acid. Based on these results, w...

International Journal of Molecular Sciences

The cases of Lyme disease caused by Borrelia burgdorferi infection have been increasing throughou... more The cases of Lyme disease caused by Borrelia burgdorferi infection have been increasing throughout Northern America and Europe. This pathogen, if not treated in a timely manner with antibiotics, can cause persisting and debilitating health outcomes. In the search for novel agents against B. burgdorferi, we investigated a phenolic compound—gallic acid—for its anti-Borrelia and anti-inflammatory effects. Our results showed its biocidal effect starting from 100 μg/mL against active spirochetes, persisters/round-shaped bodies, and biofilm like aggregates of B. burgdorferi sensu stricto. Activation of macrophages by live B. burgdorferi also resulted in a robust NFκB-dependent proinflammatory responses seen in increased production of cytokines. Using human CD14+ macrophages in vitro, we showed that CD14+ adaptor and phosphorylated p65 molecule are impeded at nonbiocidal and noncytotoxic concentrations of gallic acid, resulting in the inhibition of both expression and secretion of cytokine...

American journal of cardiovascular disease, 2020

Vascular calcification is a pathophysiological process that is associated with coronary atheroscl... more Vascular calcification is a pathophysiological process that is associated with coronary atherosclerosis, and is a prognostic marker of cardiovascular morbidity and mortality. The process of arterial wall calcification is triggered and accompanied by pro-osteogenic phenotypical modifications of resident smooth muscle cells (SMC). Vitamin C (ascorbic acid) is an essential nutrient required to support the production of extracellular matrix components and maintain healthy connective tissue. In this study we investigated the effects of ascorbic acid on cultured human aortic SMC calcification process in vitro. Our results demonstrate that supplementation of SMC cultures with ascorbic acid significantly decreases calcium accumulation in SMC-produced and -deposited extracellular matrix. These effects were accompanied by a reduction in cell-associated alkaline phosphatase activity. Significantly, treatment of cultured SMC with HMG-CoA reductase inhibitors, simvastatin and mevastatin, resulte...

Experimental Oncology, 2021

Summary. Background: Uterine leiomyosarcoma is a rare malignant smooth muscle tumor originating i... more Summary. Background: Uterine leiomyosarcoma is a rare malignant smooth muscle tumor originating in the uterine wall that generally responds poorly to chemotherapy and radiation. Aim: We investigated the in vitro effects of a novel nutrient mixture containing lysine, proline, ascorbic acid, and green tea extract on the human leiomyosarcoma cell line SK-UT-1 by measuring cell proliferation, invasiveness, apoptosis, and expression of matrix metalloproteinases (MMP). We also tested the effects of nutrient mixture in vivo using nude mice. Materials and Methods: Human leiomyosarcoma SK-UT-1 cells were treated with different concentrations of nutrient mixture. Cell proliferation was determined by MTT assay; MMP expression by gelatinase zymography; invasion by Matrigel assay; migration by scratch test; apoptosis using Live Green caspase kit. In vivo studies were conducted on 5–6 weeks old female nude mice inoculated subcutaneously with 3 • 106 SK-UT-1 cells. The mice were fed a regular diet...

Scientific Reports, 2021

The strain SARS-CoV-2, newly emerged in late 2019, has been identified as the cause of COVID-19 a... more The strain SARS-CoV-2, newly emerged in late 2019, has been identified as the cause of COVID-19 and the pandemic declared by WHO in early 2020. Although lipids have been shown to possess antiviral efficacy, little is currently known about lipid compounds with anti-SARS-CoV-2 binding and entry properties. To address this issue, we screened, overall, 17 polyunsaturated fatty acids, monounsaturated fatty acids and saturated fatty acids, as wells as lipid-soluble vitamins. In performing target-based ligand screening utilizing the RBD-SARS-CoV-2 sequence, we observed that polyunsaturated fatty acids most effectively interfere with binding to hACE2, the receptor for SARS-CoV-2. Using a spike protein pseudo-virus, we also found that linolenic acid and eicosapentaenoic acid significantly block the entry of SARS-CoV-2. In addition, eicosapentaenoic acid showed higher efficacy than linolenic acid in reducing activity of TMPRSS2 and cathepsin L proteases, but neither of the fatty acids affecte...

