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Mohammad Z Haider,1 Amna Al-Mannai,1 Sally Al-Sirhan,1 Ahmed Elsabagh,1 Nasser Nasser,1 Noora Al-Quraishi,1 Amr Ouda,1 Khadija Erradi,1 Anas A Ashour,2 Ishita Gupta,1,3 Jazeel Abdulmajeed,4 Hamad E Al-Romaihi,4 Devendra Bansal,4 Omran AH Musa,4 Elmoubasher Abu Baker Abd Farag,4 Mohammed HJ Al-Thani,4 Ala-Eddin Al Moustafa1,3,5 1College of Medicine, QU Health, Qatar University, Doha, Qatar; 2Department of Internal Medicine, Hamad Medical Corporation, Doha, Qatar; 3Biomedical and Pharmaceutical Research Unit, QU Health, Qatar University, Doha, Qatar; 4Ministry of Public Health, Doha, Qatar; 5Biomedical Research Centre, Qatar University, Doha, QatarCorrespondence: Ala-Eddin Al Moustafa, College of Medicine, QU Health, Qatar University, PO Box 2713, Doha, Qatar, Tel +974 4403 7817, Fax +974 4403-3333, Email aalmoustafa@qu.edu.qaPurpose: Predisposition to acute illness from COVID-19 is suggested to correlate with cigarette smoking as it augments the risk of developing cardiovascular and respiratory illnesses, including infections. However, the effects of smoking on COVID-19 symptoms are not well described and controversial. In this study, we aim to explore the associations between smoking and COVID-19 symptoms.Subjects and Methods: A cross-sectional study using the Ministry of Public Health (MoPH), Qatar database was administered to a Qatari population with confirmed COVID-19 disease who filled in pre-defined phone-call questionnaire between 27th February 2020 and 31st December 2020. We analyzed 11,701 non-vaccinated COVID-19 individuals (2952 smokers and 8749 non-smokers) with confirmed RT-PCR test results. The association of smoking and the presence of symptoms as well as patient characteristics was calculated using Pearson’s Chi-square and Fisher’s exact tests, adjusting for potential covariates.Results: Compared with the non-smokers, symptomatic COVID-19 infection is significantly higher in smokers. In addition, we found fever as the most common symptom developed in COVID-19 patients followed by cough, headache, muscle ache, and sore throat. As compared to other symptoms, association of smoking with chills and abdominal pain was less evident (P < 0.05 and P < 0.001, respectively). However, both groups showed similar rates of developing cough.Conclusion: In conclusion, smoking is associated with COVID-19 symptoms frequency in non-vaccinated patients; nevertheless, further investigations are necessary to understand the mechanism of this association which could generate new targets for the management of COVID-19 in smoker patients.Keywords: COVID-19, smoking, frequency, Qatar, symptoms

Ala-Eddin Al Moustafa,1–4 Etienne Mfoumou,5 Dacian E Roman,3 Vahe Nerguizian,6 Anas Alazzam,7 Ion Stiharu,3 Amber Yasmeen8 1College of Medicine & Biomedical Research Centre, Qatar University, Doha, Qatar; 2Oncology Department, McGill University, 3Mechanical and Industrial Engineering Department, Concordia University, Montreal, QC, Canada; 4Syrian Research Cancer Centre of the Syrian Society against Cancer, Aleppo, Syria; 5Nova Scotia Community College, Dartmouth, NS, 6École de Technologie Supérieure, Montreal, QC, Canada; 7Department of Mechanical Engineering, Khalifa University, Abu Dhabi, UAE; 8Segal Cancer Centre, Lady Davis Institute for Medical Research of the Sir Mortimer B. Davis-Jewish General Hospital, Montreal, QC, Canada Abstract: Carbon nanotubes (CNTs) are considered one of the most interesting materials in the 21st century due to their unique physiochemical characteristics and applicability to various industrial products and medical applications. However, in the last few years, questions have been raised regarding the potential toxicity of CNTs to humans and the environment; it is believed that the physiochemical characteristics of these materials are key determinants of CNT interaction with living cells and hence determine their toxicity in humans and other organisms as well as their embryos. Thus, several recent studies, including ours, pointed out that CNTs have cytotoxic effects on human and animal cells, which occur via the alteration of key regulator genes of cell proliferation, apoptosis, survival, cell–cell adhesion, and angiogenesis. Meanwhile, few investigations revealed that CNTs could also be harmful to the normal development of the embryo. In this review, we will discuss the toxic role of single-walled CNTs in the embryo, which was recently explored by several groups including ours. Keywords: single-walled carbon nanotubes, embryo, toxicity

Introduction: Cervical cancer is among the most common types of cancer in women and is associated with human papillomavirus (HPV) infection. The association between cervical cancer and high-risk HPV infection has been well documented. However, the effect of simultaneous infection with high- and low-risk HPV or low-risk HPV alone on the risk of developing cervical malignancy remains unanswered in guidelines., Method: We investigated the association of high and low-risk HPVs (HR or LR) genotypes with cervical carcinoma risk and pathological and cytological information in cases recruited from a population-based cohort study of 790 patients. Correlation matrix and t-test were used for analysis., Results: The percentage of HR+LR and HR-HPV16/18 were 9.30% and 11.20% in class II, 7.15% and 7.10% in class IV, and 7.15% and 5.80% in As-CUS smears. Interestingly, concurrent infection with HR-HPV and LR-HPV types led to a significant reduction in the risk of developing malignancy compared to the high-risk group (OR=0.3 (0.098-0.925), pvalue=0.04). The percentage of individuals with cervical malignancy was 10.2% and 28.2% within the co-infected and the HR-HPV participants., Conclusion: Our findings suggest that simultaneous infection with high- and low-risk HPV may reduce the risk of cervical malignancy., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Pancreatic ductal adenocarcinoma (PDAC) is currently the fourth leading cause of death in the United States and is expected to be ranked second in the next 10 years due to poor prognosis and a rising incidence. Distant metastatic PDAC is associated with the worst prognosis among the different phases of PDAC. The diagnostic options for PDAC are convenient and available for staging, tumor response evaluation, and management of resectable or borderline resectable PDAC. However, imaging is crucial in PDAC diagnosis, monitoring, resectability appraisal, and response evaluation. The advancement of medical technologies is evolving, hence the use of imaging in PDAC treatment options has grown as well as the utilization of ctDNA as a tumor marker. Treatment options for metastatic PDAC are minimal with the primary goal of therapy limited to symptom relief or palliation, especially in patients with low functional capacity at the point of diagnosis. Molecular profiling has shown promising potential solutions that would push the treatment boundaries for patients with PDAC. In this review, we will discuss the latest updates from evidence-based guidelines regarding diagnosis, therapy response evaluation, prognosis, and surveillance, as well as illustrating novel therapies that have been recently investigated for PDAC, in addition to discussing the molecular profiling advances in PDAC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Bugazia, Al-Najjar, Esmail, Abdelrahim, Abboud, Abdelrahim, Umoru, Rayyan, Abudayyeh, Al Moustafa and Abdelrahim.)

