1
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Wang H. Medical Benefits and Polymer Applications of Grapes. Polymers (Basel) 2025; 17:750. [PMID: 40292569 PMCID: PMC11945784 DOI: 10.3390/polym17060750] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2025] [Revised: 03/09/2025] [Accepted: 03/12/2025] [Indexed: 04/30/2025] Open
Abstract
Grapes are a fruit with origins dating back to ancient times. Their first recorded use, as mentioned in the Bible, was in winemaking. The abundance of bioactive compounds in grapes makes them highly valuable. So far, many varieties of cultivated grapes have been developed for table grapes, wine grapes, and raisin production. In addition to these uses, since grapes contain a variety of nutrients, including resveratrol, flavonoids (such as flavonols, anthocyanins, and catechins), melatonin, vitamins, acids, tannins, and other antioxidants, grape extracts have been widely studied for medical applications. This paper reviews the medical effects of these compounds on cancer, cardiovascular disease, brain and neurological disorders, eye diseases, skin disorders, kidney health, diabetes, and gastric diseases, along with the medical applications of grapes in drug delivery, wound dressing, and tissue engineering. In addition, the limitations of the grapes-derived polymers and future research perspectives are discussed. These benefits highlight that the value of grapes extends far beyond their traditional use in wine and raisin production.
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Affiliation(s)
- Hsiuying Wang
- Institute of Statistics, National Yang Ming Chiao Tung University, Hsinchu 300093, Taiwan
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2
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Kelleni MT. Could the next disease X be pandemic of virus-induced encephalitis? what should be our first medical response? Expert Rev Anti Infect Ther 2025; 23:1-3. [PMID: 39560106 DOI: 10.1080/14787210.2024.2432277] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2024] [Revised: 10/25/2024] [Accepted: 11/18/2024] [Indexed: 11/20/2024]
Affiliation(s)
- Mina T Kelleni
- Pharmacology Department, College of Medicine, Minia University, Minya, Egypt
- Research Fellow, INTI International University, Putra Nilai, Malaysia
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3
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Reddy KR, Kumari P, Vinay K, Singh J, Chauhan BS, Kumar P, Srikrishna S, Kumar D, Mishra M, Singaravel M, Prasad NK, Anuraag NS, Sahni C, Sharma S. Safety Study and Compositional Analysis of the Svarnvir-IV Tablet With Special Reference to Its Therapeutic Utility in SARS-CoV-2. Cureus 2024; 16:e75438. [PMID: 39791040 PMCID: PMC11713176 DOI: 10.7759/cureus.75438] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/10/2024] [Indexed: 01/12/2025] Open
Abstract
Aim Traditional Ayurvedic herbo-mineral medicines have proven their potential in managing COVID-19. Cell-based assays of the Svarnvir-IV tablet demonstrated the virucidal activity against SARS-CoV-2 and its therapeutic action, along with safety in cytotoxicity, has been proved. In the present study, in vivo, safety profile and compositional analysis of the Svarnvir-IV tablet were performed. Methods The safety and potency of the Svarnvir tablet were evaluated comprehensively through in vivo drug screening on Drosophila, along with elemental composition analysis of Svarnvir tablets using atomic absorption spectroscopy (AAS), inductively coupled plasma-mass spectroscopy (ICP-MS), X-ray diffraction (XRD), and scanning electron microscopy energy dispersive spectroscopy (SEM-EDS). Results The Svarnvir tablet was found safe in Drosophila and their larvae up to the dosage of 1 mg/ml. In comparison to the control, morphologically and physiologically healthy and active flies were observed without any change in circadian locomotor activity rhythms or activity patterns. In addition, the elemental composition of Svarnvir tablets was evaluated using AAS, ICP-MS, and SEM-EDS, and the microstructure was examined by means of XRD and SEM. Conclusions Overall, these findings will contribute to an accessible and safe therapeutic approach for traditional age-old Ayurvedic medication to combat SARS-CoV-2 variants.