PLOS ONE, 2021

In the pursuit of suitable and effective solutions to SARS-CoV-2 infection, we investigated the e... more In the pursuit of suitable and effective solutions to SARS-CoV-2 infection, we investigated the efficacy of several phenolic compounds in controlling key cellular mechanisms involved in its infectivity. The way the SARS-CoV-2 virus infects the cell is a complex process and comprises four main stages: attachment to the cognate receptor, cellular entry, replication and cellular egress. Since, this is a multi-part process, it creates many opportunities to develop effective interventions. Targeting binding of the virus to the host receptor in order to prevent its entry has been of particular interest. Here, we provide experimental evidence that, among 56 tested polyphenols, including plant extracts, brazilin, theaflavin-3,3’-digallate, and curcumin displayed the highest binding with the receptor-binding domain of spike protein, inhibiting viral attachment to the human angiotensin-converting enzyme 2 receptor, and thus cellular entry of pseudo-typed SARS-CoV-2 virions. Both, theaflavin-3...

PLOS ONE, 2019

In the search for novel agents against oral pathogens in their planktonic and biofilm form, we ha... more In the search for novel agents against oral pathogens in their planktonic and biofilm form, we have focused our attention on 10-undecynoic acid as the representative of the acetylenic fatty acids. Using macro-broth susceptibility testing method we first established MIC value. Next, the MBC value was determined from a broth dilution minimum inhibitory concentration test by sub-culturing it to BHI agar plates that did not contain the test agent. Anti-biofilm efficacy was tested in 96-well plates coated with saliva using BHI broth supplemented with 1% sucrose as a standard approach. Based on obtained results, MIC value for 10-undecynoic acid was established to be 2.5 mg/ml and the MBC value to be 5 mg/ml. The MBIC 90 showed to be 2.5 mg/ml, however completed inhibition of biofilm formation was achieved at 5.0 mg/ml. MBBC concentration revealed to be the same as MBC value, causing approximately 30% reduction at the same time in biomass of pre-existing biofilm, whereas application of 7.0 mg/ml of 10-undecynoic acid crossed the 50% eradication mark. Strong antiadherent effect was observed upon 10-undecynoic acid application at sub-MBC concentrations as well, complemented with suppression of acidogenicity and aciduricity. Thus, we concluded that 10-undecynoic acid might play an important role in the development of alternative or adjunctive antibacterial and anti-biofilm preventive and/or therapeutic approaches.

Tumori Journal, 2009

Aims and background Lung cancer, a leading cause of cancer death, is associated with exposure to ... more Aims and background Lung cancer, a leading cause of cancer death, is associated with exposure to inhalation carcinogens, most commonly those found in tobacco smoke. We investigated the in vivo effect of dietary supplementation with a nutrient mixture containing lysine, proline, arginine, ascorbic acid, green tea extract, N-acetyl cysteine, selenium, copper and manganese on the development of urethane-induced lung tumors in male A/J mice. Methods After one week of isolation, seven-week-old male A/J mice (n = 25) weighing 17–19 g were randomly divided into three groups: group A (n = 5), group B (n = 10), and group C (n = 10). Mice in groups B and C were each given a single intraperitoneal injection of urethane (1 mg/g body weight) in saline, whereas group A mice received an injection of saline alone. Groups A and B were fed a regular diet, whereas group C was fed the same diet supplemented with 0.5% nutrient mixture. After 20 weeks, mice were sacrificed, lungs were excised and weighed...

American journal of cardiovascular disease, 2016

Heart failure is a multifactorial disease with poor prognosis. There are many hypotheses regardin... more Heart failure is a multifactorial disease with poor prognosis. There are many hypotheses regarding the cause of heart failure. Leading among them are the hemodynamic and the neuro-hormonal hypotheses. Although the energy depletion hypothesis has been fairly recent, there is evidence suggesting that declining bioenergy plays a major role in heart failure. This review explored the myocardial energy depletion hypothesis from the role of micronutrients in correcting and alleviating symptoms of heart failure. Even though focus was on key nutrients such as coenzyme Q10, thiamine, riboflavin, L-carnitine, and taurine, emphasis was on the combined effect of multiple micronutrients as a whole. Search from databases from 2000 to 2015 produced four clinical studies using multiple micronutrients on heart failure. Evidence from the studies show that using high doses of multiple micronutrients may have positive effects on heart failure and simultaneously support the myocardial energy depletion hy...

