Structure-bioactivity relationship study on anticancer Pd and Pt complexes with aliphatic glycine derivative ligands.

To investigate the structure and bioactivity relationship, six Pd(II)/Pt(II) complexes with N-isobutylglycine (L1) and cyclohexylglycine (L2) as N^O amino acid bidentate ligands, 1,10'-phenanthroline (phen) and 2,2'-bipyridine (bipy) as N^N donor ligands, and [Pd(L1)(bipy)]NO3 (1), [Pd(L2)(bipy)]NO3 (2), [Pd(L1)(phen)]NO3 (3), [Pd(L2)(phen)]NO3·2H2O (4), [Pt(L1)(phen)]NO3 (5), along with [Pt(L2)(phen)]NO3 (6) were prepared and then characterized. The geometry of each compound was validated by doing a DFT calculation. Furthermore, tests were conducted on the complexes' water solubilities and lipophilicity. All bipy complexes had superior aqueous solubility and less lipophilicity in comparison with phen complexes, as well as complexes containing cyclohexyl-glycine compared to isobutyl-glycine complexes, probably because of the steric effects and polarity of cyclohexylglycine. The in-vitro anticancer activities of these compounds were examined against HCT116, A549, and MCF7 cancerous cell lines. Data revealed that all Pd/Pt complexes demonstrate higher anticancer activity than carboplatin, and complexes 3 and 4 are more cytotoxic than cisplatin against the HCT116 cell line, particularly against MCF7 cancerous cells. In addition, among all compounds, complex 4 has more anticancer ability than oxaliplatin. Due to different solubility and lipophilicity behavior, the accumulation of Pt complexes and clinical Pt drugs in each cancerous cell was investigated. The binding capabilities of these complexes to DNA, as the main target in chemotherapy, occur through minor grooves and intercalate into DNA, which was done using absorption, fluorescence, and circular dichroism spectroscopy. Finally, the docking simulation study showed the mode of DNA bindings is in good agreement with the spectral binding data.

Smad4 Loss in the Mouse Intestinal Epithelium Alleviates the Pathological Fibrotic Response to Injury in the Colon.

Mucosal healing is associated with better clinical outcomes in patients with inflammatory bowel diseases (IBDs). Unresolved injury and inflammation, on the other hand, increases pathological fibrosis and the predisposition to cancer. Loss of Smad4, a tumor suppressor, is known to increase colitis-associated cancer in mouse models of chronic IBD. Since common biological processes are involved in both injury repair and tumor growth, we sought to investigate the effect of Smad4 loss on the response to epithelial injury. To this end, Smad4 was knocked out specifically in the intestinal epithelium and transcriptomic and morphological changes compared between wild type mice and Smad4 knock out mice after DSS-induced injury. We find that Smad4 loss alleviates pathological fibrosis and enhances mucosal repair. The transcriptomic changes specific to epithelium indicate molecular changes that affect epithelial extracellular matrix (ECM) and promote enhanced mucosal repair. These findings suggest that the biological processes that promote wound healing alleviate the pathological fibrotic response to DSS. Therefore, these mucosal repair processes could be exploited to develop therapies that promote normal wound healing and prevent fibrosis. NEW AND NOTEWORTHY: We show that transcriptomic changes due to Smad4 loss in the colonic epithelium alleviates the pathological fibrotic response to DSS in an IBD mouse model of acute inflammation. Most notably, we find that collagen deposition in the epithelial ECM, as opposed to that in the lamina propria, correlates with epithelial changes that enhance wound healing. This is the first report on a mouse model providing alleviated fibrotic response in a DSS-IBD mouse model in vivo .

Current knowledge on therapeutic, diagnostic, and prognostics applications of exosomes in multiple myeloma: Opportunities and challenges.

Interactions between the plasma cells and the BM microenvironment of Multiple myeloma (MM) take place through factors such as exosomes. Many studies have confirmed the role of exosomes in these interactions. By carrying proteins, cytokines, lipids, microRNAs, etc. as their cargo, exosomes can regulate the interactions between MM plasma cells and neighboring cells and participate in the signaling between cancer cells and the environment. It has been shown that MM-derived exosomes can induce angiogenesis, enhance osteoblast activity, confer drug resistance, and have immunosuppressive properties. Abnormal cargos in endosomes originating from MM patients, can be used as a cancer biomarker to detect or screen early prognosis in MM patients. The native nanostructure of exosomes, in addition to their biocompatibility, stability, and safety, make them excellent candidates for therapeutic, drug delivery, and immunomodulatory applications against MM. On the other hand, exosomes derived from dendritic cells (DC) may be used as vaccines against MM. Thanks to the development of new 'omics' approaches, we anticipate to hear more about exosomes in fight against MM. In the present review, we described the most current knowledge on the role of exosomes in MM pathogenesis and their potential role as novel biomarkers and therapeutic tools in MM.

