The Effects of Nickel Oxide Nanoparticles on Structural Changes, Heme Degradation, Aggregation of Hemoglobin and Expression of Apoptotic Genes in Lymphocyte Cells

Nickel oxide nanoparticles (NiO NPs) have received great interests in medical and biotechnological applications. However, their adverse impacts against biological systems have not been well-explored. Herein, the influence of NiO NPs on structural changes, heme degradation and aggregation of hemoglobin (Hb) was evaluated by UV-visible (Vis), circular dichroism (CD), fluorescence, transmission electron microscopy (TEM), and molecular modeling investigations. Also, the morphological changes and expression of Bax/Bcl-2 mRNA in human lymphocyte cell exposed to NiO NPs were assayed by DAPI staining and quantitative real-time PCR (qPCR), respectively. The UV-Vis study depicted that NiO NPs resulted in the displacement of aromatic residues and heme groups and production of the pro-aggregatory species. Intrinsic and Thioflavin T (ThT) fluorescence studies revealed that NiO NPs resulted in heme degradation and amorphous aggregation of Hb, respectively, which the latter result was also confirmed by TEM study. Moreover, far UVCD study depicted that NiO NPs lead to substantial secondary alteration changes of Hb. Furthermore, near UV-CD displayed that NiO NPs cause quaternary structural changes of Hb as well as heme displacement. Molecular modelling study also approved that NiO NPs resulted in structural changes of Hb and heme deformation. Moreover, morphological and genotoxicity assays revealed that the DNA fragmentation and expression ratio of Bax/Bcl-2 mRNA increased in lymphocyte cells treated with NiO NPs for 24 hr. In conclusion, this study indicates that NiO NPs may affect the biological media and their applications should be limite

In vitro anticancer activity of hydrogen sulfide and nitric oxide alongside nickel nanoparticle and novel mutations in their genes in CRC patients

This study was carried out to assess the impact of nickel nanoparticles (NiNPs) as well as scorpion venom on colorectal cancer (CRC) cells in the presence and/or absence of 5-fluorouracil (5-FU), hydrogen sulfide (H2S), and nitric oxide (NO) donors and to determine alterations in endothelial NO synthase (eNOS) and cystathionine γ-lyase (CSE) enzyme-producing genes in CRC patients. The IC50 of both H2S and NO donors, along with NiNPs, were determined. The CRC cells were treated for 24hrs, and the cytotoxic activities were assessed using the MTT test. Moreover, the apoptosis was determined after 24hrs and 48hrs using TUNEL assay. Furthermore, the mutations in the eNOS gene (intron 4, -786T>C and 894 G>T) and CSE gene (1364GT) were determined using direct sequencing. The IC50 values for sodium disulfide (Na2S) and sodium nitroprusside (SNP) at 24hrs treatment were found to be 5 mM and 10−6 M, respectively, while the IC50 value for 5-FU was reached after 5-days of treatment in CRC cell line. Both black and yellow scorpion venoms showed no inhibition of cell proliferation after 24hrs treatment. Furthermore, Na2S showed a significant decrease in cell proliferation and an increase in apoptosis. Moreover, a co-treatment of SNP and 5-FU resulted in inhibition of the cytotoxic effect of 5-FU, while a combination treatment of NiNPs with Na2S, SNP, and 5-FU caused highly significant cytotoxicity. Direct sequencing reveals new mutations, mainly intronic variation in eNOS gene that has not previously been described in the database. These findings indicate that H2S promotes the anticancer efficiency of 5-FU in the presence of NiNPs while NO has antiapoptotic activity in CRC cell lines

Antioxidant properties of gold nanozyme: A review

AuNPs with enzyme-like features have received strong attention in different areas, although limited data is available in literature on their biological/industrial functions. NPs especially Au counterparts have been shown to functionally mimic the activity of antioxidant enzyme. Indeed, due to low cytotoxicity and SPR characteristics of AuNPs, there are a great number of reports in which Au nanozymes yield promising responses in biomedical applications. In this review, we aim to overview the enzymatic activity of Au nanozymes along with their regulatory and controlling mechanisms. We have reviewed the effect of various factors such as dimension, morphology, functionalization and presence of hybrid materials on the catalytic activity of Au nanozymes as well as a detail survey on the oxidase, peroxidase, SOD, and CAT-like activities of Au nanozyme. Finally, the significance of Au nanozymes in mitigating oxidative stress followed by conclusion and challenges were reported. Based on this paper, we envision that Au nanozymes can be used as a promising material to prevent oxidative stress-stimulated disorders

The interaction of silica nanoparticles with catalase and human mesenchymal stem cells: biophysical, theoretical and cellular studies