World Journal of Cardiovascular Diseases, 2016

Atherosclerosis is the precedent to ischemic heart disease, which may lead to angina, myocardial ... more 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.

American journal of cardiovascular disease, 2016

Calcium, sodium and potassium channel blockers are widely prescribed medications for a variety of... more Calcium, sodium and potassium channel blockers are widely prescribed medications for a variety of health problems, most frequently for cardiac arrhythmias, hypertension, angina pectoris and other disorders. However, chronic application of channel blockers is associated with numerous side effects, including worsening cardiac pathology. For example, nifedipine, a calcium-channel blocker was found to be associated with increased mortality and increased risk for myocardial infarction. In addition to the side effects mentioned above by different channel blockers, these drugs can cause arterial wall damage, thereby contributing to vascular wall structure destabilization and promoting events facilitating rupture of plaques. Collagen synthesis is regulated by ascorbic acid, which is also essential for its optimum structure as a cofactor in lysine and proline hydroxylation, a precondition for optimum crosslinking of collagen and elastin. Therefore, the main objective in this study was to eva...

Experimental and Therapeutic Medicine, 2015

American journal of cardiovascular disease, 2015

Lipoprotein(a), a variant of LDL carrying the adhesive glycoprotein apo(a), is a leading risk fac... more Lipoprotein(a), a variant of LDL carrying the adhesive glycoprotein apo(a), is a leading risk factor for cardiovascular disease. Lipoprotein(a) (Lp(a)) is found in humans and subhuman primates but rarely in lower mammals. Better understanding of the evolutionary advantage of this molecule should elucidate its physiological role. We developed a new mouse model with two characteristics of human metabolism: the expression of Lp(a) and the lack of endogenous ascorbate (vitamin C) production. We show that dietary deficiency of ascorbate increases serum levels of Lp(a). Moreover, chronic hypoascorbemia and complete depletion of ascorbate (scurvy) leads to Lp(a) accumulation in the vascular wall and parallels atherosclerotic lesion development. The results suggest that dietary ascorbate deficiency is a risk factor for atherosclerosis independent of dietary lipids. We provide support for the concept that Lp(a) functions as a mobile repair molecule compensating for the structural impairment ...

The Open Natural Products Journal, 2008

Global incidence of tuberculosis, especially multiple-drug resistant tuberculosis, has been incre... more Global incidence of tuberculosis, especially multiple-drug resistant tuberculosis, has been increasing, despite development and use of various antimicrobial drugs for decades, leading to 2 million deaths a year. We evaluated the effect of micronutrient supplementation as an adjunct to standard treatment of patients with active pulmonary tuberculosis, on clinical improvement and frequency of adverse events on 120 patients aged 20 to 65 years diagnosed with active pulmonary tuberculosis at the Kiev Department of Phthisiatry. All participants (Test group) were prescribed standard medication supplemented with vitamin/essential nutrients. A Control group (n=100) of patients recently treated with standard medication alone at this facility were selected by matching to Test patients by stage of disease, confounding conditions, gender, and alcohol consumption. Standard clinical and diagnostic methods were applied to determine baseline values and at the termination of the study. After a two-month period of intensive chemotherapy, cavity healing (primary measure) occurred in 98% of the Test Group, but only in 69% of the Control Group. Furthermore, the Ziehl-Neelson sputum test was negative in 100% of the Test group, but only in 88% of the Control group. Resolution of respiratory compromise was higher in the Test group (87%) than in the Control group (78%). Furthermore, supplementation with vitamin/essential nutrients resulted in a significant decrease in the frequency and severity of adverse events from chemotherapy; only 11% in the Test group experienced adverse events while 46% did so in the Control group. In conclusion, clinical efficacy of chemotherapy was enhanced significantly with adjunctive use of nutrient supplementation. In addition, micronutrient supplementation decreased the frequency and severity of adverse effects from chemotherapy.

