Nazia Nazam
@sites.uab.edu
Postdoctoral Fellow, Pediatric Surgery/Medicine
Dr. Elizabeth Beierle
RESEARCH, TEACHING, or OTHER INTERESTS
Cancer Research, Molecular Medicine, Molecular Biology, General Biochemistry, Genetics and Molecular Biology
Scopus Publications
Scholar Citations
Scholar h-index
Scholar i10-index
Scopus Publications
Janet R. Julson, Colin H. Quinn, Nazia Nazam, Laura V. Bownes, Jerry E. Stewart, and Elizabeth A. Beierle
Elsevier BV
Janet R. Julson, Colin H. Quinn, Swatika Butey, Michael H. Erwin, Raoud Marayati, Nazia Nazam, Jerry E. Stewart, and Elizabeth A. Beierle
MDPI AG
Hepatoblastoma is the most common primary pediatric liver tumor. Children with pulmonary metastases at diagnosis experience survival rates as low as 25%. We have shown PIM kinases play a role in hepatoblastoma tumorigenesis. In this study, we assessed the role of PIM kinases in metastatic hepatoblastoma. We employed the metastatic hepatoblastoma cell line, HLM_2. PIM kinase inhibition was attained using PIM3 siRNA and the pan-PIM inhibitor, AZD1208. Effects of PIM inhibition on proliferation were evaluated via growth curve. Flow cytometry determined changes in cell cycle. AlamarBlue assay assessed effects of PIM kinase inhibition and cisplatin treatment on viability. The lethal dose 50% (LD50) of each drug and combination indices (CI) were calculated and isobolograms constructed to determine synergy. PIM kinase inhibition resulted in decreased HLM_2 proliferation, likely through cell cycle arrest mediated by p21. Combination therapy with AZD1208 and cisplatin resulted in synergy, potentially through downregulation of the ataxia-telangiectasia mutated (ATM) kinase DNA damage response pathway. When assessing the combined effects of pharmacologic PIM kinase inhibition with cisplatin on HLM_2 cells, we found the agents to be synergistic, potentially through inhibition of the ATM pathway. These findings support further exploration of PIM kinase inhibition as a therapeutic strategy for metastatic hepatoblastoma.
Aisha Farhana, Abdullah Alsrhani, Nazia Nazam, Muhammad Ikram Ullah, Yusuf Saleem Khan, and Zafar Rasheed
MDPI AG
Objective: Breast cancer (BC) is the most common malignancy in females globally. Matrix metalloproteinase-9 (MMP-9) is crucial to the invasion, progression and spread of BC. Gold nanoparticles (AuNPs) have an anti-tumorigenic role, but their therapeutic role in microRNAs (miRNAs) regulation has not been explored. This study determined the potential of AuNPs against MMP-9 overexpression/production and miRNA-204-5p regulation in BC cells. Methods: AuNPs were newly engineered, and their stability was analyzed using the zeta potential, polydispersity index, surface-plasmon-resonance peak and transmission electron microscopy. A bioinformatics algorithm was used to predict the pairing of miRNA in the 3′untranslated-region (3′UTR) of MMP-9 mRNA. TaqMan assays were carried out to quantify miRNA and mRNA, whereas MMP-9-specific immunoassays and gelatin zymography were used to determine protein secretion and activity. The binding of miRNA in MMP-9 mRNA 3′UTR was verified by luciferase reporter clone assays and transfection with anti-miRNAs. In addition, NF-κBp65 activity was determined and confirmed with parthenolide treatment. Results: Engineered AuNPs were highly stable and spherical in shape, with a mean size of 28.3 nm. Tested in MCF-7 BC cells, microRNA-204-5p directly regulates MMP-9. AuNPs inhibit PMA-induced MMP-9 mRNA and protein via hsa-miR-204-5p upregulation. Anti-miR-204 transfected MCF-7 cells demonstrated enhanced MMP-9 expression (p < 0.001), while AuNPs treatment attenuated MMP-9 expression in a dose-dependent manner (p < 0.05). Moreover, AuNPs also inhibit PMA-induced NF-κBp65 activation in anti-hsa-miR-204 transfected MCF-7 cells. Conclusion: Engineered AuNPs were stable and non-toxic to BC cells. AuNPs inhibit PMA-induced MMP-9 expression, production and activation via NF-κBp65 deactivation and hsa-miR-204-5p upregulation. These novel therapeutic potentials of AuNPs on stimulated BC cells provide novel suggestions that AuNPs inhibit carcinogenic activity via inverse regulation of microRNAs.
