Publications by authors named "Shaker A Mousa"

380 Publications

Oral Contraceptive Types in Relation to ABO Blood Groups Among Saudi Women of Different Reproductive Age Groups and Impact on Venous Thromboembolism.

Clin Appl Thromb Hemost 2020 Jan-Dec;26:1076029620966051

Synapse Research Institute, Maastricht, the Netherlands.

Saudi women have recently started using oral contraceptives (OCs), which has led to risk of venous thromboembolism (VTE). The risk varies with the type of OC generations used, and with OC use the risk for VTE increases by 2- to 6-fold. This study evaluated the effect of OC types in relation to ABO blood group on the risk of VTE among Saudi women. Thrombin generation (TG) was measured in the plasma of the women in the presence and absence of platelet rich plasma, platelet poor plasma and thrombomodulin or activated protein C. OC usage increased TG parameters ETP and Peak height by 9.81% and 16.04%, respectively. An increased risk of VTE was seen among women on third generation OCs as compared to those on second generation products. Within OC generations, we found that for women using fourth generation OCs, their ETP increased by 36.18% as compared to those using second generation and by 6.07% in those using third generation compared to those using second generation. There was significant difference with respect to ABO blood groups and OC generation types, but larger sample size is required. Women who are 40 years and older and using third generation OC had a higher risk of having thrombosis (11.84%), as compared to those using second generation OC (8.79%) and to those using fourth generation OC (5.03%). An association between different OC groups and non-O blood group in thrombosis generation was noted. TG parameters were significantly increased in relation to BMI when comparing to OC users versus non-users. In addition, inhibition of TG parameters in the presence of recombinant human thrombomodulin (TM) and activated protein C (APC) were significantly increased.
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http://dx.doi.org/10.1177/1076029620966051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7607804PMC
July 2021

Transcriptomic and biochemical effects of pycnogenol in ameliorating heat stress-related oxidative alterations in rats.

J Therm Biol 2020 Oct 21;93:102683. Epub 2020 Aug 21.

Department of Biochemistry, Faculty of Veterinary Medicine, Damanhour University, Damanhour, 22511, Egypt. Electronic address:

Background: Heat stress is a condition that is due to extreme heat exposure. It occurs when the body cannot keep its temperature healthy in response to a hot climate and associated with oxidative stress. Testicular hyperthermia can induce apoptosis of sperm cells, affect sperm production and decrease sperm concentration, leading to sperm disorder, for this reason, we examined the protective impact of pycnogenol that it has a wide range of biological benefits, including antioxidant, anti-inflammatory and anti-cancer activities against the oxidative alterations that happen in testicular and brain tissues due to heat stress in rats.

Study Design: Forty-eight Wistar male rats, approximately around 6 weeks age were allocated randomly into four groups (12 in each) of control, HS (subjected to heat stress and supplemented orally with 50 mg of pycnogenol/kg b. w./day dissolved in saline for 21 days), and pycnogenol (rats supplemented orally with 50 mg of pycnogenol/kg b. w./day dissolved in saline for 21 days).

Results: Data revealed a promising role of pycnogenol as an antioxidant, natural product to successfully reverse the heat-induced oxidative alterations in testicular and brain tissues of rats through significant upregulation of superoxide dismutase-2, catalase, reduced glutathione, and anti-apoptotic gene, while downregulating pro-apoptotic, and heat shock protein70. Pycnogenol treatment also reversed the reproductive hormone level and spermatogenesis to their normal values.

Conclusion: Pycnogenol as a natural protective supplement could recover these heat stress-induced oxidative changes in testes and hypothalamus.
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http://dx.doi.org/10.1016/j.jtherbio.2020.102683DOI Listing
October 2020

Emerging Nanopharmaceuticals and Nanonutraceuticals in Cancer Management.

Biomedicines 2020 Sep 12;8(9). Epub 2020 Sep 12.

The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY 12144, USA.

Nanotechnology is the science of nanoscale, which is the scale of nanometers or one billionth of a meter. Nanotechnology encompasses a broad range of technologies, materials, and manufacturing processes that are used to design and/or enhance many products, including medicinal products. This technology has achieved considerable progress in the oncology field in recent years. Most chemotherapeutic agents are not specific to the cancer cells they are intended to treat, and they can harm healthy cells, leading to numerous adverse effects. Due to this non-specific targeting, it is not feasible to administer high doses that may harm healthy cells. Moreover, low doses can cause cancer cells to acquire resistance, thus making them hard to kill. A solution that could potentially enhance drug targeting and delivery lies in understanding the complexity of nanotechnology. Engineering pharmaceutical and natural products into nano-products can enhance the diagnosis and treatment of cancer. Novel nano-formulations such as liposomes, polymeric micelles, dendrimers, quantum dots, nano-suspensions, and gold nanoparticles have been shown to enhance the delivery of drugs. Improved delivery of chemotherapeutic agents targets cancer cells rather than healthy cells, thereby preventing undesirable side effects and decreasing chemotherapeutic drug resistance. Nanotechnology has also revolutionized cancer diagnosis by using nanotechnology-based imaging contrast agents that can specifically target and therefore enhance tumor detection. In addition to the delivery of drugs, nanotechnology can be used to deliver nutraceuticals like phytochemicals that have multiple properties, such as antioxidant activity, that protect cells from oxidative damage and reduce the risk of cancer. There have been multiple advancements and implications for the use of nanotechnology to enhance the delivery of both pharmaceutical and nutraceutical products in cancer prevention, diagnosis, and treatment.
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http://dx.doi.org/10.3390/biomedicines8090347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554840PMC
September 2020

A narrative review of buprenorphine in adult cancer pain.

Expert Rev Clin Pharmacol 2020 Oct 21;13(10):1159-1167. Epub 2020 Sep 21.

The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences , Rensselaer, NY, USA.

Introduction: Adult cancer pain is a disease state battled on a global scale. Proper pain management is essential to prevent health complications and promote patient well-being. Due to the opioid misuse crisis in the United States, providers are looking for alternatives to traditional opioids used for adult cancer pain. Buprenorphine has a unique pharmacologic profile, allowing it to be delivered in noninvasive ways; thus, it offers an alternative to traditional options. Randomized controlled trials have shown improved pain scores with transdermal buprenorphine, and they showed reductions in pain scores and increased improvement in quality of life scores versus other opioids. Sublingual buprenorphine has more limited, but promising data for reducing cancer pain.