Molecular medicine reports

The incidence of type 2 diabetes mellitus is on the increase worldwide, with both environmental a... more The incidence of type 2 diabetes mellitus is on the increase worldwide, with both environmental and genetic factors implicated in its development. Diabetes is often preceded by metabolic syndrome (MS) and may develop in normal adults ingesting a high fructose diet. The effect of high fructose intake on the development of MS in children and adolescents is less clear. Our objective was to study the effects of a nutrient mixture and metformin (MET), a widely used oral diabetic medication, in modulating the physiological and biochemical parameters of a high fructose diet in immature mice. C57BL/6J wild‑type mice aged 7 weeks were administered 12% fructose in their water and MET in distilled water or a diabetic nutrient mix (DNM) over 7 weeks. DNM-fed mice showed a decrease in systolic blood pressure, total cholesterol and fructosamine compared to the fructose-fed only group (p<0.05). A discordant result was observed in the MET group, with a decrease in blood pressure but increases in...

PLOS ONE, Aug 30, 2023

The ongoing rise in antibiotic resistance, and a waning of the introduction of new antibiotics, h... more The ongoing rise in antibiotic resistance, and a waning of the introduction of new antibiotics, has resulted in limited treatment options for bacterial infections, including these caused by methicillin-resistant Staphylococcus aureus, leaving the world in a post-antibiotic era. Here, we set out to examine mechanisms by which theaflavin 3,3'-digallate (TF3) might act as an anti-hemolytic compound. In the presented study, we found that TF3 has weak bacteriostatic and bactericidal effects on Staphylococcus aureus, and strong inhibitory effect towards the hemolytic activity of its α-hemolysin (Hla) including its production and secretion. A supportive SPR assay reinforced these results and further revealed binding of TF3 to Hla with KD = 4.57×10 −5 M. Interestingly, TF3 was also able to protect human primary keratinocytes from Hla-induced cell death, being at the same time non-toxic for them. Further analysis of TF3 properties revealed that TF3 blocked Hla-prompting immune reaction by inhibiting production and secretion of IL1β, IL6, and TNFα in vitro and in vivo, through affecting NFκB activity. Additionally, we observed that TF3 also markedly attenuated S. aureusinduced barrier disruption, by inhibiting Hla-triggered E-cadherin and ZO-1 impairment. Overall, by blocking activity of Hla, TF3 subsequently subdued the inflammation and protected the epithelial barrier, which is considered as beneficial to relieving skin injury.

European journal of biology and biotechnology, Sep 12, 2021

InTech eBooks, Nov 2, 2011

Acquired immune deficiency syndrome (AIDS) has become a global health pandemic and the most commo... more Acquired immune deficiency syndrome (AIDS) has become a global health pandemic and the most common cause of death among young adults aged 20-24 years (Patton et al., 2009). According to the UN/AIDS Global Report published in November 2010 (UNAIDS 2010), about 1.8 million persons died from AIDS-related causes in the year 2009 alone. At the end of that year, the epidemic had left behind totally 16.6 million orphans, defined as those under 18 who had lost one or both parents to AIDS. Since the beginning of the epidemic, nearly 30 million people have died from AIDS-related causes. At the end of 2009, an estimated 30.8 million adults and 2.8 million children were living with HIV, the human immunodeficiency virus linked to AIDS; with women accounting for just over one-half of all adults living with HIV worldwide. During the same year, about 2.6 million persons became newly infected with HIV, including 370,000 children. Of all people living with HIV, about 68% reside in Sub-Saharan Africa (UNAIDS 2010). Despite these gruesome statistics, there is no cure in sight. Current treatment is based on the use of antiretroviral (ARV) drugs targeted against HIV at various steps in viral replication (Sleaseman and Goodenow 2003). Although ARV drugs can reduce viral load in the bloodstream, they neither cure HIV infection nor restore the immune system to combat AIDS (Roederer 1998, Pakker et al., 1998). Virus is known to persist indefinitely in reservoirs of latently-infected cells and emergence of drug-resistant strains is common. Furthermore, the effectiveness of ARVs in having any clinical benefits at all depends upon a number of factors, particularly the CD4 count and the nutritional status of patients at the point at which ARV treatment is commenced (Hong et al., 2001, Paton et al., 2006). Additionally, drugs are higly toxic and are often associated with adverse side effects to various organs of the body, including the bone marrow and liver, (