Nazia Nazam, Nasimudeen R. Jabir, Iftikhar Ahmad, Saif A. Alharthy, Mohd Shahnawaz Khan, Rashid Ayub, and Shams Tabrez
MDPI AG
Cancer is a global health concern with a dynamic rise in occurrence and one of the leading causes of mortality worldwide. Among different types of cancer, ovarian cancer (OC) is the seventh most diagnosed malignant tumor, while among the gynecological malignancies, it ranks third after cervical and uterine cancer and sadly bears the highest mortality and worst prognosis. First-line treatments have included a variety of cytotoxic and synthetic chemotherapeutic medicines, but they have not been particularly effective in extending OC patients’ lives and are associated with side effects, recurrence risk, and drug resistance. Hence, a shift from synthetic to phytochemical-based agents is gaining popularity, and researchers are looking into alternative, cost-effective, and safer chemotherapeutic strategies. Lately, studies on the effectiveness of phenolic acids in ovarian cancer have sparked the scientific community’s interest because of their high bioavailability, safety profile, lesser side effects, and cost-effectiveness. Yet this is a road less explored and critically analyzed and lacks the credibility of the novel findings. Phenolic acids are a significant class of phytochemicals usually considered in the nonflavonoid category. The current review focused on the anticancer potential of phenolic acids with a special emphasis on chemoprevention and treatment of OC. We tried to summarize results from experimental, epidemiological, and clinical studies unraveling the benefits of various phenolic acids (hydroxybenzoic acid and hydroxycinnamic acid) in chemoprevention and as anticancer agents of clinical significance.
Bin Xue, Shah Mohammad Abbas Waseem, Zhixin Zhu, Mohammed A. Alshahrani, Nazia Nazam, Farah Anjum, Alaa Hamed Habib, Misbahuddin M. Rafeeq, Fauzia Nazam, and Monika Sharma
Frontiers Media SA
Brain-derived neurotrophic factor (BDNF) involving tropomyosin kinase B and low affinity p75 neurotropin receptors is the most abundant and researched neurotropins in mammal’s brain. It is one of the potential targets for therapeutics in Alzheimer’s disease (AD) owing to its key role in synaptic plasticity. Low levels of BDNF are implicated in the pathophysiology of neurological diseases including AD. However, a healthy lifestyle, exercise, and dietary modifications are shown to positively influence insulin regulation in the brain, reduce inflammation, and up-regulate the levels of BDNF, and are thus expected to have roles in AD. In this review, the relationship between BDNF, mental health, and AD is discussed. Insights into the interrelationships between nutrition, lifestyle, and environment with BDNF and possible roles in AD are also provided in the review. The review sheds light on the possible new therapeutic targets in neurodegenerative diseases.
Nazia Nazam, Aisha Farhana, and Sibhghatulla Shaikh
Springer Nature Singapore
Fauzia Nazam, Sibhghatulla Shaikh, Nazia Nazam, Abdulaziz Saad Alshahrani, Gulam Mustafa Hasan, and Md.Imtaiyaz Hassan
Springer Science and Business Media LLC
Rachel Topno, Nazia Nazam, Pallawi Kumari, Manoj Kumar, and Pallavi Agarwal
IOS Press
BACKGROUND: The breast cancer subtype deficient in estrogen receptor and human epidermal growth factor receptor-2 (ER-/HER2-) displays enhanced aggressiveness, metastasis and disease relapse due to chemoresistance. ER-/HER2- patients lack molecularly targeted treatment hence, new therapeutic and prognostic biomarkers are required for better patient management. OBJECTIVES: To investigate the prognostic role of protein tyrosine phosphatase genes in Breast Cancer and their relevance as predictive markers for chemoresistance. METHODS: We examined the expression of 114 protein tyrosine phosphatase (PTP) genes in 1700 breast cancer patient’s tumor samples with respect to ER-/HER2- subtype. Correlation of relevant candidates with chemoresistance was analyzed in breast cancer cells resistant to taxane/anthracycline based drugs. The prognostic value of key candidates was assessed using Kaplan Meier plots and Nottingham prognostic index and expression pattern was confirmed using qRT-PCR. The epigenetic regulation was analyzed using ChIP-Seq datasets. By plotting ROC plots, clinical outcome after treatment with taxane and anthracycline was established. RESULTS: Overexpression of CDC25A and CDC25C and under-expression of DUSP16 was observed in tumor samples of ER-/HER2- patients and breast cancer cells. Similar expression patterns of these candidate genes were observed in MCF7 cells resistant to paclitaxel and adriamycin and also correlated with poor prognosis of breast cancer patients. Increased CDC25A and CDC25C in ER-/HER2- cells was found to be regulated epigenetically by histone H3K4 methylation. Overall, the present study establishes increased expression of protein tyrosine phosphatase CDC25C as a poor prognostic marker for breast cancer. CONCLUSION: Our study highlights the role of CDC25C in chemoresistance to taxane and anthracycline based therapy and proposes CDC25C as a potential predictive marker for these cancer therapies.