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Affiliation(s)
- K Ramachandra Reddy
- Department of Rasa Shastra (Ayurvedic Pharmaceutics) Faculty of Ayurveda, Institute of Medical Sciences, Banaras Hindu University, Varanasi, IND
| | - Priya Kumari
- Department of Rasa Shastra (Ayurvedic Pharmaceutics) Faculty of Ayurveda, Institute of Medical Sciences, Banaras Hindu University, Varanasi, IND
| | - K Vinay
- College of Medicine, Bharti Vidyapeeth Deemed University (BVDU) Medical College, Sangli, IND
| | - Jyotsna Singh
- Department of Biochemistry, Faculty of Science, Banaras Hindu University, Varanasi, IND
| | - Brijesh S Chauhan
- Department of Zoology, Faculty of Science, Banaras Hindu University, Varanasi, IND
| | - Prabhat Kumar
- Department of Biochemistry, Faculty of Science, Banaras Hindu University, Varanasi, IND
| | - Saripella Srikrishna
- Department of Biochemistry, Faculty of Science, Banaras Hindu University, Varanasi, IND
| | - Deepak Kumar
- Department of Zoology, Faculty of Science, Banaras Hindu University, Varanasi, IND
| | - Madhumita Mishra
- Department of Zoology, Faculty of Science, Banaras Hindu University, Varanasi, IND
| | - Muniyandi Singaravel
- Department of Zoology, Faculty of Science, Banaras Hindu University, Varanasi, IND
| | - N K Prasad
- Department of Metallurgical Engineering, Indian Institute of Technology, Banaras Hindu University, Varanasi, IND
| | - N S Anuraag
- Department of Metallurgical Engineering, Indian Institute of Technology, Banaras Hindu University, Varanasi, IND
| | - Chetan Sahni
- Department of Anatomy, All India Institute of Medical Sciences, Gorakhpur, Gorakhpur, IND
| | - Sanchit Sharma
- School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, IND
- Department of Research and Development, Aimil Pharmaceuticals India Limited, New Delhi, IND
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4
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Kelleni MT. COVID-19 mortality paradox (United States vs Africa): Mass vaccination vs early treatment. World J Exp Med 2024; 14:88674. [PMID: 38590304 PMCID: PMC10999069 DOI: 10.5493/wjem.v14.i1.88674] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2023] [Revised: 12/16/2023] [Accepted: 01/04/2024] [Indexed: 03/19/2024] Open
Abstract
The coronavirus disease 2019 (COVID-19) mortality rate in 55 African countries is almost 4.5 times lower than in the coronavirus disease 2019 (COVID-19) despite Africa having over 4.2 times more people. This mortality paradox is also evident when comparing Nigeria, a heavily populated, poorly vaccinated and weakly mandated country to Israel, a small, highly vaccinated and strictly mandated country. Nigeria has almost 4 times lower COVID mortality than Israel. In this Field of Vision perspective, I explain how this paradox has evolved drawing upon my academic, clinical and social experience. Since April 2020, I've developed and been using the Egyptian immune-modulatory Kelleni's protocol to manage COVID-19 patients including pediatric, geriatric, pregnant, immune-compromised and other individuals suffering from multiple comorbidities. It's unfortunate that severe acute respiratory syndrome coronavirus 2 is still evolving accompanied by more deaths. However in Africa, we've been able to live without anxiety or mandates throughout the pandemic because we trust science and adopted early treatment using safe, and effective repurposed drugs that have saved the majority of COVID-19 patients. This article represents an African and Egyptian tale of honor.
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Affiliation(s)
- Mina Thabet Kelleni
- Department of Pharmacology, College of Medicine, Minia University, Minya 61111, Egypt
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5
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Zheng Y, Li Y, Li M, Wang R, Jiang Y, Zhao M, Lu J, Li R, Li X, Shi S. COVID-19 cooling: Nanostrategies targeting cytokine storm for controlling severe and critical symptoms. Med Res Rev 2024; 44:738-811. [PMID: 37990647 DOI: 10.1002/med.21997] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2022] [Revised: 08/16/2023] [Accepted: 10/29/2023] [Indexed: 11/23/2023]
Abstract
As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants continue to wreak havoc worldwide, the "Cytokine Storm" (CS, also known as the inflammatory storm) or Cytokine Release Syndrome has reemerged in the public consciousness. CS is a significant contributor to the deterioration of infected individuals. Therefore, CS control is of great significance for the treatment of critically ill patients and the reduction of mortality rates. With the occurrence of variants, concerns regarding the efficacy of vaccines and antiviral drugs with a broad spectrum have grown. We should make an effort to modernize treatment strategies to address the challenges posed by mutations. Thus, in addition to the requirement for additional clinical data to monitor the long-term effects of vaccines and broad-spectrum antiviral drugs, we can use CS as an entry point and therapeutic target to alleviate the severity of the disease in patients. To effectively combat the mutation, new technologies for neutralizing or controlling CS must be developed. In recent years, nanotechnology has been widely applied in the biomedical field, opening up a plethora of opportunities for CS. Here, we put forward the view of cytokine storm as a therapeutic target can be used to treat critically ill patients by expounding the relationship between coronavirus disease 2019 (COVID-19) and CS and the mechanisms associated with CS. We pay special attention to the representative strategies of nanomaterials in current neutral and CS research, as well as their potential chemical design and principles. We hope that the nanostrategies described in this review provide attractive treatment options for severe and critical COVID-19 caused by CS.
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Affiliation(s)
- Yu Zheng
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yuke Li
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Mao Li
- Health Management Centre, Clinical Medical College & Affiliated Hospital of Chengdu University, Chengdu University, Chengdu, China
| | - Rujing Wang
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yuhong Jiang
- School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, China
| | - Mengnan Zhao
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Jun Lu
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Rui Li
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Xiaofang Li
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Sanjun Shi
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
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6
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Reddy KR, Sahni C, Sharma S. Antiviral Activity of Svarnvir-IV Tablet Assayed for Activity Against SARS-CoV-2 In Vitro. Cureus 2023; 15:e39421. [PMID: 37362483 PMCID: PMC10288389 DOI: 10.7759/cureus.39421] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/24/2023] [Indexed: 06/28/2023] Open
Abstract
The coronavirus disease (COVID-19), caused by the virus SARS-CoV-2, has become a global pandemic in a very short time span. While several vaccines have been developed in the last year, specific treatments for CoV infection are still being explored. Thus, the situation highlights the need to develop safe and efficacious antiviral therapeutics. Ayurvedic Rasayana therapy has been traditionally used in India for its holistic healing systems and proven history of empirical use. There is emerging evidence that Ayurvedic treatment methodologies and herbal medicines may be effective strategies in combating COVID-19. The present study is aimed at evaluating the antiviral and therapeutic activity of an Ayurvedic herbomineral formulation (Svarnvir-IV tablet, 450 mg) against the SARS-CoV-2 virus in vitro. A cell-based assay was conducted to evaluate the cytotoxicity of the Svarnvir-IV tablets (Aimil Pharmaceuticals, Delhi, India) for the determination of virucidal activity assessment (at 2 hours) and therapeutic activity assessment (at 1 hour, 2 hours, and 4 hours). When incubated with SARS-CoV-2 virus at 0.1 multiplicity of infection (MoI) for two hours, Svarnvir-IV tablet exhibited virucidal activity against SARS-CoV-2 with an EC50 value of 0.0058 mg/ml. It also exhibited therapeutic activity when treated with cells infected with the SARS-CoV-2 virus (0.1 MoI) for 1 hour, 2 hours and 4 hours post-infection, with an EC50 value of 0.094 mg/ml, 0.023 mg/ml, and 0.05 mg/ml, respectively. The original supporting data obtained from this study, along with existing Ayurvedic traditional information, has shown encouraging results.