Aim: Nanoparticles (NPs) have been receiving potential interests in protein delivery and cell therapy. As a matter of fact, NPs may be used as great candidates in promoting cell therapy by catalase (CAT) delivery into high oxidative stress tissues. However, for using NPs like SiO2 as carriers, the interaction of NPs with proteins and mesenchymal stem cells (MSCs) should be explored in advance. Methods: In the present study, the interaction of SiO2 NPs with CAT and human MSCs (hMSCs) was explored by various spectroscopic methods (fluorescence, circular dichroism (CD), UV-visible), molecular docking and dynamics studies, and cellular (MTT, cellular morphology, cellular uptake, lactate dehydrogenase, ROS, caspase-3, flow cytometry) assays. Results: Fluorescence study displayed that both dynamic and static quenching mechanisms and hydrophobic interactions are involved in the spontaneous interaction of SiO2 NPs with CAT. CD spectra indicated that native structure of CAT remains stable after interaction with SiO2 NPs. UV-visible study also revealed that the kinetic parameters of CAT such as Km, Vmax, Kcat, and enzyme efficiency were not changed after the addition of SiO2 NPs. Molecular docking and dynamics studies showed that Si and SiO2 clusters interact with hydrophobic residues of CAT and SiO2 cluster causes minor changes in the CAT structure at a total simulation time of 200 ps. Cellular assays depicted that SiO2 NPs induce significant cell mortality, change in cellular morphology, cellular internalization, ROS elevation, and apoptosis in hMSCs at higher concentration than 100 μg/mL (170 μM). Conclusion: The current results suggest that low concentrations of SiO2 NPs induce no substantial change or mortality against CAT and hMSCs, and potentially useful carriers in CAT delivery to hMSC

The vasodilatory mechanism of nitric oxide and hydrogen sulfide in the human mesenteric artery in patients with colorectal cancer

Recent studies have focused on the role of gasotransmitters in cancer progression and prevention. Therefore, the current study was designed to explore the vasodilator activity of NO and H2S in the human mesenteric arteries of patients with colorectal cancer (CRC) via the activation of K+ channels. A total of two sets of experiments were established for the current investigation. Blood samples from patients with CRC were obtained to detect serum levels of endocan and malondialdehyde (MDA). The role of K+ channels in mediating the vasodilation of the human mesenteric artery in response to sodium nitroprusside (SNP) and sodium disulfide (Na2S) was assessed. The level of serum endocan was indicated to be decreased in patients with CRC compared with healthy individuals, while the level of serum MDA remained unaltered between groups. The arterial rings pre‑contracted with norepinephrine were first relaxed by the cumulative addition of increasing concentrations of either SNP (30 nM‑30 µM) or (1‑6 mM). Maximal relaxation rates were then calculated at 15 min intervals for 60 min. Pre‑incubation of arterial rings for 20 min with individual K+ channel blockers was indicated to significantly reduce SNP‑ and Na2S‑induced relaxation at different time points. Pre‑treatment of L‑nitro‑arginine methyl ester did not alter vasodilation that was induced by Na2S. Furthermore, vasodilation of the CRC mesenteric artery was not altered by the synergistic application of SNP and Na2S, while pre‑incubation of arterial rings with D,L‑propargylglycine significantly enhanced vasodilation induced by SNP. These results indicated that endothelial dysfunction and oxidative stress do not serve roles in the pathogenesis of CRC. The dilatory mechanisms of NO and H2S in mesenteric arteries of patients with CRC were K+ channel‑ and time‑dependent, and the activity of cystathionine γ‑lyase enzyme inhibited the ability of exogenous NO in vasodilation processes

Gold nanozyme: Biosensing and therapeutic activities

The utilization of AuNPs in therapeutic applications has been accelerated by discovering their catalytic activity consistent with the activity of natural enzymes. However, to reduce unwanted activities, it is imperative to fully understand their catalytic mechanisms to increase efficiency and safety. Therefore, along with other reports, we aimed to classify the enzymatic activity of Au nanozymes based on recent advance in their applications in biosensing and therapeutic activities. The results of the reported experiments indicate that the Au nanozymes can be used in biosensing of a wide range of agents such as molecule (H2O2 and glucose), ions, nucleic acids, proteins, cells, and pathogens. Furthermore, they can be used as potential candidates in inhibition of neurodegenerative diseases, cancer therapy, and antibacterial activities. Biosensing and therapeutic activities are generally based on colorimetric assays and the controlling the ROS level in the targeted cells, respectively. Finally, a brief explanation of the current challenges of the Au nanozymes in biomedical approaches was discussed. Indeed, this review holds a great promise in understanding the Au nanozymes properties and their development in biotechnology, medicine, and related industries

Molecular Study of IL-7R Gene Polymorphism and their Associations with Male Multiple Sclerosis Patients in Erbil Province.