Periodontitis: A Plausible Modifiable Risk Factor for Neurodegenerative Diseases? A Comprehensive Review.

The aim of this comprehensive review is to summarize recent literature on associations between periodontitis and neurodegenerative diseases, explore the bidirectionality and provide insights into the plausible pathogenesis. For this purpose, systematic reviews and meta-analyses from PubMed, Medline and EMBASE were considered. Out of 33 retrieved papers, 6 articles complying with the inclusion criteria were selected and discussed. Additional relevant papers for bidirectionality and pathogenesis were included. Results show an association between periodontitis and Alzheimer's disease, with odds ratios of 3 to 5. A bidirectional relationship is suspected. For Parkinson's disease (PD), current evidence for an association appears to be weak, although poor oral health and PD seem to be correlated. A huge knowledge gap was identified. The plausible mechanistic link for the association between periodontitis and neurodegenerative diseases is the interplay between periodontal inflammation and neuroinflammation. Three pathways are hypothesized in the literature, i.e., humoral, neuronal and cellular, with a clear role of periodontal pathogens, such as Porphyromonas gingivalis. Age, gender, race, smoking, alcohol intake, nutrition, physical activity, socioeconomic status, stress, medical comorbidities and genetics were identified as common risk factors for periodontitis and neurodegenerative diseases. Future research with main emphasis on the collaboration between neurologists and dentists is encouraged.

Distinctive Expression of Metastamirs in Breast Cancer Mesenchymal Stem Cells Isolated from Solid Tumor.

BACKGROUND: MSCs are a part of the tumor microenvironment, which secrete cytokines and chemokines. They can affect metastasis and the growth of tumors. metastamiRs are newly recognized regulatory elements of the metastasis pathway which are involved in epithelial-to-mesenchymal transition (EMT). OBJECTIVE: In the present study, we aimed to assess the expression profile of metastamiRs in the context of MSCs in correlation with their invasion and migration power. METHODS: tumor-isolated BC-MSCs and normal human mammary epithelial cells (HMECs) along with MCF-7, MDA-MB231, and MCF-10A cells were prepared and confirmed for their identity. The cells were assessed for CD44+CD24¯ percentage, Oct-4, and Survivin expression. GEO, KEGG, and TCGA databases were investigated to detect differential miR-expressions. Real-time PCR for 13 miRs was performed using LNA primers. Ultimately, Transwell-Matrigel assays as used to assess the level of migration and invasion. RESULTS: Our results indicated that some oncomiRs like miR-10b were upregulated in BC-MSCs, while the levels of miR-373 and miR-520c were similar to the MCF-10A. Generally, miR-200 family members were on lower levels compared to the other miR-suppressor (miR-146a, 146b, and 335). miR-31 and 193b were up-regulated in MCF-10A. The most invasiveness was observed in the MDA-MB231 cell line. CONCLUSION: We have demonstrated that the miR-expression levels of BC-MSCs are somewhat in between MCF-7 and MDA-MB231 miR-expression levels. This could be the logic behind the moderate level of invasion in BC-MSCs. Therefore, miR-therapy approaches such as miR-mimic or antagomiRs could be used for BC-MSCs in clinical cancer therapy.

Clodronic Acid has Strong Inhibitory Interactions with the Urease Enzyme of Helicobacter Pylori: Computer-aided Design and in vitro Confirmation.