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Affiliation(s)
- K Ramachandra Reddy
- Department of Rasa Shastra, Faculty of Ayurveda, Institute of Medical Sciences, Banaras Hindu University, Varanasi, IND
| | - Chetan Sahni
- Department of Anatomy, Institute of Medical Sciences, Banaras Hindu University, Varanasi, IND
| | - Sanchit Sharma
- Research and Development, Aimil Pharmaceuticals, Delhi, IND
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7
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Catenacci L, Vicatos AI, Sorrenti M, Edmonds-Smith C, Bonferoni MC, Caira MR. Complexation between the Antioxidant Pterostilbene and Derivatized Cyclodextrins in the Solid State and in Aqueous Solution. Pharmaceuticals (Basel) 2023; 16:247. [PMID: 37259394 PMCID: PMC9966925 DOI: 10.3390/ph16020247] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2023] [Revised: 02/01/2023] [Accepted: 02/03/2023] [Indexed: 10/26/2024] Open
Abstract
Inadequate aqueous solubilities of bioactive compounds hinder their ability to be developed for medicinal applications. The potent antioxidant pterostilbene (PTB) is a case in point. The aim of this study was to use a series of modified water-soluble cyclodextrins (CDs), namely, hydroxypropyl β-CD (HPβCD), dimethylated β-CD (DIMEB), randomly methylated β-CD (RAMEB), and sulfobutyl ether β-CD sodium salt (SBECD) to prepare inclusion complexes of PTB via various solid, semi-solid, and solution-based treatments. Putative CD-PTB products generated by solid-state co-grinding, kneading, irradiation with microwaves, and the evaporative treatment of CD-PTB solutions were considered to have potential for future applications. Primary analytical methods for examining CD-PTB products included differential scanning calorimetry and Fourier transform infrared spectroscopy to detect the occurrence of binary complex formation. Phase solubility analysis was used to probe CD-PTB complexation in an aqueous solution. Complexation was evident in both the solid-state and in solution. Complex association constants (K1:1) in an aqueous solution spanned the approximate range of 15,000 to 55,000 M-1; the values increased with the CDs in the order HPβCD < DIMEB < RAMEB < SBECD. Significant PTB solubility enhancement factors were recorded at 100 mM CD concentrations, the most accurately determined values being in the range 700-fold to 1250-fold.
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Affiliation(s)
- Laura Catenacci
- Department of Drug Sciences, University of Pavia, Viale Taramelli 12, 27100 Pavia, Italy
| | - Alexios I. Vicatos
- Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa
| | - Milena Sorrenti
- Department of Drug Sciences, University of Pavia, Viale Taramelli 12, 27100 Pavia, Italy
| | | | | | - Mino R. Caira
- Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa
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8
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Preliminary In Vivo Evidence of Oral Selenium Supplementation as a Potentiating Agent on a Vector-Based COVID-19 Vaccine in BALB/c Mice. Vaccines (Basel) 2022; 11:vaccines11010057. [PMID: 36679902 PMCID: PMC9863471 DOI: 10.3390/vaccines11010057] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2022] [Revised: 12/21/2022] [Accepted: 12/22/2022] [Indexed: 12/28/2022] Open
Abstract
Evidence of efficacy and toxicity of oral selenium supplementation in vaccine administration against severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) in mice models is scarce. In this study, 4 × 109 virus particles (40 µL) dose of Janssen COVID-19 intramuscular injection vaccine was supplemented with a commercial selenium supplement and sodium selenite orally in BALB/c mice (N = 18). Qualitative determination of anti-spike IgG antibody response using indirect Enzyme-Linked Immunosorbent Assay (ELISA) showed significant (p ≤ 0.001) increase in anti-spike IgG antibody response for mice groups immunized with vaccine and supplemented selenium. Furthermore, cytokine profiling using real-time quantitative polymerase chain reaction also showed an increase in IL-6 and IL-10 mRNA levels normalized using hypoxanthine phosphoribosyl transferase 1 (Hprt1) and glyceraldehyde 3-phosphate dehydrogenase (Gadph) housekeeping genes. There was no statistical significance (p < 0.465) among treated and untreated groups for alanine transaminase (ALT), aspartate transaminase (AST), urea, and creatinine parameters. The study presents preliminary findings and suggests that supplementing Janssen COVID-19 vaccines with selenium can generate more robust immune responses.