Areas Covered: We provide a narrative review of pathophysiological pathways of pain in cancer, how they are treated, and the unique properties of buprenorphine. Guidelines addressing pain management during cancer treatment are assessed to identify buprenorphine's place in therapy. Recent literature reporting efficacy and safety of buprenorphine use in pain management during cancer treatment will be presented.

Expert Opinion: Current literature shows strong data for transdermal buprenorphine and promising data for sublingual buprenorphine. With this evidence, buprenorphine could have a more expanded role in managing adult cancer pain.
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http://dx.doi.org/10.1080/17512433.2020.1822163DOI Listing
October 2020

Characterization of tryptophan-containing dipeptides for anti-angiogenic effects.

Acta Physiol (Oxf) 2021 02 15;231(2):e13556. Epub 2020 Sep 15.

Institute of Physiology, Faculty of Medicine, Technische Universität Dresden, Dresden, Germany.

Aims: In the pathogenesis of several diseases, neo-angiogenesis is increased (e.g. tumour growth). The peptide L-glutamyl-L-tryptophan (EW/IM862) has been claimed to exhibit inhibitory effects on tumour growth in vivo. However, the potential role of natural peptides with respect to anti-angiogenic properties is unsettled. The current study explores anti-angiogenic effects of the dipeptides WL, EW, IW and WE.

Methods And Results: Using a bottom-up strategy, we first evaluated the effects of the peptides on VEGFR-2 signalling and quantified their effects in different angiogenesis assays. WL consistently had the strongest effects on phosphorylation of VEGFR-2 and downstream signalling. Therefore, this peptide was chosen in comparison with EW to further assess anti-angiogenic properties. However, sprout formation in three-dimensional (3D) fibrin gel bead assay was significantly inhibited by EW only. Furthermore, vessel sprouting in the mouse aortic ring assay was decreased by the presence of WL and EW compared to control. Results from a chorioallantoic membrane assay showed that under vascular endothelial growth factor (VEGF) stimulation WL and EW decreased the number of blood vessels versus control. These results were in line with those obtained in a matrigel plug assay. The VEGF-induced increase in the haemoglobin content was nearly abolished when treatment was combined with either WL or EW application. In the murine model of oxygen-induced retinopathy, WL exhibited a small albeit significant anti-angiogenic effect.

Conclusion: Comprehensive screening of WL suggests an anti-angiogenic effect, demonstrated in in vitro, ex vivo and in vivo models. Thus, WL is a dipeptide with potential anti-angiogenic effects and is worthy for further exploration.
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http://dx.doi.org/10.1111/apha.13556DOI Listing
February 2021

Molecular Mechanisms of Metal Toxicity in the Pathogenesis of Alzheimer's Disease.

Mol Neurobiol 2021 Jan 5;58(1):1-20. Epub 2020 Sep 5.

Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh, 11451, Saudi Arabia.

Alzheimer's disease (AD) is the most common form of dementia, which is progressively affecting elderly people. The dyshomeostasis of biometals and accumulation of toxic metals are usually observed in numerous neurodegenerative diseases including AD. In the central nervous system, metal imbalance-caused neurotoxic activities are usually linked with decreased enzymatic activities, increased aggregation of proteins, and oxidative stress, where a series of processes can result in neurodegeneration and cell death. Even though the relations between neurodegenerative diseases and biometal imbalance are still elusive, there is a growing interest in a group of major endogenous proteins that are associated with the transports of metals. Aberrant expression of these endogenous proteins is associated with the biometal imbalance and AD pathogenesis. Indeed, heavy metals are extremely toxic to the nervous system. Various studies have demonstrated that the toxic effects of heavy metals can result in amyloid beta (Aβ) aggregation, neurofibrillary tangles, and even loss of neurons. In this article, we have focused on the molecular processes through which exposure to biometals and toxic metals can play roles in AD pathogenesis.
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http://dx.doi.org/10.1007/s12035-020-02096-wDOI Listing
January 2021

Cancer-Associated Thrombosis: Risk Factors, Molecular Mechanisms, Future Management.

Clin Appl Thromb Hemost 2020 Jan-Dec;26:1076029620954282

The Pharmaceutical Research Institute, 1091Albany College of Pharmacy and Health Sciences, Rensselaer, NY, USA.

Venous thromboembolism (VTE) is a major health problem in patients with cancer. Cancer augments thrombosis and causes cancer-associated thrombosis (CAT) and vice versa thrombosis amplifies cancer progression, termed thrombosis-associated cancer (TAC). Risk factors that lead to CAT and TAC include cancer type, chemotherapy, radiotherapy, hormonal therapy, anti-angiogenesis therapy, surgery, or supportive therapy with hematopoietic growth factors. There are some other factors that have an effect on CAT and TAC such as tissue factor, neutrophil extracellular traps (NETs) released in response to cancer, cancer procoagulant, and cytokines. Oncogenes, estrogen hormone, and thyroid hormone with its integrin αvβ3 receptor promote angiogenesis. Lastly, patient-related factors can play a role in development of thrombosis in cancer. Low-molecular-weight heparin and direct oral anticoagulants (DOACs) are used in VTE prophylaxis and treatment rather than vitamin K antagonist. Now, there are new directions for potential management of VTE in patients with cancer such as euthyroid, blockade of thyroid hormone receptor on integrin αvβ3, sulfated non-anticoagulant heparin, inhibition of NETs and stratifying low and high-risk patients with significant bleeding problems with DOACs.
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http://dx.doi.org/10.1177/1076029620954282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7476343PMC
June 2021

Challenges in the Management of Sickle Cell Disease During SARS-CoV-2 Pandemic.

Clin Appl Thromb Hemost 2020 Jan-Dec;26:1076029620955240

The Pharmaceutical Research Institute, 1091Albany College of Pharmacy and Health Sciences, Rensselaer, NY, USA.