Angiogenesis is the process of forming new blood capillaries from pre-existing vessels. Even though it is essential during normal development, it plays a major role in cancer progression. Neratinib is a pan-human epidermal growth factor receptor (HER) inhibitor that has recently been approved for the treatment of HER2-positive breast cancer. However, its effects on angiogenesis and embryogenesis remain unknown. This study examined the antiangiogenic effects of neratinib using the chorioallantoic membrane (CAM) of chicken embryos. We also evaluated neratinib's toxicity during the early stages of normal development using the chicken embryos, primary embryonic fibroblasts (EFBs), and human umbilical vein endothelial cells (HUVEC). Our findings revealed that neratinib significantly inhibited the CAM angiogenesis compared to controls by reducing vessel percentage area and the average vessel length. Furthermore, neratinib downregulated vascular endothelial growth factor (VEGF), a key mediator of angiogenesis. At lower concentrations, neratinib was well-tolerated during early stages of normal development. Additionally, EFBs treated with neratinib showed no morphological or viability changes when compared to controls. However, at the highest concentration tested, neratinib treatment reduced HUVEC cell viability. This effect may be associated with the dysregulation of key apoptotic genes, including caspase-3, caspase-8, caspase-9, and the B-cell lymphoma 2 (Bcl2) gene. Our findings indicate a novel potential application of neratinib as an antiangiogenic agent, exhibiting tolerable toxicity in the early stages of embryogenesis.

Background: Recent investigations have reported the benefits of using a tyrosine kinase inhibitor, dasatinib (DA), as well as programmed death-ligand 1 (PD-L1) inhibitors in the management of several solid tumors, including breast cancer. Nevertheless, the outcome of the combination of these inhibitors on HER2-positive breast cancer is not explored yet., Methods: Herein, we investigated the impact of DA and PD-L1 inhibitor (BMS-202) combination on HER2-positive breast cancer cell lines, SKBR3 and ZR75., Results: Our data reveal that the combination significantly inhibits cell viability of both cancer cell lines as compared to monotreatment. Moreover, the combination inhibits epithelial-mesenchymal transition (EMT) progression and reduces cancer cell invasion by restoring E-cadherin and β-catenin expressions and loss of vimentin, major biomarkers of EMT. Additionally, the combination reduces the colony formation of both cell lines in comparison with their matched control. Also, the combination considerably inhibits the angiogenesis of the chorioallantoic membrane model compared with monotreatment. Molecular pathway analysis of treated cells shows that this combination blocks HER2, AKT, β-catenin, and JNK1/2/3 activities., Conclusion: Our findings implicate that a combination of DA and BMS-202 could have a significant impact on the management of HER2-positive breast cancer., (© 2024. The Author(s).)

Gastric cancer, a multifactorial disease, is considered one of the most common malignancies worldwide. In addition to genetic and environmental risk factors, infectious agents, such as Epstein-Barr virus (EBV) and Helicobacter pylori ( H.pylori ) contribute to the onset and development of gastric cancer. H. pylori is a type I carcinogen that colonizes the gastric epithelium of approximately 50% of the world's population, thus increasing the risk of gastric cancer development. On the other hand, epithelial mesenchymal transition (EMT) is a fundamental process crucial to embryogenic growth, wound healing, organ fibrosis and cancer progression. Several studies associate gastric pathogen infection of the epithelium with EMT initiation, provoking cancer metastasis in the gastric mucosa through various molecular signaling pathways. Additionally, EMT is implicated in the progression and development of H. pylori -associated gastric cancer. In this review, we recapitulate recent findings elucidating the association between H. pylori infection in EMT promotion leading to gastric cancer progression and metastasis., Competing Interests: “The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results”., (© 2023 The Author(s).)

High-risk human papillomaviruses (HPVs) are considered risk factors in the origin of several human malignancies, such as breast, cervical, head and neck, as well as colorectal cancers. However, there are no data reported on the HPV status in colorectal cancer in the State of Qatar. Therefore, we herein examined the presence of high-risk HPVs (16, 18, 31, 33, 35, 45, 51, 52, and 59), using polymerase chain reaction (PCR) in a cohort of 100 Qatari colorectal cancer patients, and their association with tumor phenotype. We found that high-risk HPV types 16, 18, 31, 35, 45, 51, 52, and 59 were present in 4, 36, 14, 5, 14, 6, 41, and 17% of our samples, respectively. Overall, 69 (69%) of the 100 samples were HPV positive; among these, 34/100 (34%) were positive for single HPV subtypes, while 35/100 (35%) of the samples were positive for two or more HPV subtypes. No significant association was noted between the presence of HPV and tumor grade, stage, or location. However, the presence of coinfection of HPV subtypes strongly correlated with advanced stage (stage 3 and 4) colorectal cancer, indicating that the copresence of more than one HPV subtype can significantly worsen the prognosis of colorectal cancer. The results from this study imply that coinfection with high-risk HPV subtypes is associated with the development of colorectal cancer in the Qatari population.

Introduction: Immune checkpoint blockade (ICB)-based therapy is revolutionizing cancer treatment by fostering successful immune surveillance and effector cell responses against various types of cancers. However, patients with HER2+ cancers are yet to benefit from this therapeutic strategy. Precisely, several questions regarding the right combination of drugs, drug modality, and effective dose recommendations pertaining to the use of ICB-based therapy for HER2+ patients remain unanswered., Methods: In this study, we use a mathematical modeling-based approach to quantify the growth inhibition of HER2+ breast cancer (BC) cell colonies (ZR75) when treated with anti-HER2; trastuzumab (TZ) and anti-PD-1/PD-L1 (BMS-202) agents., Results and Discussion: Our data show that a combination therapy of TZ and BMS-202 can significantly reduce the viability of ZR75 cells and trigger several morphological changes. The combination decreased the cell's invasiveness along with altering several key pathways, such as Akt/mTor and ErbB2 compared to monotherapy. In addition, BMS-202 causes dose-dependent growth inhibition of HER2+ BC cell colonies alone, while this effect is significantly improved when used in combination with TZ. Based on the in-vitro monoculture experiments conducted, we argue that BMS-202 can cause tumor growth suppression not only by mediating immune response but also by interfering with the growth signaling pathways of HER2+BC. Nevertheless, further studies are imperative to substantiate this argument and to uncover the potential crosstalk between PD-1/PD-L1 inhibitors and HER2 growth signaling pathways in breast cancer., Competing Interests: Author AH was employed by Hamad Medical Corporation. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Padmanabhan, Kheraldine, Gupta, Meskin, Hamad, Vranic and Al Moustafa.)

The human papillomavirus (HPV) is a non-enveloped double-stranded DNA virus capable of infecting skin and mucosa epithelial cells. Commonly, HPV infection is associated with sexually transmitted diseases and is considered the leading cause of cervical cancer and other carcinomas of the anogenital tract. However, several studies reported their involvement in cancers of non-sexual regions, including colorectal, head and neck, and breast cancers. There are several studies from the Middle East and North Africa (MENA) regions on the potential association between high-risk HPVs and cancer; nevertheless, there are limited studies that address the significance of HPV vaccination as a potential guard against these cancers. In the current review, we present a comprehensive description of the current HPV-associated cancers prevalence rates in the MENA region, demonstrating their steady increase with time, especially in African regions. Moreover, we discuss the potential impact of vaccination against HPV infections and its outcome on human health in this region.