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9
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Afzal O, Altamimi ASA, Nadeem MS, Alzarea SI, Almalki WH, Tariq A, Mubeen B, Murtaza BN, Iftikhar S, Riaz N, Kazmi I. Nanoparticles in Drug Delivery: From History to Therapeutic Applications. NANOMATERIALS (BASEL, SWITZERLAND) 2022; 12:4494. [PMID: 36558344 PMCID: PMC9781272 DOI: 10.3390/nano12244494] [Citation(s) in RCA: 125] [Impact Index Per Article: 41.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/11/2022] [Revised: 12/04/2022] [Accepted: 12/14/2022] [Indexed: 05/25/2023]
Abstract
Current research into the role of engineered nanoparticles in drug delivery systems (DDSs) for medical purposes has developed numerous fascinating nanocarriers. This paper reviews the various conventionally used and current used carriage system to deliver drugs. Due to numerous drawbacks of conventional DDSs, nanocarriers have gained immense interest. Nanocarriers like polymeric nanoparticles, mesoporous nanoparticles, nanomaterials, carbon nanotubes, dendrimers, liposomes, metallic nanoparticles, nanomedicine, and engineered nanomaterials are used as carriage systems for targeted delivery at specific sites of affected areas in the body. Nanomedicine has rapidly grown to treat certain diseases like brain cancer, lung cancer, breast cancer, cardiovascular diseases, and many others. These nanomedicines can improve drug bioavailability and drug absorption time, reduce release time, eliminate drug aggregation, and enhance drug solubility in the blood. Nanomedicine has introduced a new era for drug carriage by refining the therapeutic directories of the energetic pharmaceutical elements engineered within nanoparticles. In this context, the vital information on engineered nanoparticles was reviewed and conferred towards the role in drug carriage systems to treat many ailments. All these nanocarriers were tested in vitro and in vivo. In the coming years, nanomedicines can improve human health more effectively by adding more advanced techniques into the drug delivery system.
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Affiliation(s)
- Obaid Afzal
- Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al Kharj 11942, Saudi Arabia
| | - Abdulmalik S A Altamimi
- Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al Kharj 11942, Saudi Arabia
| | - Muhammad Shahid Nadeem
- Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia
| | - Sami I Alzarea
- Department of Pharmacology, College of Pharmacy, Jouf University, Sakaka 72341, Saudi Arabia
| | - Waleed Hassan Almalki
- Department of Pharmacology, College of Pharmacy, Umm Al-Qura University, Makkah 21955, Saudi Arabia
| | - Aqsa Tariq
- Institute of Molecular Biology and Biotechnology (IMBB), The University of Lahore, Lahore 54000, Pakistan
| | - Bismillah Mubeen
- Institute of Molecular Biology and Biotechnology (IMBB), The University of Lahore, Lahore 54000, Pakistan
| | - Bibi Nazia Murtaza
- Department of Zoology, Abbottabad University of Science and Technology (AUST), Abbottabad 22310, Pakistan
| | - Saima Iftikhar
- School of Biological Sciences, University of Punjab, Lahore 54000, Pakistan
| | - Naeem Riaz
- Department of Pharmacy, COMSATS University, Abbottabad 22020, Pakistan
| | - Imran Kazmi
- Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia
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10
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Pisoschi AM, Iordache F, Stanca L, Gajaila I, Ghimpeteanu OM, Geicu OI, Bilteanu L, Serban AI. Antioxidant, Anti-inflammatory, and Immunomodulatory Roles of Nonvitamin Antioxidants in Anti-SARS-CoV-2 Therapy. J Med Chem 2022; 65:12562-12593. [PMID: 36136726 PMCID: PMC9514372 DOI: 10.1021/acs.jmedchem.2c01134] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Indexed: 11/28/2022]
Abstract
Viral pathologies encompass activation of pro-oxidative pathways and inflammatory burst. Alleviating overproduction of reactive oxygen species and cytokine storm in COVID-19 is essential to counteract the immunogenic damage in endothelium and alveolar membranes. Antioxidants alleviate oxidative stress, cytokine storm, hyperinflammation, and diminish the risk of organ failure. Direct antiviral roles imply: impact on viral spike protein, interference with the ACE2 receptor, inhibition of dipeptidyl peptidase 4, transmembrane protease serine 2 or furin, and impact on of helicase, papain-like protease, 3-chyomotrypsin like protease, and RNA-dependent RNA polymerase. Prooxidative environment favors conformational changes in the receptor binding domain, promoting the affinity of the spike protein for the host receptor. Viral pathologies imply a vicious cycle, oxidative stress promoting inflammatory responses, and vice versa. The same was noticed with respect to the relationship antioxidant impairment-viral replication. Timing, dosage, pro-oxidative activities, mutual influences, and interference with other antioxidants should be carefully regarded. Deficiency is linked to illness severity.