The management of sickle cell disease (SCD) and its complications in the COVID-19 era is very challenging. The recurrent sickling process in SCD causes tissue hypoxemia and micro-infarcts, resulting in end organ damage. Since the outbreak of SARS-CoV-2 pandemic, little data has been published about SCD concerning clinical presentation with COVID-19 and management. Hydroxyurea has been the cornerstone of management in children and adults with SCD, with evidence of its effect on controlling end organ damage. There are several anti-sickling drugs that have been approved recently that might have an additive value toward the management of SCD and its complications. The role of simple and exchange transfusions is well established and should always be considered in the management of various complications. The value of convalescent plasma has been demonstrated in small case series, but large randomized controlled studies are still awaited. Immunomodulatory agents may play a role in reducing the damaging effects of cytokines storm that contributes to the morbidity and mortality in advanced cases. Prophylactic anticoagulation should be considered in every management protocol because SCD and COVID-19 are thrombogenic conditions. Management proposals of different presentations of patients with SCD and COVID-19 are outlined.
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http://dx.doi.org/10.1177/1076029620955240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7476329PMC
September 2020

A New Eucalyptol-Rich Lavender ( L.) Essential Oil: Emerging Potential for Therapy against Inflammation and Cancer.

Molecules 2020 Aug 12;25(16). Epub 2020 Aug 12.

The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, New York, NY 12144, USA.

Background/aim: natural products are a potential source for drug discovery and development of cancer chemoprevention. Considering that drugs currently available for the treatment of inflammatory and cancer conditions show undesirable side effects, this research was designed to evaluate, for the first time, the in vitro anticancer activity of Algerian essential oil (LSEO) against different cancer cell lines, as well as its in vitro and in vivo topical and acute anti-inflammatory properties.

Materials And Methods: the LSEO was extracted by steam distillation, and chemical composition analysis was performed using gas chromatography. The main compounds identified in LSEO were oxygenated monoterpenes, such as 1,8-Cineole (61.36%). LSEO exhibited a potent anti-inflammatory activity using the xylene-induced mouse ear edema model.

Results: LSEO (200 and 20 mg/kg) was able to significantly reduce ( < 0.05) the carrageenan-induced paw edema with a similar effect to that observed for the positive control. Topical application of LSEO at doses of 82 and 410 mg/kg significantly reduced acute ear edema in 51.4% and 80.1% of the mice, respectively. Histological analysis confirmed that LSEO inhibited the skin inflammatory response. Moreover, LSEO was tested for its antitumor activity against different cancer cell lines. LSEO was found to be significantly active against human gastric adenocarcinoma (AGS), Melanoma MV3, and breast carcinoma MDA-MB-231 cells, with median inhibitory concentration (IC) values of 0.035 ± 0.018, 0.06 ± 0.022 and 0.259 ± 0.089 µL/mL, respectively. Altogether, these results open a new field of investigation into the characterization of the molecules involved in anti-proliferative processes.

Conclusion: We suggest that LSEO, with 1,8-Cineole as the major active component, is a promising candidate for use in skin care products with anti-inflammatory and anticancer properties. The results of this study may provide an experimental basis for further systematic research, rational development, and clinical utilization of lavender resources.
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http://dx.doi.org/10.3390/molecules25163671DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463424PMC
August 2020

Emerging Promise of Cannabinoids for the Management of Pain and Associated Neuropathological Alterations in Alzheimer's Disease.

Front Pharmacol 2020 22;11:1097. Epub 2020 Jul 22.

Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia.

Alzheimer's disease (AD) is an irreversible chronic neurodegenerative disorder that occurs when neurons in the brain degenerate and die. Pain frequently arises in older patients with neurodegenerative diseases including AD. However, the presence of pain in older people is usually overlooked with cognitive dysfunctions. Most of the times dementia patients experience moderate to severe pain but the development of severe cognitive dysfunctions tremendously affects their capability to express the presence of pain. Currently, there are no effective treatments against AD that emphasize the necessity for increasing research to develop novel drugs for treating or preventing the disease process. Furthermore, the prospective therapeutic use of cannabinoids in AD has been studied for the past few years. In this regard, targeting the endocannabinoid system has considered as a probable therapeutic strategy to control several associated pathological pathways, such as mitochondrial dysfunction, excitotoxicity, oxidative stress, and neuroinflammation for the management of AD. In this review, we focus on recent studies about the role of cannabinoids for the treatment of pain and related neuropathological changes in AD.
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http://dx.doi.org/10.3389/fphar.2020.01097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7387504PMC
July 2020

Neurodegenerative Diseases and Cell Reprogramming.

Mol Neurobiol 2020 Nov 12;57(11):4767-4777. Epub 2020 Aug 12.

The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, 1 Discovery Drive, Rensselaer, NY, 12144, USA.

Neurodegenerative diseases have different types according to the onset of the disease, the time course, and the underlying pathology. Although the dogma that brain cells cannot regenerate has changed, the normal regenerative process of the brain is usually not sufficient to restore brain tissue defects after different pathological insults. Stem cell therapy and more recently cell reprogramming could achieve success in the process of brain renewal. This review article presents recent advances of stem cell therapies in neurodegenerative diseases and the role of cell reprogramming in the scope of optimizing a confined condition that could direct signaling pathways of the cell toward a specific neural lineage. Further, we will discuss different types of transcriptional factors and their role in neural cell fate direction.
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http://dx.doi.org/10.1007/s12035-020-02039-5DOI Listing
November 2020

Pomegranate () Fruit Extract Suppresses Cancer Progression and Tumor Angiogenesis of Pancreatic and Colon Cancer in Chick Chorioallantoic Membrane Model.

Nutr Cancer 2021 6;73(8):1350-1356. Epub 2020 Aug 6.

Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Albany, New York, USA.

Pomegranate fruit extract contains many polyphenols and flavonoids of diverse biological importance including anticancer potential. In cancer, the angiogenesis process facilitates solid cancer growth and metastasis. Here, the antiangiogenic effect of pomegranate fruit extract against human pancreatic cancer (Suit-2) and colon (colo205) cell lines in the chick chorioallantoic membrane (CAM) model was studied along with the effect of pomegranate fruit extract on fibroblast growth factor (FGF2). Pomegranate fruit extract significantly reduced the tumor weight and hemoglobin content in CAM models of pancreatic Suit-2 and colon colo205.
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http://dx.doi.org/10.1080/01635581.2020.1800768DOI Listing
September 2021

NDAT Targets PI3K-Mediated PD-L1 Upregulation to Reduce Proliferation in Gefitinib-Resistant Colorectal Cancer.

Cells 2020 08 3;9(8). Epub 2020 Aug 3.

Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Albany, NY 12208, USA.