Background: nanotechnology is one of the fastest-growing areas, and it is expected to have a substantial economic and social impact in the upcoming years. Gold particles (AuNPs) offer an opportunity for wide-ranging applications in diverse fields such as biomedicine, catalysis, and electronics, making them the focus of great attention and in parallel necessitating a thorough evaluation of their risk for humans and ecosystems. Accordingly, this study aims to evaluate the acute and developmental toxicity of surface-modified gold nanorods (AuNRs), on zebrafish ( Danio rerio ) early life stages., Methods: in this study, zebrafish embryos were exposed to surface-modified AuNRs at concentrations ranging from 1 to 20 μg/mL. Lethality and developmental endpoints such as hatching, tail flicking, and developmental delays were assessed until 96 h post-fertilization (hpf)., Results: we found that AuNR treatment decreases the survival rate in embryos in a dose-dependent manner. Our data showed that AuNRs caused mortality with a calculated LC50 of EC 50,24hpf of AuNRs being 9.1 μg/mL, while a higher concentration of AuNRs was revealed to elicit developmental abnormalities. Moreover, exposure to high concentrations of the nanorods significantly decreased locomotion compared to untreated embryos and caused a decrease in all tested parameters for cardiac output and blood flow analyses, leading to significantly elevated expression levels of cardiac failure markers ANP / NPPA and BNP / NPPB ., Conclusions: our results revealed that AuNR treatment at the EC 50 induces apoptosis significantly through the P53 , BAX / BCL-2 , and CASPASE pathways as a suggested mechanism of action and toxicity modality., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Advancement in the development of molecular sequencing platforms has identified infectious bacteria or viruses that trigger the dysregulation of a set of genes inducing the epithelial-mesenchymal transition (EMT) event. EMT is essential for embryogenesis, wound repair, and organ development; meanwhile, during carcinogenesis, initiation of the EMT can promote cancer progression and metastasis. Recent studies have reported that interactions between the host and dysbiotic microbiota in different tissues and organs, such as the oral and nasal cavities, esophagus, stomach, gut, skin, and the reproductive tract, may provoke EMT. On the other hand, it is revealed that certain microorganisms display a protective role against cancer growth, indicative of possible therapeutic function. In this review, we summarize recent findings elucidating the underlying mechanisms of pathogenic microorganisms, especially the microbiota, in eliciting crucial regulator genes that induce EMT. Such an approach may help explain cancer progression and pave the way for developing novel preventive and therapeutic strategies.

Breast cancer (BC) is the most common malignant cancer in females worldwide. Drug resistance, toxicity, and the failure of current therapies to completely cure BC has challenged conventional medicine. Consequently, complementary alternative medicine has become popular due to its safety and efficacy. Haematococcus pluvialis ( H. pulvialis ) is a green microalga living in fresh water, and its crude extract is rich of bioactives, including carotenoids, known to inhibit cancer cell growth. In the present study, we investigated the effects of a methanol crude extract called "T1" of H. pulvialis on cell growth and migration/invasion of the BC cell line MDA-MB-231 in comparison to the fibroblast control cells. TI significantly suppressed BC cell growth, inhibited migration and invasion and induced apoptosis. Interestingly, apoptosis was mediated by a significant loss of mutant p53 protein, and increased Bax/Bcl2 ratio. Our findings support our hypothesis that T1 exerts its anti-cancer effects by inhibiting BC invasion and inducing apoptosis mediated, at least, via the p53/Bax/Bcl2 pathway. Ongoing experiments aim to identify the molecular mechanisms underpinning T1-inhibited BC cell invasion using pre-designed metastasis gene-based array method., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Alateyah, Ahmad, Gupta, Fouzat, Thaher, Das, Al Moustafa and Ouhtit.)

Elaeagnus angustifolia ( EA ) is used as an alternative medicine in the Middle East to manage numerous human diseases. We recently reported that EA flower extract inhibits cell proliferation and invasion of human oral and HER2-positive breast cancer cells. Nevertheless, the outcome of EA extract on triple-negative breast cancer (TNBC) cells has not been explored yet. We herein investigate the effect of the aqueous EA extract (100 and 200 μl/ml) on two TNBC cell lines (MDA-MB-231 and MDA-MB-436) for 48 h and explore its underlying molecular pathways. Our data revealed that EA extract suppresses cell proliferation by approximately 50% and alters cell-cycle progression of these two cancer cell lines. Additionally, EA extract induces cell apoptosis by 40-50%, accompanied by the upregulation of pro-apoptotic markers (Bax and cleaved caspase-8) and downregulation of the anti-apoptotic marker, Bcl-2. Moreover, EA extract inhibits colony formation compared to their matched control. More significantly, the molecular pathway analysis of EA -treated cells revealed that EA extract enhances p53 expression, while inhibiting the expression of total and phosphorylated Signal Transducer and Activator Of Transcription 3 (STAT3) in both cell lines, suggesting p53 and STAT3 are the main key players behind the biological events provoked by the extract in TNBC cells. Our findings implicate that EA flower extract may possess an important potential as an anticancer drug against TNBC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Fouzat, Hussein, Gupta, Al-Farsi, Khalil and Al Moustafa.)

Introduction: Over the past decade obesity prevalence has been increasing rapidly in the Gulf region (GR) including Qatar, becoming one of the major health issues in the region. Concomitantly, waterpipe (WP) smoking is increasing worldwide especially in the GR, and although the effect of cigarette smoking on body weight is well-established, studies indicating an association between WP smoking and obesity are scarce. Thus, we explored the association between WP smoking and obesity in comparison with cigarette smokers and healthy population in Qatar., Methods: We performed a cross-sectional study using data from Qatar Biobank and analyzed anthropometric measurements among 879 adults (aged 18-65 years) that included WP smokers, cigarette smokers, dual smokers and never smokers. Body composition was measured using bioelectrical impedance analysis and reported as lean mass, fat mass, and body fat percentage., Results: Overall, 12% (n=108) were WP smokers, 22% (n=196) were cigarette smokers, 9% (n=77) smoked both WP and cigarettes and 57% (n=498) were never smokers. Age, sex, history of diabetes, and hypertension, in addition to nationality were considered as confounding factors. Our analysis revealed that WP smokers had a significantly higher BMI (kg/m 2 ) and fat mass when compared with cigarette smokers (p<0.05). Moreover, compared to cigarette smoking, WP smoking had a higher significant effect on BMI (β=3.8, SE=0.38; and β=5.5, SE=0.46; respectively), and fat mass (β=5.1, SE=0.79; and β=9.0, SE=0.97; respectively). However, WP users were similar to never-smokers in terms of body fat percent., Conclusions: Our data indicate that compared to never smokers, daily WP users have higher BMI and fat mass, and are likely to be obese., Competing Interests: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none was reported., (© 2022 Alkeilani A.A. et al.)

Introduction: Human papillomaviruses (HPVs), Epstein-Barr virus (EBV), and mouse mammary tumor virus-like virus (MMTV-like virus) can be present and contribute to breast cancer development and progression. However, the role of these oncoviruses and their crosstalk in breast cancer is still unclear., Methods: We explored the co-presence of high-risk HPVs, EBV, and MMTV-like virus in 74 breast cancer samples from Qatar using PCR., Results: We found the presence of HPV and EBV in 65% and 49% of our cancer sample cohorts; 47% of the samples are positive for both oncoviruses. The MMTV-like virus alone was detected in 15% of the samples with no significant association with clinicopathological features. The three oncoviruses were co-present in 14% of the cases; no significant association was noted between the co-presence of these viruses and the clinicopathological features., Conclusion: Despite the presence of the oncoviruses, additional studies are necessary to understand their interactions in human breast carcinogenesis., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Recurrent Respiratory Papillomatosis (RRP) is a rare but severe manifestation of human papillomavirus (HPV). As our knowledge about HPV infections has expanded, it has become possible to understand the course of RRP disease and unravel plausible efficient methods to manage the disease. However, the surge in reports on HPV has not been accompanied by a similar increase in research about RRP specifically. In this paper, we review the clinical manifestation and typical presentation of the illness. In addition, the pathogenesis and progression of the disease are described. On the other hand, we discuss the types of treatments currently available and future treatment strategies. The role of vaccination in both the prevention and treatment of RRP will also be reviewed. We believe this review is essential to update the general knowledge on RRP with the latest information available to date to enhance our understanding of RRP and its management.