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Affiliation(s)
- Aurelia Magdalena Pisoschi
- Faculty of Veterinary Medicine, Department Preclinical
Sciences, University of Agronomic Sciences and Veterinary Medicine of
Bucharest, 105 Splaiul Independentei, 050097Bucharest,
Romania
| | - Florin Iordache
- Faculty of Veterinary Medicine, Department Preclinical
Sciences, University of Agronomic Sciences and Veterinary Medicine of
Bucharest, 105 Splaiul Independentei, 050097Bucharest,
Romania
| | - Loredana Stanca
- Faculty of Veterinary Medicine, Department Preclinical
Sciences, University of Agronomic Sciences and Veterinary Medicine of
Bucharest, 105 Splaiul Independentei, 050097Bucharest,
Romania
| | - Iuliana Gajaila
- Faculty of Veterinary Medicine, Department Preclinical
Sciences, University of Agronomic Sciences and Veterinary Medicine of
Bucharest, 105 Splaiul Independentei, 050097Bucharest,
Romania
| | - Oana Margarita Ghimpeteanu
- Faculty of Veterinary Medicine, Department Preclinical
Sciences, University of Agronomic Sciences and Veterinary Medicine of
Bucharest, 105 Splaiul Independentei, 050097Bucharest,
Romania
| | - Ovidiu Ionut Geicu
- Faculty of Veterinary Medicine, Department Preclinical
Sciences, University of Agronomic Sciences and Veterinary Medicine of
Bucharest, 105 Splaiul Independentei, 050097Bucharest,
Romania
- Faculty of Biology, Department Biochemistry and
Molecular Biology, University of Bucharest, 91-95 Splaiul
Independentei, 050095Bucharest, Romania
| | - Liviu Bilteanu
- Faculty of Veterinary Medicine, Department Preclinical
Sciences, University of Agronomic Sciences and Veterinary Medicine of
Bucharest, 105 Splaiul Independentei, 050097Bucharest,
Romania
- Molecular Nanotechnology Laboratory,
National Institute for Research and Development in
Microtechnologies, 126A Erou Iancu Nicolae Street, 077190Bucharest,
Romania
| | - Andreea Iren Serban
- Faculty of Veterinary Medicine, Department Preclinical
Sciences, University of Agronomic Sciences and Veterinary Medicine of
Bucharest, 105 Splaiul Independentei, 050097Bucharest,
Romania
- Faculty of Biology, Department Biochemistry and
Molecular Biology, University of Bucharest, 91-95 Splaiul
Independentei, 050095Bucharest, Romania
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11
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New Insights into Dietary Pterostilbene: Sources, Metabolism, and Health Promotion Effects. Molecules 2022; 27:molecules27196316. [PMID: 36234852 PMCID: PMC9571692 DOI: 10.3390/molecules27196316] [Citation(s) in RCA: 44] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2022] [Revised: 09/17/2022] [Accepted: 09/21/2022] [Indexed: 11/17/2022] Open
Abstract
Pterostilbene (PTS), a compound most abundantly found in blueberries, is a natural analog of resveratrol. Several plant species, such as peanuts and grapes, produce PTS. While resveratrol has been extensively studied for its antioxidant properties, recent evidence also points out the diverse therapeutic potential of PTS. Several studies have identified the robust pharmacodynamic features of PTS, including better intestinal absorption and elevated hepatic stability than resveratrol. Indeed, due to its higher bioavailability paired with reduced toxicity compared to other stilbenes, PTS has become an attractive drug candidate for the treatment of several disease conditions, including diabetes, cancer, cardiovascular disease, neurodegenerative disorders, and aging. This review article provides an extensive summary of the nutraceutical potential of PTS in various disease conditions while discussing the crucial mechanistic pathways implicated. In particular, we share insights from our studies about the Nrf2-mediated effect of PTS in diabetes and associated complications. Moreover, we elucidate the important sources of PTS and discuss in detail its pharmacokinetics and the range of formulations and routes of administration used across experimental studies and human clinical trials. Furthermore, this review also summarizes the strategies successfully used to improve dietary availability and the bio-accessibility of PTS.
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Catalano A, Iacopetta D, Ceramella J, Maio ACD, Basile G, Giuzio F, Bonomo MG, Aquaro S, Walsh TJ, Sinicropi MS, Saturnino C, Geronikaki A, Salzano G. Are Nutraceuticals Effective in COVID-19 and Post-COVID Prevention and Treatment? Foods 2022; 11:2884. [PMID: 36141012 PMCID: PMC9498392 DOI: 10.3390/foods11182884] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2022] [Revised: 09/09/2022] [Accepted: 09/15/2022] [Indexed: 11/17/2022] Open
Abstract
The beginning of the end or the end of the beginning? After two years mastered by coronavirus disease 19 (COVID-19) pandemic, we are now witnessing a turnaround. The reduction of severe cases and deaths from COVID-19 led to increasing importance of a new disease called post-COVID syndrome. The term post-COVID is used to indicate permanency of symptoms in patients who have recovered from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Immune, antiviral, antimicrobial therapies, as well as ozone therapy have been used to treat COVID-19 disease. Vaccines have then become available and administered worldwide to prevent the insurgence of the disease. However, the pandemic is not over yet at all given the emergence of new omicron variants. New therapeutic strategies are urgently needed. In this view, great interest was found in nutraceutical products, including vitamins (C, D, and E), minerals (zinc), melatonin, probiotics, flavonoids (quercetin), and curcumin. This review summarizes the role of nutraceuticals in the prevention and/or treatment of COVID-19 disease and post-COVID syndrome.