The property of drug-resistance may attenuate clinical therapy in cancer cells, such as chemoresistance to gefitinib in colon cancer cells. In previous studies, overexpression of PD-L1 causes proliferation and metastasis in cancer cells; therefore, the PD-L1 pathway allows tumor cells to exert an adaptive resistance mechanism in vivo. Nano-diamino-tetrac (NDAT) has been shown to enhance the anti-proliferative effect induced by first-line chemotherapy in various types of cancer, including colorectal cancer (CRC). In this work, we attempted to explore whether NDAT could enhance the anti-proliferative effect of gefitinib in CRC and clarified the mechanism of their interaction. The MTT assay was utilized to detect a reduction in cell proliferation in four primary culture tumor cells treated with gefitinib or NDAT. The gene expression of and other tumor growth-related molecules were quantified by quantitative polymerase chain reaction (qPCR). Furthermore, the identification of PI3K and PD-L1 in treated CRC cells were detected by western blotting analysis. PD-L1 presentation in HCT116 xenograft tumors was characterized by specialized immunohistochemistry (IHC) and the hematoxylin and eosin stain (H&E stain). The correlations between the change in PD-L1 expression and tumorigenic characteristics were also analyzed. The was highly expressed in Colo_160224 rather than in the other three primary CRC cells and HCT-116 cells. Moreover, the expression was decreased by gefitinib (1 µM and 10 µM) in two cells (Colo_150624 and 160426), but 10 µM gefitinib stimulated expression in gefitinib-resistant primary CRC Colo_160224 cells. Inactivated PI3K reduced expression and proliferation in CRC Colo_160224 cells. Gefitinib didn't inhibit expression and PI3K activation in gefitinib-resistant Colo_160224 cells. However, NDAT inhibited PI3K activation as well as PD-L1 accumulation in gefitinib-resistant Colo_160224 cells. The combined treatment of NDAT and gefitinib inhibited pPI3K and PD-L1 expression and cell proliferation. Additionally, NDAT reduced PD-L1 accumulation and tumor growth in the HCT116 ( mutant) xenograft experiment. Gefitinib might suppress expression but did not inhibit proliferation through PI3K in gefitinib-resistant primary CRC cells. However, NDAT not only down-regulated PD-L1 expression via blocking PI3K activation but also inhibited cell proliferation in gefitinib-resistant CRCs.
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http://dx.doi.org/10.3390/cells9081830DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464180PMC
August 2020

Solvent-free microwave extraction: an eco-friendly and rapid process for green isolation of essential oil from lemongrass.

Nat Prod Res 2020 Jul 24:1-4. Epub 2020 Jul 24.

The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY, USA.

The extraction of lemongrass essential oil (LGEO) using large quantities of solvents makes this extraction a hazardous and environmentally unfriendly procedure. Our aim was to find a suitable method for the improvement of its extraction and its quality. Solvent-Free Microwave Extraction (SFME) is a combination of dry distillation and microwave heating. SFME of LGEO was compared with conventional extraction hydrodistillation (HD). SFME is quicker than conventional HD. An extraction time of 15 min with SFME provided a yield of 0.6% comparable with that obtained after 120 min using HD. The composition of these oils revealed that the main components obtained with HD and SFME were both geranial (59.93% vs 44.59%, respectively). The quality of lemongrass is determined by its citral content, and a higher amount of citral was present in SFME oil (74%) in comparison with HD oil (60%). SFME is a green and a promising technology for the extraction of essential oils.
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http://dx.doi.org/10.1080/14786419.2020.1795852DOI Listing
July 2020

Actions of L-thyroxine (T4) and Tetraiodothyroacetic Acid (Tetrac) on Gene Expression in Thyroid Cancer Cells.

Genes (Basel) 2020 07 7;11(7). Epub 2020 Jul 7.

Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY 12144, USA.

The clinical behavior of thyroid cancers is seen to reflect inherent transcriptional activities of mutated genes and trophic effects on tumors of circulating pituitary thyrotropin (TSH). The thyroid hormone, L-thyroxine (T4), has been shown to stimulate proliferation of a large number of different forms of cancer. This activity of T4 is mediated by a cell surface receptor on the extracellular domain of integrin αvβ3. In this brief review, we describe what is known about T4 as a circulating trophic factor for differentiated (papillary and follicular) thyroid cancers. Given T4's cancer-stimulating activity in differentiated thyroid cancers, it was not surprising to find that genomic actions of T4 were anti-apoptotic. Transduction of the T4-generated signal at the integrin primarily involved mitogen-activated protein kinase (MAPK). In thyroid C cell-origin medullary carcinoma of the thyroid (MTC), effects of thyroid hormone analogues, such as tetraiodothyroacetic acid (tetrac), include pro-angiogenic and apoptosis-linked genes. Tetrac is an inhibitor of the actions of T4 at αvβ3, and it is assumed, but not yet proved, that the anti-angiogenic and pro-apoptotic actions of tetrac in MTC cells are matched by T4 effects that are pro-angiogenic and anti-apoptotic. We also note that papillary thyroid carcinoma cells may express the leptin receptor, and circulating leptin from adipocytes may stimulate tumor cell proliferation. Transcription was stimulated by leptin in anaplastic, papillary, and follicular carcinomas of genes involved in invasion, such as matrix metalloproteinases (MMPs). In summary, thyroid hormone analogues may act at their receptor on integrin αvβ3 in a variety of types of thyroid cancer to modulate transcription of genes relevant to tumor invasiveness, apoptosis, and angiogenesis. These effects are independent of TSH.
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http://dx.doi.org/10.3390/genes11070755DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7396989PMC
July 2020

Coronaviruses and Integrin αvβ3: Does Thyroid Hormone Modify the Relationship?

Endocr Res 2020 Aug;45(3):210-215

Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences , Rensselaer, NY, USA.

Background: Uptake of coronaviruses by target cells involves binding of the virus by cell ectoenzymes. For the etiologic agent of COVID-19 (SARS-CoV-2), a receptor has been identified as angiotensin-converting enzyme-2 (ACE2). Recently it has been suggested that plasma membrane integrins may be involved in the internalization and replication of clinically important coronaviruses. For example, integrin αvβ3 is involved in the cell uptake of a model porcine enteric α-coronavirus that causes human epidemics. ACE2 modulates the intracellular signaling generated by integrins.

Objective: We propose that the cellular internalization of αvβ3 applies to uptake of coronaviruses bound to the integrin, and we evaluate the possibility that clinical host T4 may contribute to target cell uptake of coronavirus and to the consequence of cell uptake of the virus.