Fascin is an actin-binding protein that is encoded by the FSCN1 gene (located on chromosome 7). It triggers membrane projections and stimulates cell motility in cancer cells. Fascin overexpression has been described in different types of human cancers in which its expression correlated with tumor growth, migration, invasion, and metastasis. Moreover, overexpression of fascin was found in oncovirus-infected cells, such as human papillomaviruses (HPVs) and Epstein-Barr virus (EBV), disrupting the cell-cell adhesion and enhancing cancer progression. Based on these findings, several studies reported fascin as a potential biomarker and a therapeutic target in various cancers. This review provides a brief overview of the FSCN1 role in various cancers with emphasis on gynecological malignancies. We also discuss fascin interactions with other genes and oncoviruses through which it might induce cancer development and progression.

Breast cancer, the most frequent disease amongst women worldwide, accounts for the highest cancer-related mortality rate. Triple-negative breast cancer (TNBC) subtype encompasses ~15% of all breast cancers and lack estrogen, progesterone, and HER2 receptors. Although risk factors for breast cancer are well-known, factors underpinning breast cancer onset and progression remain unknown. Recent studies suggest the plausible role of oncoviruses including human papillomaviruses (HPVs), Epstein-Barr virus (EBV), and mouse mammary tumor virus (MMTV) in breast cancer pathogenesis. However, the role of these oncoviruses in TNBC is still unclear. In the current study, we explored the status of high-risk HPVs, EBV, and MMTV in a well-defined TNBC cohort from Croatia in comparison to 16 normal/non TNBC samples (controls) using polymerase chain reaction assay. We found high-risk HPVs and EBV present in 37/70 (53%) and 25/70 (36%) of the cases, respectively. The most common HPV types are 52, 45, 31, 58 and 68. We found 16% of the samples positive for co-presence of high-risk HPVs and EBV. Moreover, our data revealed that 5/70 (7%) samples are positive for MMTV. In addition, only 2/70 (3%) samples had co-presence of HPVs, EBV, and MMTV without any significant association with the clinicopathological variables. While, 6/16 (37.5%) controls were positive for HPV ( p = .4), EBV was absent in all controls (0/16, 0%) ( p = .01). In addition, we did not find the co-presence of the oncoviruses in the controls ( p > .05). Nevertheless, further investigations are essential to understand the underlying mechanisms of multiple-oncogenic viruses' interaction in breast carcinogenesis, especially TNBC.

Since the discovery and fabrication of carbon nanofibers (CNFs) over a decade ago, scientists foster to discover novel myriad potential applications for this material in both biomedicine and industry. The unique economic viability, mechanical, electrical, optical, thermal, and structural properties of CNFs led to their rapid emergence. CNFs become an artificial intelligence platform for different uses, including a wide range of biomedical applications. Furthermore, CNFs have exceptionally large surface areas that make them flexible for tailoring and functionalization on demand. This review highlights the recent progress and achievements of CNFs in a wide range of biomedical fields, including cancer therapy, biosensing, tissue engineering, and wound dressing. Besides the synthetic techniques of CNFs, their potential toxicity and limitations, as biomaterials in real clinical settings, will be presented. This review discusses CNF's future investigations in other biomedical fields, including gene delivery and bioimaging and CNFs risk assessment., (© 2021 Wiley Periodicals LLC.)

Drug delivery systems or vectors are usually needed to improve the bioavailability and effectiveness of a drug through improving its pharmacokinetics/pharmacodynamics at an organ, tissue or cellular level. However, emerging technologies with sensitive readouts as well as a greater understanding of physiological/biological systems have revealed that polymeric drug delivery systems are not biologically inert but can have innate or intrinsic biological actions. In this article, we review the emerging multiple innate biological/toxicological properties of naked polyamidoamine (PAMAM) dendrimer delivery systems in the absence of any drug cargo and discuss their correlation with the defined physicochemical properties of PAMAMs in terms of molecular size (generation), architecture, surface charge and chemistry. Further, we assess whether any of the reported intrinsic biological actions of PAMAMs such as their antimicrobial activity or their ability to sequester glucose and modulate key protein interactions or cell signaling pathways, can be exploited clinically such as in the treatment of diabetes and its complications., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Gold nanorods have been implicated in several biomedical applications. Herein, the effect of two surface-modified gold nanorods on the early stages of embryogenesis and angiogenesis was investigated using avian embryos at three days and their chorioallantoic membrane (CAM) at five days of incubation. We found that gold nanorods (GNR) modified with PEGylated phospholipid moiety show a high mortality rate in embryos after four days of exposure compared to GNR modified with PEGylated cholesterol moiety. Meanwhile, our data revealed that surface modified-GNR significantly inhibit the formation of new blood vessels in the treated CAM model after 48 h of exposure. Moreover, we report that surface-modified GNR significantly deregulate the expression of several genes implicated in cell proliferation, invasion, apoptosis, cellular energy metabolism, and angiogenesis. On the other hand, our data point out that GNR treatments can modulate the expression patterns of JNK1/2/3, NF-KB/p38, and MAPK, which could be the main molecular pathways of the nanorods in our experimental models.

Background: High-risk human papillomaviruses (HPVs) are present and can cooperate with Epstein-Barr virus (EBV) to initiate and/or enhance the progression of several types of human carcinomas including cervical as well as head and neck; in parallel, it has been recently pointed out that these oncoviruses can be detected in human breast cancers. Thus, we herein explored the presence/co-presence of high-risk HPVs and EBV in breast cancer in Lebanese women., Methods: A cohort of 102 breast cancer samples and 14 normal breast tissues were assessed for the presence of HPVs and EBV. Polymerase chain reaction (PCR) and immunohistochemistry (IHC) analysis in addition to tissue microarray (TMA) platform were used in this study., Results: We found the presence of HPV in 66/102 (65%) of our samples, while EBV is present in 41/102 (40%) of the cohort. Additionally, our data showed that high-risk HPV types (52, 35, 58, 45, 16 and 51) are the most frequent in breast cancer in Lebanese women. Meanwhile, we report that high-risk HPVs and EBV are co-present in 30/102 (29%) of the samples; more significantly, our results indicate that their co-presence is associated with tumor grade (p = 0.03)., Conclusion: Our data revealed that HPVs and EBV are present/co-present in human breast cancer where they may play an important role in its development and/or progression; thus, we believe that further investigations are essential to confirm and elucidate the presence/co-presence of these oncoviruses and the underlying mechanisms of their interaction in breast carcinogenesis.