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Affiliation(s)
- Alessia Catalano
- Department of Pharmacy-Drug Sciences, University of Bari “Aldo Moro”, 70126 Bari, Italy
| | - Domenico Iacopetta
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Arcavacata di Rende, Italy
| | - Jessica Ceramella
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Arcavacata di Rende, Italy
| | - Azzurra Chiara De Maio
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Arcavacata di Rende, Italy
| | - Giovanna Basile
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Arcavacata di Rende, Italy
| | - Federica Giuzio
- Department of Science, University of Basilicata, 85100 Potenza, Italy
| | | | - Stefano Aquaro
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Arcavacata di Rende, Italy
| | - Thomas J. Walsh
- Center for Innovative Therapeutics and Diagnostics, Richmond, VA 23223, USA
| | - Maria Stefania Sinicropi
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Arcavacata di Rende, Italy
| | - Carmela Saturnino
- Department of Science, University of Basilicata, 85100 Potenza, Italy
| | - Athina Geronikaki
- School of Pharmacy, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
| | - Giovanni Salzano
- Department of Science, University of Basilicata, 85100 Potenza, Italy
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13
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Brahmi F, Vejux A, Ghzaiel I, Ksila M, Zarrouk A, Ghrairi T, Essadek S, Mandard S, Leoni V, Poli G, Vervandier-Fasseur D, Kharoubi O, El Midaoui A, Atanasov AG, Meziane S, Latruffe N, Nasser B, Bouhaouala-Zahar B, Masmoudi-Kouki O, Madani K, Boulekbache-Makhlouf L, Lizard G. Role of Diet and Nutrients in SARS-CoV-2 Infection: Incidence on Oxidative Stress, Inflammatory Status and Viral Production. Nutrients 2022; 14:2194. [PMID: 35683996 PMCID: PMC9182601 DOI: 10.3390/nu14112194] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2022] [Revised: 05/10/2022] [Accepted: 05/17/2022] [Indexed: 11/17/2022] Open
Abstract
Coronavirus illness (COVID-19) is an infectious pathology generated by intense severe respiratory syndrome coronavirus 2 (SARS-CoV-2). This infectious disease has emerged in 2019. The COVID-19-associated pandemic has considerably affected the way of life and the economy in the world. It is consequently crucial to find solutions allowing remedying or alleviating the effects of this infectious disease. Natural products have been in perpetual application from immemorial time given that they are attested to be efficient towards several illnesses without major side effects. Various studies have shown that plant extracts or purified molecules have a promising inhibiting impact towards coronavirus. In addition, it is substantial to understand the characteristics, susceptibility and impact of diet on patients infected with COVID-19. In this review, we recapitulate the influence of extracts or pure molecules from medicinal plants on COVID-19. We approach the possibilities of plant treatment/co-treatment and feeding applied to COVID-19. We also show coronavirus susceptibility and complications associated with nutrient deficiencies and then discuss the major food groups efficient on COVID-19 pathogenesis. Then, we covered emerging technologies using plant-based SARS-CoV-2 vaccine. We conclude by giving nutrient and plants curative therapy recommendations which are of potential interest in the COVID-19 infection and could pave the way for pharmacological treatments or co-treatments of COVID-19.
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Affiliation(s)
- Fatiha Brahmi
- Laboratory Biomathématique, Biochimie, Biophysique et Scientométrie, Faculté des Sciences de la Nature et de la Vie, Université de Bejaia, Bejaia 06000, Algeria; (K.M.); (L.B.-M.)
| | - Anne Vejux
- Department of Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism, University of Bourgogne Franche-Comte, 21000 Dijon, France; (A.V.); (I.G.); (M.K.); (S.E.); (N.L.)
| | - Imen Ghzaiel
- Department of Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism, University of Bourgogne Franche-Comte, 21000 Dijon, France; (A.V.); (I.G.); (M.K.); (S.E.); (N.L.)
- Lab-NAFS ‘Nutrition-Functional Food & Vascular Health’, Faculty of Medicine, LR12ES05, University Monastir, Monastir 5000, Tunisia;
| | - Mohamed Ksila
- Department of Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism, University of Bourgogne Franche-Comte, 21000 Dijon, France; (A.V.); (I.G.); (M.K.); (S.E.); (N.L.)
- Laboratory of Neurophysiology, Cellular Physiopathology and Valorisation of Biomolecules, (LR18ES03), Department of Biology, Faculty of Sciences, University Tunis El Manar, Tunis 2092, Tunisia; (T.G.); (O.M.-K.)
| | - Amira Zarrouk
- Lab-NAFS ‘Nutrition-Functional Food & Vascular Health’, Faculty of Medicine, LR12ES05, University Monastir, Monastir 5000, Tunisia;
- Laboratory of Biochemistry, Faculty of Medicine, University of Sousse, Sousse 4000, Tunisia
| | - Taoufik Ghrairi
- Laboratory of Neurophysiology, Cellular Physiopathology and Valorisation of Biomolecules, (LR18ES03), Department of Biology, Faculty of Sciences, University Tunis El Manar, Tunis 2092, Tunisia; (T.G.); (O.M.-K.)
| | - Soukena Essadek
- Department of Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism, University of Bourgogne Franche-Comte, 21000 Dijon, France; (A.V.); (I.G.); (M.K.); (S.E.); (N.L.)