Experimental Oncology, Mar 22, 2016

Global journal of cancer therapy, Apr 9, 2019

Background: Malignant mesothelioma is a highly aggressive and fatal cancer of older people. Consi... more Background: Malignant mesothelioma is a highly aggressive and fatal cancer of older people. Consistently associated with asbestos exposure, mesothelioma is diagnosed when it is extensively metastasized and it has a dismal prognosis. Purpose of the study: Surgery, chemotherapy, and radiotherapy are the mainstay of treatment yet they are ineffective in increasing the mesothelioma patient survival. Therefore, a different approach is needed. A novel nutrient mixture containing green tea extract, ascorbic acid, lysine, and proline exhibited anti-cancer effects in various cancers. In our previous studies, the nutrient mixture was seen to block MMP secretion and invasion through Matrigel TM by mesothelioma cells. In the current study, we wanted to explore if the nutrient mixture could induce apoptosis in mesothelioma cells. Results and main fi ndings: The mesothelioma MSTO-211H cells were cultured in complete Ham F-12K medium and the cells were then treated with the nutrient mixture at 0-1000 μg/ml concentration. Cell cytotoxicity was measured by MTT assay, morphology by H&E staining, and the apoptosis by LIVE Green Caspases. The nutrient mixture did not show signifi cant inhibition of cell proliferation. However, H&E staining at the dose of 100 μg/ml showed a few cellular changes, while signifi cant changes pertaining to apoptosis morphology were observed at 500 and 1000 μg/ml. LIVE Green Caspases analysis showed cells in early an d late apoptosis with increasing doses of the nutrient mixture. Conclusions: Our results suggest that the nutrient mixture may provide a new supplemental strategy for enhancing the therapeutic options for mesothelioma

Scientific Reports

Fatty acids belong to a group of compounds already acknowledged for their broad antiviral efficac... more Fatty acids belong to a group of compounds already acknowledged for their broad antiviral efficacy. However, little is yet known about their effect on replication of human coronaviruses. To shed light on this subject, we first screened 15 fatty acids, three lipid-soluble vitamins, and cholesterol, on SARS-CoV-2 RdRp, and identified the four fatty acids with the highest RdRp inhibitory potential. Among them, linoleic acid was found to have the greatest interaction with SARS-CoV-2 RdRp, with its direct binding to the cavity formed by the RNA double helix and protein. Linoleic acid forms hydrophobic interactions with multiple residues, and at the same time forms electrostatic interactions including the hydrogen bond with Lys593 and Asp865. In line with these results, a dose-dependent inhibition of HCoV-OC43 replication in vitro was observed, additionally strengthened by data from in vivo study, which also confirmed anti-inflammatory potential of linoleic acid. Based on these results, w...

International Journal of Molecular Sciences

The cases of Lyme disease caused by Borrelia burgdorferi infection have been increasing throughou... more The cases of Lyme disease caused by Borrelia burgdorferi infection have been increasing throughout Northern America and Europe. This pathogen, if not treated in a timely manner with antibiotics, can cause persisting and debilitating health outcomes. In the search for novel agents against B. burgdorferi, we investigated a phenolic compound—gallic acid—for its anti-Borrelia and anti-inflammatory effects. Our results showed its biocidal effect starting from 100 μg/mL against active spirochetes, persisters/round-shaped bodies, and biofilm like aggregates of B. burgdorferi sensu stricto. Activation of macrophages by live B. burgdorferi also resulted in a robust NFκB-dependent proinflammatory responses seen in increased production of cytokines. Using human CD14+ macrophages in vitro, we showed that CD14+ adaptor and phosphorylated p65 molecule are impeded at nonbiocidal and noncytotoxic concentrations of gallic acid, resulting in the inhibition of both expression and secretion of cytokine...