Nazia Nazam, Mohammad Iqbal Lone, Abid Hamid, Talal Qadah, Alaa Banjar, Qamre Alam, Mohd Saeed, and Waseem Ahmad
MDPI AG
Dimethoate (DM) is an organophosphorus (OP) pesticide with wide use in the pest control. Its persistence in crops and soils could possibly cause adverse health consequences in humans as well as other non-target species. Since molecular studies confirming potential genotoxicity of DM have not been previously reported, the acute in vivo toxicological impact was evaluated in Wistar rats. Significant micronuclei induction and metaphase chromosome abnormalities in bone marrow cells exposed to three different DM doses (20, 40 and 60 mg/kg-bw) at multiple treatment durations (24, 48 and 72 h) indicated positive dose response relationship, confirming its genotoxic and cytotoxic potential. Significant mitotic index decrease was seen in dosed animals compared to vehicle control. The study used peripheral blood comet assay, indicating DM-mediated damage to DNA at all exposure levels in a time responsive manner. These assays were found to be an effective, precise, and fast technique with applied value in biomonitoring studies. Cell cycle and apoptosis along with mitochondrial membrane potential (MMP) in flow cytometric analyses confirmed DM exposure decreased MMP, affected the cell cycle, and inflicted DNA damage, which led to cellular apoptosis of leukocytes culminating into immunotoxic effects. The in silico experiments consequently augmented that DM showed acceptable binding energy value for Cyclin A2, suggesting that it could inhibit the cell cycle progression by inhibiting cyclin A2.
Sibhghatulla Shaikh, Nazia Nazam, Syed Mohd Danish Rizvi, Talib Hussain, Aisha Farhana, and Inho Choi
Bentham Science Publishers Ltd.
: Alzheimer’s disease (AD) is characterized by deposition of amyloid-β protein aggregates and an appropriate treatment strategy is urgently needed, as the number of diagnosed cases continues to increase. The management of AD and other brain-associated diseases is limited by the blood brain barrier and its selective control of drug passage. In fact, most of the promising drugs have restricted curative effects on AD owing to their lower bioavailability. Gold nanoparticles (AuNPs) have emerged as attractive therapeutic agents and have distinctive properties that could contribute to the development of a novel treatment strategy for neurodegenerative disorders. In this review article, we attempt to identify promising ways of developing competent AD therapeutic agents from anti-amyloid aggregating AuNPs. Initially, we discuss the current status of anti-amyloid inhibitors, the abilities of AuNPs to inhibit amyloid aggregation, and mechanistic aspects, and then describe plausible modifications that could aid the translation of AuNP-based therapeutics into neuromedicines. The review highlights some interesting characteristics that might effectively bridge the gap between laboratory and bedside treatments.