- Laboratory Neuroscience and Biochemistry, University of Hassan 1st, Settat 26000, Morocco;
| | - Stéphane Mandard
- Lipness Team and LipSTIC LabEx, UFR Sciences de Santé, INSERM/University of Bourgogne Franche-Comté LNC UMR1231, 21000 Dijon, France;
| | - Valerio Leoni
- Department of Laboratory Medicine, University of Milano-Bicocca, Azienda Socio Sanitaria Territoriale Brianza ASST-Brianza, Desio Hospital, Via Mazzini 1, 20833 Desio, Italy;
| | - Giuseppe Poli
- Department of Clinical and Biological Sciences, San Luigi Hospital, University of Turin, 10043 Orbassano (Turin), Italy;
| | - Dominique Vervandier-Fasseur
- Team OCS, Institute of Molecular Chemistry of University of Burgundy (ICMUB UMR CNRS 6302), University of Bourgogne Franche-Comté, 21000 Dijon, France;
| | - Omar Kharoubi
- Laboratory of Experimental Biotoxicology, Biodepollution and Phytoremediation, Faculty of Life and Natural Sciences, University Oran 1 ABB, Oran 31000, Algeria;
| | - Adil El Midaoui
- Department of Pharmacology and Physiology, Faculty of Medicine, University of Montreal, Montreal, QC H3C 3J7, Canada;
- Faculty of Sciences and Techniques, Moulay Ismail University of Meknes, Errachidia 52000, Morocco
| | - Atanas G. Atanasov
- Institute of Genetics and Animal Breeding of the Polish Academy of Sciences, Jastrzebiec, 05-552 Magdalenka, Poland;
| | - Smail Meziane
- Institut Européen des Antioxydants, 1b Rue Victor de Lespinats, 54230 Neuves-Maison, France;
| | - Norbert Latruffe
- Department of Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism, University of Bourgogne Franche-Comte, 21000 Dijon, France; (A.V.); (I.G.); (M.K.); (S.E.); (N.L.)
| | - Boubker Nasser
- Laboratory Neuroscience and Biochemistry, University of Hassan 1st, Settat 26000, Morocco;
| | - Balkiss Bouhaouala-Zahar
- Laboratory of Biomolecules, Venoms and Theranostic Applications, Pasteur Institute of Tunis, University of Tunis El Manar, Tunis 1002, Tunisia;
| | - Olfa Masmoudi-Kouki
- Laboratory of Neurophysiology, Cellular Physiopathology and Valorisation of Biomolecules, (LR18ES03), Department of Biology, Faculty of Sciences, University Tunis El Manar, Tunis 2092, Tunisia; (T.G.); (O.M.-K.)
| | - Khodir Madani
- Laboratory Biomathématique, Biochimie, Biophysique et Scientométrie, Faculté des Sciences de la Nature et de la Vie, Université de Bejaia, Bejaia 06000, Algeria; (K.M.); (L.B.-M.)
- Centre de Recherche en Technologie des Industries Agroalimentaires, Route de Targua Ouzemour, Bejaia 06000, Algeria
| | - Lila Boulekbache-Makhlouf
- Laboratory Biomathématique, Biochimie, Biophysique et Scientométrie, Faculté des Sciences de la Nature et de la Vie, Université de Bejaia, Bejaia 06000, Algeria; (K.M.); (L.B.-M.)
| | - Gérard Lizard
- Department of Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism, University of Bourgogne Franche-Comte, 21000 Dijon, France; (A.V.); (I.G.); (M.K.); (S.E.); (N.L.)
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14
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van Brummelen R, van Brummelen AC. The potential role of resveratrol as supportive antiviral in treating conditions such as COVID-19 - A formulator's perspective. Biomed Pharmacother 2022; 148:112767. [PMID: 35240527 PMCID: PMC8884665 DOI: 10.1016/j.biopha.2022.112767] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2022] [Revised: 02/21/2022] [Accepted: 02/27/2022] [Indexed: 11/18/2022] Open
Abstract
With an increased transmissibility but milder form of disease of the omicron variant of COVID-19 and the newer antivirals often still out of reach of many populations, a refocus of the current treatment regimens is required. Safe, affordable, and available adjuvant treatments should also be considered and known drugs and substances need to be repurposed and tested. Resveratrol, a well-known antioxidant of natural origin, shown to act as an antiviral as well as playing a role in immune stimulation, down regulation of the pro-inflammatory cytokine release and reducing lung injury by reducing oxidative stress, is such an option. New initiatives and collaborations will however need to be found to unleash resveratrol's full potential in the pharmaceutical market.
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15
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Kelleni MT. NSAIDs and Kelleni's protocol as potential early COVID-19 treatment game changer: could it be the final countdown? Inflammopharmacology 2022; 30:343-348. [PMID: 34822026 PMCID: PMC8613510 DOI: 10.1007/s10787-021-00896-7] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2021] [Accepted: 11/14/2021] [Indexed: 12/12/2022]
Abstract
We have previously published several papers illustrating numerous immunomodulatory and anti-inflammatory potential benefits when we repurposed safe, generic non-steroidal anti-inflammatory drugs (NSAIDs)/nitazoxanide/azithromycin (Kelleni's protocol), to early manage our COVID-19 pediatric, adult, and pregnant patients. In this manuscript, we discuss some recently published meta-analysis and clinical studies supporting our practice and discuss a molecular study that might be interpreted as an academic proof that our protocol might also prevent SARS-CoV-2 replication. Moreover, after aspirin has been suggested to be independently associated with reduced risk of mechanical ventilation, ICU admission and in-hospital mortality of COVID-19, we claim that the molecular interpretation of the results that led to this suggestion was not scientifically accurate, and we provide our academic interpretation confirming that low-dose aspirin is least likely to improve COVID-19 mortality through anticoagulation as was suggested. Furthermore, we describe other potential benefits related to aspirin-triggered lipoxins and resolvins while illustrating how NSAIDs interfere with COX-1, COX-2, SARS-CoV-2/ SARS-CoV-2 ORF protein-dependent activation of caspases and their subsequent mitochondrial dysfunction, endoplasmic reticulum stress, apoptosis and necroptosis which were associated with COVID-19 complications. Similarly, NSAIDs are known caspase inhibitors and thus they might independently inhibit other caspase-related COVID-19-associated downstream pathological signaling mechanisms. Finally, we postulated that CARD-14, a caspase recruitment domain-containing protein, polymorphisms might play a role in the development of severe and critical COVID-19 and confirmed our old call to early adopt NSAIDs, as an integral part of Kelleni's protocol, as of choice in its management aiming to end this pandemic.