American journal of cardiovascular disease, 2020

Vascular calcification is a pathophysiological process that is associated with coronary atheroscl... more Vascular calcification is a pathophysiological process that is associated with coronary atherosclerosis, and is a prognostic marker of cardiovascular morbidity and mortality. The process of arterial wall calcification is triggered and accompanied by pro-osteogenic phenotypical modifications of resident smooth muscle cells (SMC). Vitamin C (ascorbic acid) is an essential nutrient required to support the production of extracellular matrix components and maintain healthy connective tissue. In this study we investigated the effects of ascorbic acid on cultured human aortic SMC calcification process in vitro. Our results demonstrate that supplementation of SMC cultures with ascorbic acid significantly decreases calcium accumulation in SMC-produced and -deposited extracellular matrix. These effects were accompanied by a reduction in cell-associated alkaline phosphatase activity. Significantly, treatment of cultured SMC with HMG-CoA reductase inhibitors, simvastatin and mevastatin, resulte...

Experimental Oncology, 2021

Summary. Background: Uterine leiomyosarcoma is a rare malignant smooth muscle tumor originating i... more Summary. Background: Uterine leiomyosarcoma is a rare malignant smooth muscle tumor originating in the uterine wall that generally responds poorly to chemotherapy and radiation. Aim: We investigated the in vitro effects of a novel nutrient mixture containing lysine, proline, ascorbic acid, and green tea extract on the human leiomyosarcoma cell line SK-UT-1 by measuring cell proliferation, invasiveness, apoptosis, and expression of matrix metalloproteinases (MMP). We also tested the effects of nutrient mixture in vivo using nude mice. Materials and Methods: Human leiomyosarcoma SK-UT-1 cells were treated with different concentrations of nutrient mixture. Cell proliferation was determined by MTT assay; MMP expression by gelatinase zymography; invasion by Matrigel assay; migration by scratch test; apoptosis using Live Green caspase kit. In vivo studies were conducted on 5–6 weeks old female nude mice inoculated subcutaneously with 3 • 106 SK-UT-1 cells. The mice were fed a regular diet...

Scientific Reports, 2021

The strain SARS-CoV-2, newly emerged in late 2019, has been identified as the cause of COVID-19 a... more The strain SARS-CoV-2, newly emerged in late 2019, has been identified as the cause of COVID-19 and the pandemic declared by WHO in early 2020. Although lipids have been shown to possess antiviral efficacy, little is currently known about lipid compounds with anti-SARS-CoV-2 binding and entry properties. To address this issue, we screened, overall, 17 polyunsaturated fatty acids, monounsaturated fatty acids and saturated fatty acids, as wells as lipid-soluble vitamins. In performing target-based ligand screening utilizing the RBD-SARS-CoV-2 sequence, we observed that polyunsaturated fatty acids most effectively interfere with binding to hACE2, the receptor for SARS-CoV-2. Using a spike protein pseudo-virus, we also found that linolenic acid and eicosapentaenoic acid significantly block the entry of SARS-CoV-2. In addition, eicosapentaenoic acid showed higher efficacy than linolenic acid in reducing activity of TMPRSS2 and cathepsin L proteases, but neither of the fatty acids affecte...

PLOS ONE, 2021

In the pursuit of suitable and effective solutions to SARS-CoV-2 infection, we investigated the e... more In the pursuit of suitable and effective solutions to SARS-CoV-2 infection, we investigated the efficacy of several phenolic compounds in controlling key cellular mechanisms involved in its infectivity. The way the SARS-CoV-2 virus infects the cell is a complex process and comprises four main stages: attachment to the cognate receptor, cellular entry, replication and cellular egress. Since, this is a multi-part process, it creates many opportunities to develop effective interventions. Targeting binding of the virus to the host receptor in order to prevent its entry has been of particular interest. Here, we provide experimental evidence that, among 56 tested polyphenols, including plant extracts, brazilin, theaflavin-3,3’-digallate, and curcumin displayed the highest binding with the receptor-binding domain of spike protein, inhibiting viral attachment to the human angiotensin-converting enzyme 2 receptor, and thus cellular entry of pseudo-typed SARS-CoV-2 virions. Both, theaflavin-3...