Discussion And Conclusions: The viral binding domain of the integrin is near the Arg-Gly-Asp (RGD) peptide-binding site and RGD molecules can affect virus binding. In this same locale on integrin αvβ3 is the receptor for thyroid hormone analogues, particularly, L-thyroxine (T4). By binding to the integrin, T4 has been shown to modulate the affinity of the integrin for other proteins, to control internalization of αvβ3 and to regulate the expression of a panel of cytokine genes, some of which are components of the 'cytokine storm' of viral infections. If T4 does influence coronavirus uptake by target cells, other thyroid hormone analogues, such as deaminated T4 and deaminated 3,5,3'-triiodo-L-thyronine (T3), are candidate agents to block the virus-relevant actions of T4 at integrin αvβ3 and possibly restrict virus uptake.
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http://dx.doi.org/10.1080/07435800.2020.1767127DOI Listing
August 2020

Nongenomic Actions of Thyroid Hormone: The Integrin Component.

Physiol Rev 2021 01 25;101(1):319-352. Epub 2020 Jun 25.

Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, New York; Department of Medicine, Albany Medical College, Albany, New York; Ph.D. Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan; Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan; and Traditional Herbal Medicine Research Center of Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan.

The extracellular domain of plasma membrane integrin αvβ3 contains a cell surface receptor for thyroid hormone analogues. The receptor is largely expressed and activated in tumor cells and rapidly dividing endothelial cells. The principal ligand for this receptor is l-thyroxine (T), usually regarded only as a prohormone for 3,5,3'-triiodo-l-thyronine (T), the hormone analogue that expresses thyroid hormone in the cell nucleus via nuclear receptors that are unrelated structurally to integrin αvβ3. At the integrin receptor for thyroid hormone, T regulates cancer and endothelial cell division, tumor cell defense pathways (such as anti-apoptosis), and angiogenesis and supports metastasis, radioresistance, and chemoresistance. The molecular mechanisms involve signal transduction via mitogen-activated protein kinase and phosphatidylinositol 3-kinase, differential expression of multiple genes related to the listed cell processes, and regulation of activities of other cell surface proteins, such as vascular growth factor receptors. Tetraiodothyroacetic acid (tetrac) is derived from T and competes with binding of T to the integrin. In the absence of T, tetrac and chemically modified tetrac also have anticancer effects that culminate in altered gene transcription. Tumor xenografts are arrested by unmodified and chemically modified tetrac. The receptor requires further characterization in terms of contributions to nonmalignant cells, such as platelets and phagocytes. The integrin αvβ3 receptor for thyroid hormone offers a large panel of cellular actions that are relevant to cancer biology and that may be regulated by tetrac derivatives.
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http://dx.doi.org/10.1152/physrev.00038.2019DOI Listing
January 2021

Dual Targeting of Norepinephrine Transporter (NET) Function and Thyrointegrin αvβ3 Receptors in the Treatment of Neuroblastoma.

J Med Chem 2020 07 7;63(14):7653-7662. Epub 2020 Jul 7.

Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, 1 Discovery Drive (Room 238), Rensselaer, New York 12144, United States.

Therapeutic targeting of the norepinephrine transporter (NET) function with benzylguanidine (BG), conjugated with the high-affinity thyrointegrin αvβ3 antagonist triazole tetraiodothyroacetic acid, TAT, via noncleavable bonding to poly(ethylene glycol) (PEG) (P) might allow for effective treatment options in neuroblastoma. BG-P-TAT is a dual-targeting agent, targeting the NET function and the thyrointegrin αvβ3 receptors that are overexpressed in neuroblastoma and other neuroendocrine tumors. Various cancer cells and actively dividing tumor-endothelial cells express the thyrointegrin αvβ3 receptors. In this work, the novel compound BG-P-TAT was synthesized and evaluated in the neuroblastoma SK-N-FI cell line for improved targeting and to offer a new strategy for patients with neuroblastoma. BG-P-TAT demonstrated significant suppression of neuroblastoma tumor progression, growth, and viability in a dose-dependent manner. In conclusion, BG-P-TAT represents a potential lead candidate for the treatment of neuroblastoma and other neuroendocrine tumors.
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http://dx.doi.org/10.1021/acs.jmedchem.0c00537DOI Listing
July 2020

Quercetin Attenuates Pancreatic and Renal D-Galactose-Induced Aging-Related Oxidative Alterations in Rats.

Int J Mol Sci 2020 Jun 18;21(12). Epub 2020 Jun 18.

Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY 12144, USA.

Aging is an oxidative stress-associated process that progresses with age. Our aim is to delay or attenuate these oxidative alterations and to keep individuals healthy as they age using natural compounds supplementation. Therefore, we conducted the present study to investigate the protective potentials of quercetin against D-galactose (D-gal)-associated oxidative alterations that were induced experimentally in male Wistar rats. Forty-five rats were randomly allocated into five groups of nine rats each. The groups were a control group that was reared on a basal diet and injected subcutaneously with 120 mg D-gal dissolved in physiological saline solution (0.9% NaCl) per kg body weight daily and quercetin-treated groups that received the same basal diet and subcutaneous daily D-gal injections were supplemented orally with 25, 50, and 100 mg of quercetin per kg body weight for 42 days. Pancreatic and renal samples were subjected to histopathological, immunohistochemical, and relative mRNA expression assessments. Aging (, , , and ), apoptotic (, , and caspase-3 protein), proliferative (Ki67 protein), antiapoptotic ( and Bcl2 protein), inflammatory (, , and ), antioxidant (), and functional markers ( and genes and insulin, glucagon, and podocin proteins) were determined to evaluate the oxidative alterations induced by D-gal and the protective role of quercetin. D-gal caused oxidative alterations of the pancreas and kidneys observed via upregulations of aging, apoptotic, and inflammatory markers and downregulated the antiapoptotic, proliferative, antioxidant, and functional markers. Quercetin potentially attenuated these aging-related oxidative alterations in a dose-dependent manner. Finally, we can conclude that quercetin supplementation is considered as a promising natural protective compound that could be used to delay the aging process and to maintain human health.
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http://dx.doi.org/10.3390/ijms21124348DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352460PMC
June 2020

The potential role of pomegranate and its nano-formulations on cerebral neurons in aluminum chloride induced Alzheimer rat model.