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Affiliation(s)
- Mina T Kelleni
- Pharmacology Department, College of Medicine, Minia University, Minya, Egypt.
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16
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Ni YQ, Zeng HH, Song XW, Zheng J, Wu HQ, Liu CT, Zhang Y. Potential metal-related strategies for prevention and treatment of COVID-19. RARE METALS 2022; 41:1129-1141. [PMID: 35068851 PMCID: PMC8761834 DOI: 10.1007/s12598-021-01894-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Revised: 09/28/2021] [Accepted: 10/10/2021] [Indexed: 05/07/2023]
Abstract
Abstract The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed severe threats to human health, public safety, and the global economy. Metal nutrient elements can directly or indirectly take part in human immune responses, and metal-related drugs have served as antiviral drugs and/or enzyme inhibitors for many years, providing potential solutions to the prevention and treatment of COVID-19. Metal-based drugs are currently under a variety of chemical structures and exhibit wide-range bioactivities, demonstrating irreplaceable advantages in pharmacology. This review is an intention to summarize recent progress in the prevention and treatment strategies against COVID-19 from the perspective of metal pharmacology. The current and potential utilization of metal-based drugs is briefly introduced. Specifically, metallohydrogels that have been shown to present superior antiviral activities are stressed in the paper as potential drugs for the treatment of COVID-19. Graphic abstract
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Affiliation(s)
- Ya-Qiong Ni
- Hunan Provincial Key Laboratory of Micro and Nano Materials Interface Science, College of Chemistry and Chemical Engineering, Central South University, Changsha, 410083 China
| | - Hui-Hui Zeng
- Hunan Provincial Key Laboratory of Micro and Nano Materials Interface Science, College of Chemistry and Chemical Engineering, Central South University, Changsha, 410083 China
| | - Xian-Wen Song
- Hunan Provincial Key Laboratory of Micro and Nano Materials Interface Science, College of Chemistry and Chemical Engineering, Central South University, Changsha, 410083 China
| | - Jun Zheng
- Hunan Provincial Key Laboratory of Micro and Nano Materials Interface Science, College of Chemistry and Chemical Engineering, Central South University, Changsha, 410083 China
| | - Hui-Qiong Wu
- Hanshan Normal University, Chaozhou, 521041 China
- College of Chemistry and Environmental Engineering, Shenzhen University, Shenzhen, 518071 China
| | - Chun-Tai Liu
- Key Laboratory of Materials Processing and Mold (Zhengzhou University), Ministry of Education, Zhengzhou, 450002 China
| | - Yi Zhang
- Hunan Provincial Key Laboratory of Micro and Nano Materials Interface Science, College of Chemistry and Chemical Engineering, Central South University, Changsha, 410083 China
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17
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A Brief Updated Review of Advances to Enhance Resveratrol's Bioavailability. Molecules 2021; 26:molecules26144367. [PMID: 34299642 PMCID: PMC8305180 DOI: 10.3390/molecules26144367] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Revised: 07/02/2021] [Accepted: 07/07/2021] [Indexed: 11/17/2022] Open
Abstract
Resveratrol (RES) has a low bioavailability. This limitation was addressed in an earlier review and several recommendations were offered. A literature search was conducted in order to determine the extent of the research that was conducted in line with these recommendations, along with new developments in this field. Most of the identified studies were pre-clinical and confirmed the heightened activity of RES analogues compared to their parent compound. Although this has provided additional scientific kudos for these compounds and has strengthened their potential to be developed into phytopharmaceutical products, clinical trials designed to confirm this increased activity remain lacking and are warranted.
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18
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Mu Q, Najafi M. Resveratrol for targeting the tumor microenvironment and its interactions with cancer cells. Int Immunopharmacol 2021; 98:107895. [PMID: 34171623 DOI: 10.1016/j.intimp.2021.107895] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Revised: 06/09/2021] [Accepted: 06/13/2021] [Indexed: 12/17/2022]
Abstract
Tumor resistance to therapy modalities is one of the major challenges to the eradication of cancer cells and complete treatment. Tumor includes a wide range of cancer and non-cancer cells that play key roles in the proliferation of cancer cells and suppression of anti-tumor immunity. For overcoming tumor resistance to therapy, it is important to have in-depth knowledge relating to intercellular communications within the tumor microenvironment (TME). TME includes various types of immune cells such as CD4 + T lymphocytes, cytotoxic T lymphocytes (CTLs), natural killer (NK) cells, macrophages, and T regulatory cells (Tregs). Furthermore, some non-immune cells like cancer stem cells (CSCs), mesenchymal stem cells (MSCs), and cancer-associated fibroblasts (CAFs) are involved in the promotion of tumor growth. The interactions between these cells with cancer cells play a key role in tumor growth or inhibition. Resveratrol as a natural agent has shown the ability to modulate the immune system to potentiate anti-tumor immunity and also help to attenuate cancer cells and CSCs resistance. Thus, this review explains how resveratrol can modulate interactions within TME.
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Affiliation(s)
- Qi Mu
- College of Nursing, Inner Mongolia University for Nationalities, Tongliao 028000, China.
| | - Masoud Najafi
- Medical Technology Research Center, Institute of Health Technology, Kermanshah University of Medical Sciences, Kermanshah, Iran.
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