PLOS ONE, 2019

In the search for novel agents against oral pathogens in their planktonic and biofilm form, we ha... more In the search for novel agents against oral pathogens in their planktonic and biofilm form, we have focused our attention on 10-undecynoic acid as the representative of the acetylenic fatty acids. Using macro-broth susceptibility testing method we first established MIC value. Next, the MBC value was determined from a broth dilution minimum inhibitory concentration test by sub-culturing it to BHI agar plates that did not contain the test agent. Anti-biofilm efficacy was tested in 96-well plates coated with saliva using BHI broth supplemented with 1% sucrose as a standard approach. Based on obtained results, MIC value for 10-undecynoic acid was established to be 2.5 mg/ml and the MBC value to be 5 mg/ml. The MBIC 90 showed to be 2.5 mg/ml, however completed inhibition of biofilm formation was achieved at 5.0 mg/ml. MBBC concentration revealed to be the same as MBC value, causing approximately 30% reduction at the same time in biomass of pre-existing biofilm, whereas application of 7.0 mg/ml of 10-undecynoic acid crossed the 50% eradication mark. Strong antiadherent effect was observed upon 10-undecynoic acid application at sub-MBC concentrations as well, complemented with suppression of acidogenicity and aciduricity. Thus, we concluded that 10-undecynoic acid might play an important role in the development of alternative or adjunctive antibacterial and anti-biofilm preventive and/or therapeutic approaches.

Tumori Journal, 2009

Aims and background Lung cancer, a leading cause of cancer death, is associated with exposure to ... more Aims and background Lung cancer, a leading cause of cancer death, is associated with exposure to inhalation carcinogens, most commonly those found in tobacco smoke. We investigated the in vivo effect of dietary supplementation with a nutrient mixture containing lysine, proline, arginine, ascorbic acid, green tea extract, N-acetyl cysteine, selenium, copper and manganese on the development of urethane-induced lung tumors in male A/J mice. Methods After one week of isolation, seven-week-old male A/J mice (n = 25) weighing 17–19 g were randomly divided into three groups: group A (n = 5), group B (n = 10), and group C (n = 10). Mice in groups B and C were each given a single intraperitoneal injection of urethane (1 mg/g body weight) in saline, whereas group A mice received an injection of saline alone. Groups A and B were fed a regular diet, whereas group C was fed the same diet supplemented with 0.5% nutrient mixture. After 20 weeks, mice were sacrificed, lungs were excised and weighed...

American journal of cardiovascular disease, 2016

Heart failure is a multifactorial disease with poor prognosis. There are many hypotheses regardin... more Heart failure is a multifactorial disease with poor prognosis. There are many hypotheses regarding the cause of heart failure. Leading among them are the hemodynamic and the neuro-hormonal hypotheses. Although the energy depletion hypothesis has been fairly recent, there is evidence suggesting that declining bioenergy plays a major role in heart failure. This review explored the myocardial energy depletion hypothesis from the role of micronutrients in correcting and alleviating symptoms of heart failure. Even though focus was on key nutrients such as coenzyme Q10, thiamine, riboflavin, L-carnitine, and taurine, emphasis was on the combined effect of multiple micronutrients as a whole. Search from databases from 2000 to 2015 produced four clinical studies using multiple micronutrients on heart failure. Evidence from the studies show that using high doses of multiple micronutrients may have positive effects on heart failure and simultaneously support the myocardial energy depletion hy...

World Journal of Cardiovascular Diseases, 2016

Atherosclerosis is the precedent to ischemic heart disease, which may lead to angina, myocardial ... more 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.

American journal of cardiovascular disease, 2016

Calcium, sodium and potassium channel blockers are widely prescribed medications for a variety of... more Calcium, sodium and potassium channel blockers are widely prescribed medications for a variety of health problems, most frequently for cardiac arrhythmias, hypertension, angina pectoris and other disorders. However, chronic application of channel blockers is associated with numerous side effects, including worsening cardiac pathology. For example, nifedipine, a calcium-channel blocker was found to be associated with increased mortality and increased risk for myocardial infarction. In addition to the side effects mentioned above by different channel blockers, these drugs can cause arterial wall damage, thereby contributing to vascular wall structure destabilization and promoting events facilitating rupture of plaques. Collagen synthesis is regulated by ascorbic acid, which is also essential for its optimum structure as a cofactor in lysine and proline hydroxylation, a precondition for optimum crosslinking of collagen and elastin. Therefore, the main objective in this study was to eva...