HER2-positive breast cancer is one of its most challenging subtypes, forming around 15-25% of the total cases. It is characterized by aggressive behavior and treatment resistance. On the other hand, poly (amidoamine) (PAMAM) dendrimers are widely used in drug delivery systems and gene transfection as carriers. PAMAMs can modulate gene expression and interfere with transactivation of the human epidermal growth factor receptor family members (HER1-4). Nevertheless, the outcome of PAMAMs on HER2-positive breast cancer remains unknown. Thus, in this study, we investigated the anti-cancer effects of different generations of PAMAM dendrimers (G 4 and G 6 ) and the outcome of their surface chemistries (cationic, neutral, and anionic) on HER2-positive breast cancer cell lines, SKBR3 and ZR75. Our data showed that PAMAM dendrimers, mainly cationic types, significantly reduce cell viability in a dose-dependent manner. More significantly, PAMAMs induce substantial cell apoptosis, accompanied by the up-regulation of apoptotic markers (Bax, Caspases-3, 8 and 9) in addition to down-regulation of Bcl-2. Moreover, our data pointed out that cationic PAMAMs inhibit colony formation compared to controls and other types of PAMAMs. The molecular pathway analysis of PAMAM exposed cells revealed that PAMAMs enhance JNK1/2/3 expression while blocking ERK1/2, in addition to EGFR1 (HER1) and HER2 activities, which could be the major molecular pathway behind these events. These observed effects were comparable to lapatinib treatment, a clinically used inhibitor of HER1 and 2 receptors phosphorylation. Our findings implicate that PAMAMs may possess important therapeutic effects against HER2-positive breast cancer via JNK1/2/3, ERK1/2, and HER1/2 signalling pathways., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors.)

High-risk human papillomaviruses (HPV) can be present and cooperate with Epstein-Barr virus (EBV) to promote the onset and/or progression of various cancers including cervical, breast, head and neck as well as colorectal. In this investigation, we explored the co-prevalence of high-risk HPV and EBV in 74 breast cancer tissues from Qatari women using polymerase chain reaction. We found that high-risk HPV and EBV are present in 48/74 (65%) and 36/74 (49%) of the cases, respectively. While we noted that the presence of HPV presence is associated with triple-negative breast cancer (TNBC) ( p = .008), however, the presence of EBV did not correlate with any breast cancer subgroup. Moreover, our data revealed that high-risk HPV and EBV are co-present in 35/74 (47%) of the samples and their co-presence is significantly associated with tumor grade ( p = .04) and tumor stage ( p = .04). These data indicate that HPV and EBV are commonly co-present in breast cancer and their association could be linked with a more aggressive tumor phenotype. Thus, further investigations are essential to understand the underlying mechanisms of HPV and EBV cooperation in breast carcinogenesis.

Breast cancer is one of the leading causes of brain metastasis. Metastasis to the brain occurs if cancer cells manage to traverse the 'blood-brain barrier' (BBB), which is a barrier with a very tight junction (TJ) of endothelial cells between blood circulation and brain tissue. It is highly important to develop novel in vitro BBB models to investigate breast cancer metastasis to the brain to facilitate the screening of chemotherapeutic agents against it. We herein report the development of gelatin methacryloyl (GelMA) modified transwell insert based BBB model composed of endothelial and astrocyte cell layers for testing the efficacy of anti-metastatic agents against breast cancer metastasis to the brain. We characterized the developed model for the morphology and in vitro breast cancer cell migration. Furthermore, we investigated the effect of cisplatin, a widely used chemotherapeutic agent, on the migration of metastatic breast cancer cells using the model. Our results showed that breast cancer cells migrate across the developed BBB model. Cisplatin treatment inhibited the migration of cancer cells across the model. Findings of this study suggest that our BBB model can be used as a suitable tool to investigate breast cancer-associated brain metastasis and to identify suitable therapeutic agents against this.

Some viral outbreaks have plagued the world since antiquity, including the most recent COVID-19 pandemic. The continuous spread and emergence of new viral diseases have urged the discovery of novel treatment options that can overcome the limitations of currently marketed antiviral drugs. Chalcones are natural open chain flavonoids that are found in various plants and can be synthesised in labs. Several studies have shown that these small organic molecules exert a number of pharmacological activities, including antiviral, anti-inflammatory, antimicrobial and anticancer. The purpose of this review is to provide a summary of the antiviral activities of chalcones and their derivatives on a set of human viral infections and their potential for targeting the most recent COVID-19 disease. Accordingly, we herein review chalcones activities on the following human viruses: Middle East respiratory syndrome coronavirus, severe acute respiratory syndrome coronavirus, human immunodeficiency, influenza, human rhinovirus, herpes simplex, dengue, human cytomegalovirus, hepatitis B and C, Rift Valley fever and Venezuelan equine encephalitis. We hope that this review will pave the way for the design and development of potentially potent and broad-spectrum chalcone based antiviral drugs.

Breast cancer is a leading cause of death in women around the world. Most breast cancer-related deaths are a result of complications from the metastatic spread. Several recent studies reported that high-risk human papillomaviruses (HPVs) and Epstein-Barr virus (EBV) are co-presented in different types of human carcinomas including breast; however, the cooperative effects between high-risk HPVs and EBV oncoproteins in human breast cancer have not been investigated yet. Thus, we herein explored the cooperation outcome between E6/E7 and latent membrane protein 1 (LMP1) oncoproteins of high-risk HPV type 16 and EBV, respectively, in two human breast cancer cell lines, MCF7 and MDA-MB-231. Our data revealed that the cooperation of E6/E7 and LMP1 oncoproteins stimulates cell proliferation and deregulates cell cycle progression of human breast cancer and normal mammary cells; in parallel, we noted that E6/E7/LMP1 incite colony formation of both breast cancer cell lines but not normal cells. More significantly, our results point out that the co-expression of E6/E7 and LMP1 oncoproteins enhances cell motility and invasion of MCF7 and MDA-MB-231 cell lines; this is accompanied by deregulation of epithelial-mesenchymal transition biomarkers including E-cadherin, β-catenin, fascin, and vimentin. The molecular pathway analysis of HPV and EBV oncoproteins cooperation shows that it can enhance the phosphorylation of extracellular signal-regulated kinases (Erk1/Erk2) in addition to β-catenin, which could be behind the effect of this cooperation in our cell models. The study clearly suggests that high-risk HPV and EBV coinfection can play an important role in breast cancer progression via Erk1/Erk2 and β-catenin signaling pathways., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Gupta, Jabeen, Vranic, Al Moustafa and Al-Thawadi.)