Saudi J Biol Sci 2020 Jul 7;27(7):1710-1716. Epub 2020 May 7.

Department of Otolaryngology, Head and Neck Surgery, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.

The oxidative stress leading to degenerative changes in the brain of Alzheimer's disease (AD) is evident. Our aim was to evaluate the therapeutic and protective effects of pomegranate extract (PE) and pomegranate extract-loaded nanoparticles (PE nano) in an AlCl 3-induced AD rat model. Nanoparticles were synthesized with a PE load of 0.68% w/w, and 70 male Wistar rats were divided into 7 groups: Group I was the control, Group II received PE., Group III received PE nano for 2 weeks, Group IV received AlCl 3 (50 mg/kg) daily orally for 4 weeks, Group V received PE for 2 weeks, Group VI received PE nano for 2 weeks, and Groups V and VI were started after AlCl 3 administration was stopped. Group VII received PE for 2 weeks and was stopped before AlCl 3 was administered. The Results revealed that the discrimination index in the novel object recognition test was the least in AD rat model but increased in cases protected with PE treated with PE nano. Similar results were shown based on calculating the brain weight/body weight percent. The biomarkers of antioxidant activity (catalase, glutathione and total antioxidant activity) in brain homogenate were significantly increased in groups treated with either PE or PE nano. The thiobarbituric acid reactive substance measured to estimate lipid peroxidation was significantly increased in AD rat model and decreased in groups protected with PE or treated with PE nano. Histopathological studies using hematoxylin and eosin, cresyl violet, and silver stains revealed hyaline degeneration, chromatolysis, and hallmarks of AD; neurofibrillary tangles and the senile plaques in brains of AD rat model. Restoration of the histological architecture, Nissl granules, and minimal appearance of hallmarks of AD characterized brains treated with PE or PE nano. In conclusion, PE was more effective as a protectant than a therapeutic measure in alleviating the antioxidant, lipid peroxidative effects and histopathological hallmarks in AD brains. But, the therapeutic PE-loaded nanoparticles increased the efficacy of active components and produced similar results as the protective PE.
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http://dx.doi.org/10.1016/j.sjbs.2020.04.045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7296487PMC
July 2020

β-glucan administration improves growth performance and gut health in New Zealand White and APRI rabbits with different breed responses.

PLoS One 2020 10;15(6):e0234076. Epub 2020 Jun 10.

Department of Biochemistry, Faculty of Veterinary Medicine, Damanhour University, Damanhour, Egypt.

This study investigated the effects of oral administration of β-glucan 1,3 (pharmaceutical grade 10%) on growth performance and carcass traits in two breeds of weanling rabbits adapted to survive in Egypt, New Zealand White (NZW) and Animal Production Research Institute (APRI) rabbits, with special attention to relative mRNA expression of interleukins and antioxidant enzyme genes, biochemical, and histological alterations. Oral administration of β-glucan with doses 0.25 and 0.5 ml per one-liter of drinking water significantly accelerated body weight gain (BWG) in both rabbits' breeds, reduced total feed consumption (FC), and reduced feed conversion ratio (FCR), especially the 0.5 ml per one-liter dose in both rabbit breeds. There are remarkable differences in all the growth performance traits due to breed effect. The interaction effect between β-glucan and breed significantly improved BWG, FC, and FCR. There were non-significant differences in all carcass traits studied due to oral administration of β-glucan with both doses, except in dressing percentages. The highest of the dressing percentages were observed at doses 0.25 ml per one-liter (51%) and 0.5 ml per one-liter (52%) compared with control (50%). Our findings show significant variations in the final BW, total daily gain, feed consumption, and total feed conversion ratio between NZW and APRI rabbits. Absence of significant differences in the hot carcass weight and dressing percentage between the genetic groups had been reported in this study. Supplementing NZW and APRI rabbits with β-glucan increased blood total protein and globulin. The duodenal villi dimensions, splenic lymphoid diameter, muscular fiber diameter, and muscular glycogen areas were significantly increased by β-glucan administration. Expression of intestinal interleukin-18 (IL-18) in NZW rabbits treated with 0.25 and 0.5 doses of β-glucan was significantly upregulated and enhanced the immune response. β-glucan upregulated the expression of intestinal occludin mRNA particularly at dose 0.5 β-glucan as well as upregulated intestinal superoxide dismutase 1 (SOD1) and glutathione peroxidase 1 (GPx1), which modulates anti-inflammatory and antioxidant properties. In conclusion, oral administration of β-glucan at a dose of 0.25 or 0.5 ml per one-liter drinking water provided beneficial effects in the growth performance and health status of rabbits.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0234076PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7286524PMC
August 2020

Molecular Insight into the Therapeutic Promise of Targeting for Alzheimer's Disease.

Oxid Med Cell Longev 2020 15;2020:5086250. Epub 2020 May 15.

Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.

Alzheimer's disease (AD) is a progressive neurodegenerative disease that causes chronic cognitive dysfunction. Most of the AD cases are late onset, and the apolipoprotein E () isoform is a key genetic risk factor. The gene has 3 key alleles in humans including , , and . Among them, is the most potent genetic risk factor for late-onset AD (LOAD), while has a defensive effect. Research data suggest that leads to the pathogenesis of AD through various processes such as accelerated beta-amyloid aggregations that raised neurofibrillary tangle formation, cerebrovascular diseases, aggravated neuroinflammation, and synaptic loss. However, the precise mode of actions regarding in what way leads to AD pathology remains unclear. Since contributes to several pathological pathways of AD, targeting might serve as a promising strategy for the development of novel drugs to combat AD. In this review, we focus on the recent studies about -targeted therapeutic strategies that have been advanced in animal models and are being prepared for use in humans for the management of AD.
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http://dx.doi.org/10.1155/2020/5086250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7245681PMC
December 2020

Nanoformulated Ajwa (Phoenix Dactylifera) Bioactive Compounds Improve the Safety of Doxorubicin without Compromising its Anticancer Efficacy in Breast Cancer.

Molecules 2020 Jun 3;25(11). Epub 2020 Jun 3.

Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY 12144, USA.