Sibhghatulla Shaikh, Nazia Nazam, Syed Mohd Danish Rizvi, Khurshid Ahmad, Mohammad Hassan Baig, Eun Ju Lee, and Inho Choi
MDPI AG
Multiple drug-resistant bacteria are a severe and growing public health concern. Because relatively few antibiotics have been approved over recent years and because of the inability of existing antibiotics to combat bacterial infections fully, demand for unconventional biocides is intense. Metallic nanoparticles (NPs) offer a novel potential means of fighting bacteria. Although metallic NPs exert their effects through membrane protein damage, superoxide radicals and the generation of ions that interfere with the cell granules leading to the formation of condensed particles, their antimicrobial potential, and mechanisms of action are still debated. This article discusses the action of metallic NPs as antibacterial agents, their mechanism of action, and their effect on bacterial drug resistance. Based on encouraging data about the antibacterial effects of NP/antibiotic combinations, we propose that this concept be thoroughly researched to identify means of combating drug-resistant bacteria.
Mohammad Iqbal Lone, Arisa Nabi, Nawab John Dar, Aashiq Hussain, Nazia Nazam, Abid Hamid, and Waseem Ahmad
Elsevier BV
Mohammad Iqbal Lone, Nazia Nazam, Aashiq Hussain, Shashank K Singh, Abid Hamid Dar, Rauf Ahmad Najar, Mohammed Hussein Al-Qahtani, and Waseem Ahmad
Informa UK Limited
ABSTRACT Dichloroethane is widely used as a solvent, degreasing agent and in a variety of commercial products, and is known for being a ubiquitous contaminant in the environment. Important sources principally include the emissions from industrial processes, improper consumption, storage, and disposal methods. In view of the fact that the mechanism of its genotoxicity has not been satisfactorily elucidated, the acute in vivo toxicological impact is assessed in Rattus norvegicus. A systematic investigation has been made involving the use of conventional methods along with molecular and flow cytometric approaches. The micronucleus and chromosomal aberration frequencies were significantly elevated in bone marrow cells exposed to three concentrations at multiple treatment durations indicating positive time- and dose-response relationships. The mitotic index significantly decreased in similar concentrations in contrast to normal control. Separate studies were performed on blood cells for comet assay. It revealed dichloroethane-induced DNA damage in all exposures readily explainable in a dose- and time-dependent manner. Recent molecular techniques were further employed using leukocytes for the cell apoptosis/cycle and mitochondrial membrane potential employing propidium iodide staining and rhodamine-123, respectively. The effect on mitochondrial membrane permeability, cell cycle phases, and the DNA damage was analyzed through flow cytometry. These indicators revealed dichloroethane treatment decreased the mitochondrial membrane potential, affected the cell cycle, and confirmed the DNA damage, leading to apoptosis of the cells of the immune system responsible for immunotoxic effects of dichloroethane on rat leukocytes.
Nazia Nazam, Sibhghatulla Shaikh, Mohammad Iqbal Lone, Monika Sharma, and Waseem Ahmad
Wiley
AbstractCombined in vivo and in silico studies were undertaken to gain insights into the change in mammalian brain acetylcholinesterase (AChE) activity under acute toxicity conditions in response to two representatives of organophosphates (OPs)—dichlorvos (DCV) and dimethoate (DM). In vivo experiments elucidated that DCV, at multiple sublethal doses for acute time periods, markedly reduced (10–25%) AChE activity, whereas with DM intoxication, a decrease in enzyme activity appeared to be lower, that is, (2–15%), in contrast to respective normal control (100%). Furthermore, a significant inhibition (P < 0.01) in the brain esterase activity was recorded for positive control animals treated with an alkylating agent—cyclophosphamide, with spontaneous reactivation at later time periods. In vivo results were further substantiated with in silico molecular docking analysis using “Autodock 4.2.” The lowest binding energy obtained through the computational study strongly augment that DCV binds to brain AChE with greater affinity compared with DM with reference to ∆G and Ki values. Thus, the animal biochemical assay and computational assessment suggest that DM is better to be used over DCV. The precautionary antidote for exposed humans can be developed prior to dealing with OPs. The study will aid in efficacious and safe clinical use of the above‐mentioned compounds.
Mohammad Iqbal Lone, Nazia Nazam, Sibhghatulla Shaikh, and Waseem Ahmad
Firenze University Press
The aim of this study was to evaluate possible genotoxic damage of dichlorophene stress in rats by chromosomal aberration (CA), micronucleus (MN) and mitotic index (MI) assays in bone marrow cells. The study was carried out in vivo using three sublethal concentrations, 66.9 mg, 133.8 mg and 200.7 mg kg–1 body weight of rat of dichlorophene administered intraperitoneally. The bone marrow cells were evaluated in each of the three treated groups at multiple durations. The MN and CA frequencies were increased significantly. A positive time- and dose-response relationship in all exposures was observed. However, the MI significantly decreased at each concentration compared to normal control. The results confirm the cytotoxic and genotoxic damage in Rattus norvegicus, and the suitability of the parameters for the screening of the genotoxicant is further discussed.