Carbon nanofibers (CNFs) have been implicated in biomedical applications, yet, they are still considered as a potential hazard. Conversely, mesoporous silica is a biocompatible compound that has been used in various biomedical applications. In this regard, we recently reported that CNFs induce significant toxicity on the early stage of embryogenesis in addition to the inhibition of its angiogenesis. Thus, we herein use mesoporous silica coating of CNFs (MCNFs) in order to explore their outcome on normal development and angiogenesis using avian embryos at 3 days and its chorioallantoic membrane (CAM) at 6 days of incubation. Our data show that mesoporous silica coating of CNFs significantly reduces embryotoxicity provoked by CNFs. However, MCNFs exhibit slight increase in angiogenesis inhibition in comparison with CNFs. Further investigation revealed that MCNFs slightly deregulate the expression patterns of key controller genes involved in cell proliferation, survival, angiogenesis, and apoptosis as compared to CNFs. We confirmed these data using avian primary normal embryonic fibroblast cells established in our lab. Regarding the molecular pathways, we found that MCNFs downregulate the expression of ERK1/ERK2, p-ERK1/ERK2 and JNK1/JNK2/JNK3, thus indicating a protective role of MCNFs via ERK and JNK pathways. Our data suggest that coating CNFs with a layer of mesoporous silica can overcome their toxicity making them suitable for use in biomedical applications. Nevertheless, further investigations are required to evaluate the effects of MCNFs and their mechanisms using different in vitro and in vivo models., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Dasatinib is a targeted cancer therapy, while programmed death ligand 1 (PD-L1) inhibitors are a form of immune checkpoint therapy used to treat various types of cancers. Several studies showed the potential efficacy of these drugs in the management of triple-negative breast cancer- an aggressive subtype of breast cancer, which can develop during pregnancy. Nevertheless, side effects of Dasatinib (DA) and PD-L1 drugs during pregnancy, especially in the early stages of embryogenesis are not explored yet. The aim of this study is to assess the individual and combined toxicity of DA and PD-L1 inhibitors during the early stages of embryogenesis and to evaluate their effect(s) on angiogenesis using the chorioallantoic membrane (CAM) model of the embryo. Our results show that embryos die at greater rates after exposure to DA and PD-L1 inhibitors as compared to their matched controls. Moreover, treatment with these drugs significantly inhibits angiogenesis of the CAM. To further elucidate key regulator genes of embryotoxicity induced by the actions of PD-L1 and DA, an RT-PCR analysis was performed for seven target genes that regulate cell proliferation, angiogenesis, and survival (ATF3, FOXA2, MAPRE2, RIPK1, INHBA, SERPINA4, and VEGFC). Our data revealed that these genes are significantly deregulated in the brain, heart, and liver tissues of exposed embryos, compared to matched control tissues. Nevertheless, further studies are necessary to evaluate the effects of these anti breast cancer drugs and elucidate their role during pregnancy., (Copyright © 2020 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Management of chronic diabetic ulcers remains as a major challenge in healthcare which requires extensive multidisciplinary approaches to ensure wound protection, management of excess wound exudates and promoting healing. Developing wound healing patches that can act as a protective barrier and support healing is highly needed to manage chronic diabetic ulcers. In order to boost the wound healing potential of patch material, bioactive agents such as growth factors can be used. Porous membranes made of nanofibers generated using electrospinning have potential for application as wound coverage matrices. However, electrospun membranes produced from several biodegradable polymers are hydrophobic and cannot manage the excess exudates produced by chronic wounds. Gelatin-methacryloyl (GelMA) hydrogels absorb excess exudates and provide an optimal biological environment for the healing wound. Epidermal growth factor (EGF) promotes cell migration, angiogenesis and overall wound healing. Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) membranes provide microbial, thermal and mechanical barrier properties to the wound healing patch. Herein, we developed a biodegradable polymeric patch based on the combination of mechanically stable electrospun PHBV, GelMA hydrogel and EGF for promoting diabetic wound healing. In vitro and in vivo studies were carried out to evaluate the effect of developed patches on cell proliferation, cell migration, angiogenesis and wound healing. Our results showed that EGF loaded patches can promote the migration and proliferation of multiple types of cells (keratinocytes, fibroblasts and endothelial cells) and enhance angiogenesis. In situ development of the patch and subsequent in vivo wound healing study in diabetic rats showed that EGF loaded patches provide rapid healing compared to control wounds. Interestingly, 100 ng EGF per cm 2 of the patches was enough to provide favourable cellular response, angiogenesis and rapid diabetic wound healing. Overall results indicate that EGF loaded PHBV-GelMA hybrid patch could be a promising approach to promote diabetic wound healing., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Susceptibility to severe illness from COVID-19 is anticipated to be associated with cigarette smoking as it aggravates the risk of cardiovascular and respiratory illness, including infections. This is particularly important with the advent of a new strain of coronaviruses, the severe acute respiratory syndrome coronavirus (SARS-CoV-2) that has led to the present pandemic, coronavirus disease 2019 (COVID-19). Although, the effects of smoking on COVID-19 are less described and controversial, we presume a link between smoking and COVID-19. Smoking has been shown to enhance the expression of the angiotensin-converting enzyme-2 ( ACE-2 ) and transmembrane serine protease 2 ( TMPRSS2 ) key entry genes utilized by SARS-CoV-2 to infect cells and induce a 'cytokine storm', which further increases the severity of COVID-19 clinical course. Nevertheless, the impact of smoking on ACE-2 and TMPRSS2 receptors expression remains paradoxical. Thus, further research is necessary to unravel the association between smoking and COVID-19 and to pursue the development of potential novel therapies that are able to constrain the morbidity and mortality provoked by this infectious disease. Herein we present a brief overview of the current knowledge on the correlation between smoking and the expression of SARS-CoV-2 key entry genes, clinical manifestations, and disease progression., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)

Colorectal cancer (CRC), the third most common type of cancer, is the second leading cause of cancer-related mortality rates worldwide. Although modern research was able to shed light on the pathogenesis of CRC and provide enhanced screening strategies, the prevalence of CRC is still on the rise. Studies showed several cellular signaling pathways dysregulated in CRC, leading to the onset of malignant phenotypes. Therefore, analyzing signaling pathways involved in CRC metastasis is necessary to elucidate the underlying mechanism of CRC progression and pharmacotherapy. This review focused on target genes as well as various cellular signaling pathways including Wnt/β-catenin, p53, TGF-β/SMAD, NF-κB, Notch, VEGF, and JAKs/STAT3, which are associated with CRC progression and metastasis. Additionally, alternations in methylation patterns in relation with signaling pathways involved in regulating various cellular mechanisms such as cell cycle, transcription, apoptosis, and angiogenesis as well as invasion and metastasis were also reviewed. To date, understanding the genomic and epigenomic instability has identified candidate biomarkers that are validated for routine clinical use in CRC management. Nevertheless, better understanding of the onset and progression of CRC can aid in the development of early detection molecular markers and risk stratification methods to improve the clinical care of CRC patients.

Breast and cervical cancers comprise 50% of all cancers during pregnancy. In particular, gestational breast cancer is considered one of the most aggressive types of cancers, which is a rare but fatal disease. However, the incidence of this type of cancer is increasing over the years and its prevalence is expected to rise further as more women delay childbearing. Breast cancer occurring after pregnancy is generally triple negative with specific characterizations of a poorer prognosis and outcome. On the other hand, it has been pointed out that this cancer is associated with a specific group of genes which can be used as precise targets to manage this deadly disease. Indeed, combination therapies consisting of gene-based agents with other cancer therapeutics is presently under consideration. We herein review recent progress in understanding the development of breast cancer during pregnancy and their unique subtype of triple negative which is the hallmark of this type of breast cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Allouch, Gupta, Malik, Al Farsi, Vranic and Al Moustafa.)

We recently performed two studies exploring the presence of Epstein-Barr virus (EBV) and high-risk human papillomaviruses (HPVs) types 16, 18, 31, 33 and 35 in human colorectal cancers from the Syrian population. Herein, we report that EBV and high-risk HPVs are co-present in colorectal cancers from Syria. We reveal that 17 (~17%) of 102 cancer samples are positive for both EBV and high-risk HPVs and their co-presence is associated with high/intermediate grade invasive carcinomas. These data suggest that EBV and high-risk HPVs are co-present in human colorectal cancers where they might cooperate on the initiation and/or progression of these cancers. Thus, we believe that future studies are necessary to confirm the co-presence of these oncoviruses and their cooperative role in human colorectal carcinogenesis.