One of the major causes of women's death in the world is breast cancer. Consequently, numerous regimens for the control of this severe disease have been created. The chemotherapeutic agent doxorubicin (DOX) is frequently used to treat breast cancer, but DOX can also cause cardiotoxic effects that lead to heart failure. Therefore, many research studies have been done to find a natural product that effectively potentiates or does not interfere with DOX's anticancer effect and protects against its cardiotoxicity. We studied the impact of combined nanoformulated Ajwa (Phoenix dactylifera) selected bioactive compounds (BAC) rutin (R) and quercetin (Q) in nude mice breast cancer xenografts on DOX-mediated anticancer efficacy. We also studied if this Ajwa BAC could safeguard against DOX-mediated cardiomyopathies by evaluating plasma cardiac troponin-I (cTn-I) levels and cardiac histopathology. Nanoformulated Ajwa BAC effectively alleviated weight loss induced by DOX in mice and significantly decreased the elevated cTn-I. Furthermore, 5 mg RQ-NPs/kg of nude mice that subcutaneously daily injected for 11 days, attenuated the histopathological alterations induced in cardiac muscles due to DOX without any interference with the anticancer effects of DOX against breast cancer.
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http://dx.doi.org/10.3390/molecules25112597DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7321378PMC
June 2020

Thymoquinone-chemotherapeutic combinations: new regimen to combat cancer and cancer stem cells.

Naunyn Schmiedebergs Arch Pharmacol 2020 09 26;393(9):1581-1598. Epub 2020 May 26.

Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY, 12144, USA.

Cancer is a worldwide disease that causes millions of cases of mortality and morbidity. The major problem associated with the cancer is its resistance to conventional therapy and a high relapse rate. The use of chemotherapy to treat cancer began at the start of the twentieth century with attempts to control cancer. In time advance, many cancer chemotherapeutic agents have been developed for cancer treatment with different mechanisms of action including the alkylating agents, antimetabolites, antimicrotubule, topoisomerase inhibitors, and cytotoxic antibiotics, all of which have toxic effects toward normal cells in the body. Here, we reviewed chemotherapeutics' anticancer role potentiation and safety by thymoquinone (TQ) alone or in combination with the most common therapeutic drugs. Our search was done through PubMed, Science Direct, Springer Link, Taylor & Francis Online, Wiley Online Library, Nature publication group, SAGE Journals, and Web of Science databases. We recognized that TQ-chemotherapeutics combination increased chemo-modulation to the anticancer effect of different chemotherapeutics and protected the normal body cells from the toxic injuries that are induced by chemotherapeutics based on its antioxidant power. Moreover, the current study investigates the possible combinatory effect of TQ and chemotherapeutics to control cancer stem cells through molecular docking targeting of wingless/integrated (Wnt) and Hedgehog (Hh). We found that TQ modulates the Wnt and Hh pathways, by binding with tankyrase-2 and smoothened 7TM receptor, respectively, more efficiently than most chemotherapeutics drugs, while methotrexate showed high-binding affinity compared with TQ. Therefore, we encourage researchers to investigate the chemo-modulatory potential and protective effects of TQ in combination with chemotherapeutics for either cancer or cancer stem cell treatment.
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http://dx.doi.org/10.1007/s00210-020-01898-yDOI Listing
September 2020

Role and Mechanisms of RAGE-Ligand Complexes and RAGE-Inhibitors in Cancer Progression.

Int J Mol Sci 2020 May 20;21(10). Epub 2020 May 20.

The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY 12144, USA.

Interactions of the receptor for advanced glycation end product (RAGE) and its ligands in the context of their role in diabetes mellitus, inflammation, and carcinogenesis have been extensively investigated. This review focuses on the role of RAGE-ligands and anti-RAGE drugs capable of controlling cancer progression. Different studies have demonstrated interaction of RAGE with a diverse range of acidic (negatively charged) ligands such as advanced glycation end products (AGEs), high-mobility group box1 (HMGB1), and S100s, and their importance to cancer progression. Some RAGE-ligands displayed effects on anti- and pro-apoptotic proteins through upregulation of the phosphatidylinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR), mitogen-activated protein kinases (MAPKs), matrix metalloproteinases (MMPs), vascular endothelial growth factor (VEGF), and nuclear factor kappa B (NF-B) pathways, while downregulating p53 in cancer progression. In addition, RAGE may undergo ligand-driven multimodal dimerization or oligomerization mediated through self-association of some of its subunits. We conclude our review by proposing possible future lines of study that could result in control of cancer progression through RAGE inhibition.
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http://dx.doi.org/10.3390/ijms21103613DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7279268PMC
May 2020

Novel Anti-Alzheimer's Therapeutic Molecules Targeting Amyloid Precursor Protein Processing.

Oxid Med Cell Longev 2020 29;2020:7039138. Epub 2020 Apr 29.

Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.

Alzheimer's disease (AD) is the most common cause of dementia among older people, and the prevalence of this disease is estimated to rise quickly in the upcoming years. Unfortunately, almost all of the drug candidates tested for AD until now have failed to exhibit any efficacy. Henceforth, there is an increased necessity to avert and/or slow down the advancement of AD. It is known that one of the major pathological characteristics of AD is the presence of senile plaques (SPs) in the brain. These SPs are composed of aggregated amyloid beta (A), derived from the amyloid precursor protein (APP). Pharmaceutical companies have conducted a number of studies in order to identify safe and effective anti-A drugs to combat AD. It is known that -, -, and -secretases are the three proteases that are involved in APP processing. Furthermore, there is a growing interest in these proteases, as they have a contribution to the modulation and production of A. It has been observed that small compounds can be used to target these important proteases. Indeed, these compounds must satisfy the common strict requirements of a drug candidate targeted for brain penetration and selectivity toward different proteases. In this article, we have focused on the auspicious molecules which are under development for targeting APP-processing enzymes. We have also presented several anti-AD molecules targeting A accumulation and phosphorylation signaling in APP processing. This review highlights the structure-activity relationship and other physicochemical features of several pharmacological candidates in order to successfully develop new anti-AD drugs.
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http://dx.doi.org/10.1155/2020/7039138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7206886PMC
January 2021

Antiviral Activity of Chitosan Nanoparticles Encapsulating Curcumin Against Hepatitis C Virus Genotype 4a in Human Hepatoma Cell Lines.

Int J Nanomedicine 2020 22;15:2699-2715. Epub 2020 Apr 22.

The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY, USA.

Purpose: Current direct-acting antiviral agents for treatment of hepatitis C virus genotype 4a (HCV-4a) have been reported to cause adverse effects, and therefore less toxic antivirals are needed. This study investigated the role of curcumin chitosan (CuCs) nanocomposite as a potential anti-HCV-4a agent in human hepatoma cells Huh7.