Nazia Nazam, Mohammad Iqbal Lone, Sibhghatulla Shaikh, and Waseem Ahmad
Walter de Gruyter GmbH
Abstract The possible genotoxic activity of Dichlorvos (2,2-Dichlorovinyl-O,O-dimethyl phosphate/DDVP, CAS No. 62-73-7), an organophosphorus insecticide was investigated employing three cytogenetic end points, i.e. micronucleus (MN) assay, mitotic indices (MI) and chromosome abberation (CA) analysis in vivo. The assays were carried out in hematopoietic bone marrow cells of Mus musculus at concentrations of 10, 20 and 30% of LD50 for intraperitoneal (ip) administration, corresponding to 0.06, 0.08 and 0.13 mg/kg Bwt, respectively. The normal control group received single ip dose of distilled water (2 ml/100 g Bwt), while animals of the positive group were injected with cyclophosphamide, a model mutagen (40 mg/kg Bwt) under identical conditions. The animals were sacrificed 24, 48 and 72 hrs post treatment. Under the present experimental conditions, there was no evidence of significant increase of MN frequencies at any dose or sampling time in polychromatic (PCE) and normochromatic (NCE) erythrocytes. The PCE/NCE ratio was not notably affected; however, a slight depression in prolonged exposure (48, 72 hr) intervals and a slight increase at the 24 hr interval were observed. Cells with various structural chromosome aberrations were noted but no significant (p<0.05; Man-Whitney U-test) differences in the frequencies of CA or mitotic indices (p<0.05; X2 test) were observed between Dichlorvos treated groups and the normal control group at doses or time intervals used. The results of the present investigation reflects a negative in vivo genotoxic potential of Dichlorvos at sublethal doses in bone marrow cells. Further studies are underway to confirm the presence or absence of genotoxic activity since compounds negative in genotoxic evaluation are susceptible of being carcinogens triggering cancer by genotoxic or non-genotoxic mechanisms.
Mohammad Niamat Ali, Nazia Nazam, Mohammad Iqbal Lone, Sibhghatulla Shaikh, and Waseem Ahmad
Elsevier BV
Riaz Ahmad, Nazia Nazam, Arshad Khan, and Mumtaz Alam
Centre for Evaluation in Education and Science (CEON/CEES)
Significance of Serum Lactate Dehydrogenase and its Isoenzymes During Post-Burn Follow-UpThe present study aims to evaluate the role of lactate dehydrogenase (LDH) isoenzymes in thermal burns. A total of 18 patients of both genders with 20 to 50% total burn surface area (TBSA), admitted to the Burn Ward of JN Medical College and Hospital was assessed. These patients were subjected to general and systemic examinations. The sera collected at day 1, 2, 5 and 10 during follow-up of burn patients were used for LDH quantitation. PAGE profiles showed significant differences in the levels of LDH isoenzymes in all the burn subjects (P=0.05). Software analysis of gel-scans showed the presence of five isoenzyme bands of which LDH-1 and -2 are the least contributors. During follow-up, it was observed that the ranking of LDH isoenzymes approaches control values at day 2 in 20% TBSA patients, while in the remaining cases it occurs at day 5. 3D-densitograms indicated high activity of LDH in 50% of TBSA patients even at day 10; however, the relative ranking of these isoenzymes was similar to control values (LDH-4>- 5>-3>-1>-2). We were of the opinion that the high activity of LDH enzyme is due to the enzyme-immunoglobulin-G (LDH-IgG) complex, but surprisingly we did not observe this complex in 50% of burn patients at any of the durations. Therefore, it is suggested that LDH isoenzymes play a role in the pathophysiology of the disease and can be an asset to ascertain the invisible tissue damage. Moreover, the high activity of LDH in 50% of burns is due to some unknown mechanism and not due to the binding of LDH with IgG.