To investigate the impact of poly(amidoamine) dendrimers (PAMAMs) in the embryo, we explored the outcome of different generations (G₄ and G 6 ) on the early stages of embryogenesis using the chicken embryo as a model. We also monitored their effect on angiogenesis in the chorioallantoic membrane (CAM). Our data revealed that cationic PAMAMs provoke substantial embryotoxicity, as they significantly induce death (up to 50%, p < 0 05) and inhibit angiogenesis of the CAM (up to 30%, p < 0 05) in a generation-dependent manner in comparison to controls and other types of PAMAMs (anionic and neutral). Moreover, cationic PAMAMs alter the expression of genes related to cell survival, cell cycle, proliferation, transcription factor, apoptosis, and angiogenesis, as shown by RT-PCR analysis. Our data suggest that PAMAM dendrimers exhibit intrinsic toxicity in embryos at the early stages and inhibits angiogenesis of the CAM. Thus, future studies are necessary to illustrate the exact mechanism of PAMAM dendrimers in embryotoxicity.

Water-pipe smoking (WPS) is becoming the most popular form of tobacco use among the youth, especially in the Middle East, replacing cigarettes rapidly and becoming a major risk of tobacco addiction worldwide. Smoke from WPS contains similar toxins as those present in cigarette smoke and is linked directly with different types of cancers including lung and head and neck (HN) carcinomas. However, the underlying molecular pathways and/or target genes responsible for the carcinogenic process are still unknown. In this study, human normal oral epithelial (HNOE) cells, NanoString PanCancer Pathways panel of 770 gene transcripts and quantitative real-time polymerase chain reaction (qRT-PCR) analysis were applied to discover differentially expressed genes (DEG) modulated by WPS. In silico analysis was performed to analyze the impact of these genes in HN cancer patient's biology and outcome. We found that WPS can induce the epithelial-mesenchymal transition (EMT: hallmark of cancer progression) of HNOE cells. More significantly, our analysis of NanoString revealed 23 genes deregulated under the effect of WPS, responsible for the modulation of cell cycle, proliferation, migration/invasion, apoptosis, signal transduction, and inflammatory response. Further analysis was performed using qRT-PCR of HNOE WPS-exposed and unexposed cells supported the reliability of our NanoString data. Moreover, we demonstrate those DEG to be upregulated in cancer compared with normal tissue. Using the Kaplan-Meier analysis, we observed a significant association between WPS-deregulated genes and relapse-free survival/overall survival in HN cancer patients. Our findings imply that WPS can modulate EMT as well as a set of genes that are directly involved in human HN carcinogenesis, thereby affecting HN cancer patients' survival.

Elaeagnus angustifolia ( EA ) is a medicinal plant used for treating several human diseases in the Middle East. Meanwhile, the outcome of EA extract on HER2-positive breast cancer remains nascent. Thus, we herein investigated the effects of the aqueous EA extract obtained from the flowers of EA on two HER2-positive breast cancer cell lines, SKBR3 and ZR75-1. Our data revealed that EA extract inhibits cell proliferation and deregulates cell-cycle progression of these two cancer cell lines. EA extract also prevents the progression of epithelial-mesenchymal transition (EMT), an important event for cancer invasion and metastasis; this is accompanied by upregulations of E-cadherin and β-catenin, in addition to downregulations of vimentin and fascin, which are major markers of EMT. Thus, EA extract causes a drastic decrease in cell invasion ability of SKBR3 and ZR75-1 cancer cells. Additionally, we found that EA extract inhibits colony formation of both cell lines in comparison with their matched control. The molecular pathway analysis of HER2 and JNK1/2/3 of EA extract exposed cells revealed that it can block HER2 and JNK1/2/3 activities, which could be the major molecular pathway behind these events. Our findings implicate that EA extract may possess chemo-preventive effects against HER2-positive breast cancer via HER2 inactivation and specifically JNK1/2/3 signaling pathways.

High-risk human papillomaviruses (high-risk HPVs) have been recently reported to be co-present with Epstein-Barr virus (EBV) in different types of human cancers including head and neck (HN), where they can cooperate in the initiation and/or progression of this cancer. Accordingly, we herein explored the prevalence of high-risk HPVs and EBV in 80 HN cancer tissues from the Syrian population using polymerase chain reaction, immunohistochemistry, and tissue microarray methodologies. We report that high-risk HPVs and EBV are present in 35/80 (43.7%) and 41/80 (51.2%) of our samples, respectively, and the most frequent HPV types are 33, 16, 18, 45, 52, 58, 35, 51, and 31, in this order. More significantly, our data reveal that 25/80 (31.2%) of cancer cases are positive for high-risk HPVs as well as EBV, and their co-presence is associated with high/intermediate-grade squamous cell carcinomas. These data confirm the co-presence of high-risk HPVs and EBV in HN cancers in the Syrian population of the Middle East and demonstrate that their co-incidence is linked to a more aggressive cancer phenotype. Thus, future studies are required to confirm these data and elucidate the exact role of high-risk and EBV cooperation in human HN carcinogenesis., (Copyright © 2020 Gupta, Ghabreau, Al-Thawadi, Yasmeen, Vranic, Al Moustafa and Malki.)

Human coronaviruses, especially SARS-CoV-2, are emerging pandemic infectious diseases with high morbidity and mortality in certain group of patients. In general, SARS-CoV-2 causes symptoms ranging from the common cold to severe conditions accompanied by lung injury, acute respiratory distress syndrome in addition to other organs' destruction. The main impact upon SARS-CoV-2 infection is damage to alveolar and acute respiratory failure. Thus, lung cancer patients are identified as a particularly high-risk group for SARS-CoV-2 infection and its complications. On the other hand, it has been reported that SARS-CoV-2 spike (S) protein binds to angiotensin-converting enzyme 2 (ACE-2), that promotes cellular entry of this virus in concert with host proteases, principally transmembrane serine protease 2 (TMPRSS2). Today, there are no vaccines and/or effective drugs against the SARS-CoV-2 coronavirus. Thus, manipulation of key entry genes of this virus especially in lung cancer patients could be one of the best approaches to manage SARS-CoV-2 infection in this group of patients. We herein provide a comprehensive and up-to-date overview of the role of ACE-2 and TMPRSS2 genes, as key entry elements as well as therapeutic targets for SARS-CoV-2 infection, which can help to better understand the applications and capacities of various remedial approaches for infected individuals, especially those with lung cancer.

Background: Human papillomaviruses (HPVs) and Epstein-Barr virus (EBV), known oncoviruses, can be co-present and cooperate in the initiation and/or progression of human carcinomas, including head and neck. Based on this fact, we recently reported the prevalence of both HPVs and EBV in cervical and breast cancers., Methods: We herein explore for the first time the co-prevalence of high-risk HPVs and EBV in 98 head and neck (HN) squamous cell carcinoma (SCC) tissues from Bosnian patients using polymerase chain reaction (PCR) and immunohistochemistry (IHC) analysis, as well as tissue microarray methodology., Results: The majority of these cancer tissue cases were from the oral cavity (68%). We found that high-risk HPVs and EBV are co-present in 34.7% of the SCC samples; with a significant correlation between the various HPV types and EBV co-incidence (p = 0.03). Our data showed that 30.8% of oral SCCs are positive for E6 oncoprotein of high-risk HPVs and 44.6% are positive for LMP1 of EBV. The most commonly expressed HPVs in our HNSCC samples include HPV types 16, 18, 45 and 58. Additionally, 37.5% of oral SCCs are positive for both HPVs and EBV, with statistically significant association between high-risk HPV types and EBV (p < 0.05). More importantly, our data revealed that the co-presence of HPV and EBV is strongly correlated with advanced tumor stage (p = 0.035)., Conclusion: In this study we show that HPV and EBV oncoviruses are co-present in HNSCC, particularly in oral cancer, where they can cooperate in the initiation and/or progression of this cancer. Thus, further studies are necessary to elucidate the mechanism of this cooperation., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2020.)