Multiple sclerosis (MS) is an autoimmune disease in which immune cells attacks the body cells mistakenly; it is characterized by chronic inflammation that leads to demyelination and conduction of nerve impulse is affected negatively. The cause of the disease is unknown, but it may be partially under the control of genetics, including interleukin 7 receptor alpha (IL7Rα). In this case-control study, 40 relapsing-remitting MS (RRMS) male patients, which fulfills McDonald criteria and 40 healthy controls, with matched sex, were compared depending on the rs6897932 polymorphism within the exon 6 of IL7Rα gene by Tetra-amplification refractory mutation system polymerase chain reaction (Tetra-ARMS-PCR) method. The frequency of T allele of IL7Rα rs6897932 was considerably higher in male MS patients than healthy control males (31.25 vs 17.5%). Genotype distributions of the single nucleotide polymorphism (SNP) rs6897932 deviated from Hardy-Weinberg equilibrium with a p-value of 0.80. Both homozygous (TT) and Heterozygous (CT) were non-significantly positively associated with MS male patients (OR = 6.75, 95%CI = 0.73-62.4, p = 0.059, OR = 1.68, 95%CI = 0.64-4.38, p = 0.28) respectively. The distribution of the rs6897932 polymorphism is not significantly different in our case/control study in the Erbil provinc

Bladder Adenocarcinoma: A Case Report

Background: Bladder adenocarcinoma (AC) is a rare histological variant and research on the best ways to treat it is scant. Clinical Case: We present the case of a 70-year-old woman who has had hematuria for the past month with no history of serious illness. She visited a urologist, who performed a cystoscopy on her as a result. A urinary bladder adenocarcinoma was discovered in a biopsy. Complete investigations revealed no metastasis. The patient was considered for a partial cystectomy, according to the results of the MRI. She underwent the surgery, which was followed by concurrent chemo-radiotherapy. She underwent multiple reevaluations, and her case was stable after about a year of follow-up. Conclusions: With the best surgical outcomes, the choice to perform a partial cystectomy was appropriate given the tumor\u27s location. However, a lengthy follow-up is required

Combined chemo-magnetic field-photothermal breast cancer therapy based on porous magnetite nanospheres

The efficacy of different modalities of treating breast cancer is inhibited by several limitations such as off-targeted drug distribution, rapid drug clearance, and drug resistance. To overcome these limitations, we developed Lf-Doxo-PMNSs for combined chemo-MF-PTT. The PMNSs were synthesized by hydrothermal method and their physicochemical properties were examined by FE-SEM, TEM, DLS, TGA, XRD investigations. The cytotoxicity of as-synthesized NPs against 4T1 cells was carried out by MTT and flow cytometry assays. Afterwards, the anti-cancer activities of as-synthesized Lf-Doxo-PMNSs on the tumor status, drug distribution and apoptosis mechanism were evaluated. The anti-cancer assays showed that Lf-Doxo-PMNSs significantly suppressed the cancer cell proliferation and tumor weight by prolonging drug availability and potential drug loading in tumor cells; whereas they showed a minimum cytotoxicity against non-cancerous cells. Likewise, combined chemo-MF-PTT using Lf-Doxo-PMNSs displayed the highest anti-cancer activity followed by combined chemo-PTT and combined chemo-MF therapy based on altering the apoptosis mechanism. Therefore, these results showed that combined chemo-MF-PTT based on Lf-Doxo-PMNSs can be used as a promising therapeutic platform with potential targeted drug delivery and high loading capacity features as well as reducing cancer drug resistance

Exosomal circular RNA: a signature for lung cancer progression

Membrane vesicles having a diameter of 30–150 nm are known as exosomes. Several cancer types secrete exosomes, which may contain proteins, circular RNAs (circRNAs), microRNAs, or DNA. CircRNAs are endogenous RNAs that do not code for proteins and can create continuous and covalently closed loops. In cancer pathogenesis, especially metastasis, exosomal circRNAs (exo-circRNAs) have a crucial role mainly due to the frequently aberrant expression levels within tumors. However, neither the activities nor the regulatory mechanisms of exo-circRNAs in advancing lung cancer (LC) are obvious. A better understanding of the regulation and network connections of exo-circRNAs will lead to better treatment for LCs. The main objective of the current review is to highlight the functions and mechanisms of exo-circRNAs in LC and assess the relationships between exo-circRNA dysregulation and LC progression. In addition, underline the possible therapeutic targets based on exo-circRNA modulating