Experimental and Therapeutic Medicine, 2015

American journal of cardiovascular disease, 2015

Lipoprotein(a), a variant of LDL carrying the adhesive glycoprotein apo(a), is a leading risk fac... more Lipoprotein(a), a variant of LDL carrying the adhesive glycoprotein apo(a), is a leading risk factor for cardiovascular disease. Lipoprotein(a) (Lp(a)) is found in humans and subhuman primates but rarely in lower mammals. Better understanding of the evolutionary advantage of this molecule should elucidate its physiological role. We developed a new mouse model with two characteristics of human metabolism: the expression of Lp(a) and the lack of endogenous ascorbate (vitamin C) production. We show that dietary deficiency of ascorbate increases serum levels of Lp(a). Moreover, chronic hypoascorbemia and complete depletion of ascorbate (scurvy) leads to Lp(a) accumulation in the vascular wall and parallels atherosclerotic lesion development. The results suggest that dietary ascorbate deficiency is a risk factor for atherosclerosis independent of dietary lipids. We provide support for the concept that Lp(a) functions as a mobile repair molecule compensating for the structural impairment ...

The Open Natural Products Journal, 2008

Global incidence of tuberculosis, especially multiple-drug resistant tuberculosis, has been incre... more Global incidence of tuberculosis, especially multiple-drug resistant tuberculosis, has been increasing, despite development and use of various antimicrobial drugs for decades, leading to 2 million deaths a year. We evaluated the effect of micronutrient supplementation as an adjunct to standard treatment of patients with active pulmonary tuberculosis, on clinical improvement and frequency of adverse events on 120 patients aged 20 to 65 years diagnosed with active pulmonary tuberculosis at the Kiev Department of Phthisiatry. All participants (Test group) were prescribed standard medication supplemented with vitamin/essential nutrients. A Control group (n=100) of patients recently treated with standard medication alone at this facility were selected by matching to Test patients by stage of disease, confounding conditions, gender, and alcohol consumption. Standard clinical and diagnostic methods were applied to determine baseline values and at the termination of the study. After a two-month period of intensive chemotherapy, cavity healing (primary measure) occurred in 98% of the Test Group, but only in 69% of the Control Group. Furthermore, the Ziehl-Neelson sputum test was negative in 100% of the Test group, but only in 88% of the Control group. Resolution of respiratory compromise was higher in the Test group (87%) than in the Control group (78%). Furthermore, supplementation with vitamin/essential nutrients resulted in a significant decrease in the frequency and severity of adverse events from chemotherapy; only 11% in the Test group experienced adverse events while 46% did so in the Control group. In conclusion, clinical efficacy of chemotherapy was enhanced significantly with adjunctive use of nutrient supplementation. In addition, micronutrient supplementation decreased the frequency and severity of adverse effects from chemotherapy.

Molecular medicine reports

The incidence of type 2 diabetes mellitus is on the increase worldwide, with both environmental a... more The incidence of type 2 diabetes mellitus is on the increase worldwide, with both environmental and genetic factors implicated in its development. Diabetes is often preceded by metabolic syndrome (MS) and may develop in normal adults ingesting a high fructose diet. The effect of high fructose intake on the development of MS in children and adolescents is less clear. Our objective was to study the effects of a nutrient mixture and metformin (MET), a widely used oral diabetic medication, in modulating the physiological and biochemical parameters of a high fructose diet in immature mice. C57BL/6J wild‑type mice aged 7 weeks were administered 12% fructose in their water and MET in distilled water or a diabetic nutrient mix (DNM) over 7 weeks. DNM-fed mice showed a decrease in systolic blood pressure, total cholesterol and fructosamine compared to the fructose-fed only group (p<0.05). A discordant result was observed in the MET group, with a decrease in blood pressure but increases in...