Cervical cancer is the fourth most common malignancy in women worldwide and a leading cause of cancer-related mortality in developing countries. Important etiological factors in this cancer are high-risk human papillomaviruses (HPV), as roughly 96% of cervical cancer cases are positive for these oncoviruses. On the other hand, it has been recently pointed out that E6/E7 oncoproteins of high-risk HPV can upregulate the programmed cell death-1/programmed cell death-ligand 1 (PD-1/PD-L1) axis. Likewise, several recent reports showed that checkpoint blockades targeting PD-1/PD-L1 pathways have achieved efficient clinical responses via suppressing cancer progression and improving survival in several types of human cancers including metastatic cervical cancer. In this review, we summarize recent advances in our understanding of the PD-1/PD-L1 signaling pathway and its interaction with high-risk HPV and their oncoproteins, which could have an important impact on the management of HPV-associated cancers including cervical., (Copyright © 2020 Allouch, Malki, Allouch, Gupta, Vranic and Al Moustafa.)

Colorectal cancer (CRC) is a common malignancy with a high mortality rate worldwide. It is a complex, multifactorial disease that is strongly impacted by both hereditary and environmental factors. The role of microbes (e.g., viruses) in the pathogenesis of CRC is poorly understood. In the current study, we explored the status of high-risk human papillomaviruses (HPV) and Epstein-Barr virus (EBV) in a well-defined CRC cohort using immunohistochemistry and polymerase chain reaction assays. Our data showed that high-risk HPVs were common (~80%) and EBV had a low presence (14-25%) in the CRC samples. The most common high-risk HPVs are HPV16, 31, 18, 51, 52 and 45 genotypes. The co-presence of high-risk HPV and EBV was observed in ~16% of the sample population without any significant association with the clinicopathological variables. We conclude that high-risk HPVs are very prevalent in CRC samples while EBV positivity is relatively low. The co-expression of the two viruses was observed in a minority of cases and without any correlation with the studied parameters. Further studies are necessary to confirm the clinical relevance and potential therapeutic (preventive) effects of the observations reported herein.

Implementation of carbon nanofibers (CNFs) in biomedical applications have successful outcomes, however, they are still considered as a potential hazard. We herein used avian embryos at 3 days and its chorioallantoic membrane (CAM) at 6 days of incubation to evaluate the impact of synthesized CNFs on the early stage of embryogenesis and angiogenesis. Our data point out that 50 μ g/embryo concentration of CNFs provoke adverse effects as 75% of CNFs-exposed embryos die within 1-5 days after exposure compared with their matched controls. Furthermore, CNFs significantly inhibit angiogenesis of the CAM after 48-hours post-treatment. Additionally, RT-PCR analysis on seven key controller genes responsible for proliferation, survival, angiogenesis, and apoptosis showed that these genes are deregulated in brain, heart, and liver tissues of CNFs-exposed embryos compared to their matched control. Our investigation suggests that CNFs could have a toxic effect on the early stages of embryogenesis as well as angiogenesis. Nevertheless, further investigations are required to evaluate the effects of CNFs and elucidate their mechanism on the early stage of the normal development and human health.

E-cigarette smoking (ECS) is a new method of tobacco smoking that is gaining popularity as it is thought to be a "healthy method" of tobacco consumption. The adverse outcomes of ECS on the respiratory and cardiovascular systems in humans have been recently demonstrated. Nevertheless, the effect of e-cigarette liquid (ECL) on the early stage of embryogenesis and angiogenesis has not been explored yet. Chicken embryo at 3 days of incubation and its chorioallantoic membrane (CAM) of 5 days were used to explore the outcome of ECL on the embryo. Real-time PCR was also employed to study the regulation of a set of key controller genes of embryogenesis as well as angiogenesis. Our study revealed that ECL exposure is associated with a high rate of mortality in embryos as around 70% of treated embryos, at 3 days of incubation, die after 5 days of exposure. Additionally, ECL inhibits angiogenesis of the CAM of 5 days of incubation by more than 30%. These effects could be explained by the upregulation of ATF-3, FOXA2, INHBA, MAPRE-2 , and RIPK-1, as well as the downregulation of SERPINA-4 and VEGF-C genes, which are important key controller genes of embryogenesis as well as angiogenesis. Our data suggest clearly that ECS can have dramatic toxic outcomes on the early stage of embryogenesis as well as angiogenesis. Accordingly, we believe that further studies to assess the effects of ECS on human health are essential.

DNA damage is well recognized as a critical factor in cancer development and progression. DNA lesions create an abnormal nucleotide or nucleotide fragment, causing a break in one or both chains of the DNA strand. When DNA damage occurs, the possibility of generated mutations increases. Genomic instability is one of the most important factors that lead to cancer development. DNA repair pathways perform the essential role of correcting the DNA lesions that occur from DNA damaging agents or carcinogens, thus maintaining genomic stability. Inefficient DNA repair is a critical driving force behind cancer establishment, progression and evolution. A thorough understanding of DNA repair mechanisms in cancer will allow for better therapeutic intervention. In this review we will discuss the relationship between DNA damage/repair mechanisms and cancer, and how we can target these pathways.

Human papillomaviruses (HPVs) and the Epstein-Barr virus (EBV) are the most common oncoviruses, contributing to approximately 10%-15% of all malignancies. Oncoproteins of high-risk HPVs (E5 and E6/E7), as well as EBV (LMP1, LMP2A and EBNA1), play a principal role in the onset and progression of several human carcinomas, including head and neck, cervical and colorectal. Oncoproteins of high-risk HPVs and EBV can cooperate to initiate and/or enhance epithelial-mesenchymal transition (EMT) events, which represents one of the hallmarks of cancer progression and metastasis. Although the role of these oncoviruses in several cancers is well established, their role in the pathogenesis of colorectal cancer is still nascent. This review presents an overview of the most recent advances related to the presence and role of high-risk HPVs and EBV in colorectal cancer, with an emphasis on their cooperation in colorectal carcinogenesis.

Breast cancer is one of the major causes of mortality in women worldwide. The most aggressive breast cancer subtypes are human epidermal growth factor receptor-positive (HER2 + ) and triple-negative breast cancers. Therapies targeting HER2 receptors have significantly improved HER2 + breast cancer patient outcomes. However, several recent studies have pointed out the deficiency of existing treatment protocols in combatting disease relapse and improving response rates to treatment. Overriding the inherent actions of the immune system to detect and annihilate cancer via the immune checkpoint pathways is one of the important hallmarks of cancer. Thus, restoration of these pathways by various means of immunomodulation has shown beneficial effects in the management of various types of cancers, including breast. We herein review the recent progress in the management of HER2 + breast cancer via HER2-targeted therapies, and its association with the programmed death receptor-1 (PD-1)/programmed death ligand-1 (PD-L1) axis. In order to link research in the areas of medicine and mathematics and point out specific opportunities for providing efficient theoretical analysis related to HER2 + breast cancer management, we also review mathematical models pertaining to the dynamics of HER2 + breast cancer and immune checkpoint inhibitors.