Methods: Docking of curcumin and CuCs nanocomposite and binding energy calculations were carried out. Chitosan nanoparticles (CsNPs) and CuCs nanocomposite were prepared with an ionic gelation method and characterized with TEM, zeta size and potential, and HPLC to calculate encapsulation efficiency. Cytotoxicity studies were performed on Huh7 cells using MTT assay and confirmed with cellular and molecular assays. Anti-HCV-4a activity was determined using real-time PCR and Western blot.

Results: The strength of binding interactions between protein ligand complexes gave scores with NS3 protease, NS5A polymerase, and NS5B polymerase of -124.91, -159.02, and -129.16, for curcumin respectively, and -68.51, -54.52, and -157.63 for CuCs nanocomposite, respectively. CuCs nanocomposite was prepared at sizes 29-39.5 nm and charges of 33 mV. HPLC detected 4% of curcumin encapsulated into CsNPs. IC50 was 8 µg/mL for curcumin and 25 µg/mL for the nanocomposite on Huh7 but was 25.8 µg/mL and 34 µg/mL on WISH cells. CsNPs had no cytotoxic effect on tested cell lines. Apoptotic genes' expression revealed the caspase-dependent pathway mechanism. CsNPs and CuCs nanocomposite demonstrated 100% inhibition of viral entry and replication, which was confirmed with HCV core protein expression.

Conclusion: CuCs nanocomposite inhibited HCV-4a entry and replication compared to curcumin alone, suggesting its potential role as an effective therapeutic agent.
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http://dx.doi.org/10.2147/IJN.S241702DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7184126PMC
July 2020

Functionalized nano-targeted moieties in management of prostate cancer.

Future Oncol 2020 May 15;16(13):869-883. Epub 2020 Apr 15.

The Pharmaceutical Research Institute, Albany College of Pharmacy & Health Sciences, 1 Discovery Drive, Rensselaer, NY 12144 USA.

Multimodal properties of nanoparticles, such as simultaneously carrying drugs and/or diagnostic probes for site-specific delivery, make them excellent carriers for diagnosis and treatment of prostate cancer. Advantages are high permeability and selectivity to malignant cells to reduce systemic toxicity of chemotherapeutic drugs. Based on a review of current literature, the lack of efficient and highly specific prostate cancer cell targeting moieties is hindering successful prostate cancer-targeted drug delivery systems. Highly specific nano-targeting moieties as drug delivery vehicles might improve chemotherapeutic delivery via targeting to specific receptors expressed on the surface of prostate cancer cells. This review describes nano-targeting moieties for management of prostate cancer and its cancer stem cells. Descriptions of targeting moieties using anti-prostate-specific membrane antigen, aptamer, anti-cluster of differentiation 24/44, folic acid and other targeting strategies are highlighted. Current research results are promising and may yield development of next-generation nanoscale theragnostic targeted modalities for prostate cancer treatment.
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http://dx.doi.org/10.2217/fon-2019-0635DOI Listing
May 2020

Nanoformulated Bioactive Compounds Derived from Different Natural Products Combat Pancreatic Cancer Cell Proliferation.

Int J Nanomedicine 2020 31;15:2259-2268. Epub 2020 Mar 31.

Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY 12144, USA.

Purpose: This study was designed to determine the potential effect of nanoencapsulated bioactive compounds from different natural sources on human pancreatic cancer.

Background: Pancreatic cancer carries the highest fatality rate among all human cancers because of its high metastatic potential and late presentation at the time of diagnosis. Hence there is a need for improved methods to prevent and treat it. Natural products, such as 3, 3'-diindolylmethane (DIM) and ellagic acid (EA) demonstrated anticancer efficacy against various cancer types. However, DIM is insoluble. Hence, using nanotechnology to encapsulate these compounds in combination with EA might improve their physical and chemical properties and their delivery to the cancer cells.

Methods: Human pancreatic cancer cells, namely SUIT2-luciferase transfected, were used to examine the effects of DIM or EA and their nanoformulation in poly(lactic-co-glycolic acid) (PLGA) and poly(ethylene glycol) (PEG) [PLGA-PEG] nanoparticles (NPs) on SUIT2-luciferase cell viability/proliferation over 24 hrs. Additionally, effects on tumor weight and angiogenesis were determined using the chick chorioallantoic membrane (CAM) tumor implant model.

Results: Both DIM and EA PLGA-PEG NPs resulted in rapid suppression of pancreatic cancer cell viability/proliferation within 24 hrs ( < 0.01), while the non-encapsulated DIM and EA did not show any significant effect on SUIT2 cancer cell viability or cell proliferation (MTT assay). In the CAM pancreatic cancer cell (SUIT2) implant model, results showed a greater suppression of tumor weight ( < 0.01), tumor cell viability, and tumor angiogenesis ( < 0.01) for DIM NPs and EA NPs and their combinations versus DIM or EA alone.

Conclusion: Nanoformulation of DIM and EA resulted in a more effective suppression of pancreatic cancer cell viability, pancreatic tumor weight, implanted cancer cell viability, and tumor angiogenesis as compared with these bioactive compounds alone.
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http://dx.doi.org/10.2147/IJN.S238256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7127850PMC
July 2020

Resveratrol and Its Nanoformulation Attenuate Growth and the Angiogenesis of Xenograft and Orthotopic Colon Cancer Models.

Molecules 2020 Mar 20;25(6). Epub 2020 Mar 20.

Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY 12144, USA.

Cancer is a multifactorial disorder that induces mortality worldwide, and the colorectal type is the third most common cancer globally. Resveratrol (RSV) is a natural compound with an effective anticancer effect, especially against colorectal cancer, and therefore numerous studies recommended its use in colorectal cancer prevention and treatment. The current study investigated the effect of either RSV or its nanoformulation (NP-RSV) on the growth and vascularity of xenograft and orthotopic mice models in colon cancer (COLO205-luc). Both RSV and NP-RSV induced significant reductions in tumor growth and the hemoglobin percentages of the tumor mass, but NP-RSV showed greater bioavailability and efficacy than RSV. Generally, we recommend using NP-RSV as a therapeutic to control colon cancer.
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http://dx.doi.org/10.3390/molecules25061412DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7144556PMC
March 2020
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