BACKGROUND: Helicobacter Pylori (HP) infection could lead to various gastrointestinal diseases. Urease is the most important virulence factor of HP. It protects the bacterium against gastric acid. OBJECTIVE: Therefore, we aimed to design urease inhibitors as drugs against HP infection. METHODS: The DrugBank-approved library was assigned with 3D conformations and the structure of the urease was prepared. Using a re-docking strategy, the proper settings were determined for docking by PyRx and GOLD software. Virtual screening was performed to select the best inhibitory drugs based on binding affinity, FitnessScore, and binding orientation to critical amino acids of the active site. The best inhibitory drug was then evaluated by IC50 and the diameter of the zone of inhibition for bacterial growth. RESULTS: The structures of prepared drugs were screened against urease structure using the determined settings. Clodronic acid was determined to be the best-identified drug, due to higher PyRx binding energy, better GOLD FitnessScore, and interaction with critical amino acids of urease. In vitro results were also in line with the computational data. IC50 values of Clodronic acid and Acetohydroxamic Acid (AHA) were 29.78 ± 1.13 and 47.29 ± 2.06 µg/ml, respectively. Diameters of the zones of inhibition were 18 and 15 mm for Clodronic acid and AHA, respectively. CONCLUSION: Clodronic acid has better HP urease inhibition potential than AHA. Given its approved status, the development of a repurposed drug based on Clodronic acid would require less time and cost. Further, in vivo studies would unveil the efficacy of Clodronic acid as a urease inhibitor.

Safety and feasibility study of ex vivo expanded allogeneic-NK cells infusion in patients with acute pneumonia caused by COVID-19.

BACKGROUND: NK cells are the most active innate immune cells in antiviral immunity, which are impaired by SARS-COV2 infection. Infusion of allogeneic NK cells might be a complementary treatment to boost immune system function in COVID-19 patients. In this project, we focused on COVID-19 patients with low inspiratory capacity (LIC). This project aims to evaluate the feasibility and safety of allogeneic NK cell infusion as an intervention for respiratory viral disease. METHODS: A non-blind two arms pilot study was designed and conducted after signing the consent form. Ten matched patients, in terms of vital signs and clinical features, were enrolled in the control and intervention groups. Approximately 2 × 10^6 cells/kg of NK cells were prepared under GCP (good clinical practice) conditions for each patient in the intervention group. The control group was under the same conditions and drug regimen except for the treatment with the prepared cells. Then, infused intravenously during 20 min in the ICU ward of Masih Daneshvari Hospital. The clinical signs, serological parameters, and CTCAE (Common Terminology Criteria for Adverse Events) were recorded for safety evaluation and the feasibility of project management were evaluated via designed checklist based on CONSORT. RESULTS: There were no symptoms of anaphylaxis, hypersensitivity, significant changes in blood pressure, cardiovascular complications, and fever from injection time up to 48 h after cell infusion. The mean hospitalization period in the control and intervention groups was 10 and 8 days, respectively. The blood O2 saturation level was raised after cell infusion, and a significantly lower mean level of inflammatory enzymes was observed in the intervention group following discharge compared to the control group (p < 0.05). The inflammatory parameters differences at the discharge date in cell therapy group were highly negative. CONCLUSION: Intravenous infusion of ex vivo-expanded allogeneic NK cells was safe and feasible. However, the efficacy of this approach to reducing the severity of disease in COVID-19 patients with LIC could not be determined. TRIAL REGISTRATION: Name of the registry: NKCTC. IRCT20200621047859N2. December 29, 2020. URL of trial registry record: https://www.irct.ir/trial/49382.

Natural killer cell-derived exosomes for cancer immunotherapy: innovative therapeutics art.

Chimeric antigen receptor natural killer cells (CAR-NK) promote off-the-shelf cellular therapy for solid tumors and malignancy.However,, the development of CAR-NK is due to their immune surveillance uncertainty and cytotoxicity challenge was restricted. Natural killer cell-derived exosome (NK-Exo) combine crucial targeted cellular therapies of NK cell therapies with unique non-toxic Exo as a self-origin shuttle against cancer immunotherapy. This review study covers cytokines, adoptive (autologous and allogenic) NK immunotherapy, stimulatory and regulatory functions, and cell-free derivatives from NK cells. The future path of NK-Exo cytotoxicity and anti-tumor activity with considering non-caspase-independent/dependent apoptosis and Fas/FasL pathway in cancer immunotherapy. Finally, the significance and implication of NK-Exo therapeutics through combination therapy and the development of emerging approaches for the purification and delivery NK-Exo to severe immune and tumor cells and tissues were discussed in detail.

A multifunctional quinoxaline-based chemosensor for colorimetric detection of Fe3+ and highly selective fluorescence turn-off response of Cu+2 and their practical application.

A new dual responsive colorimetric and fluorescent turn-off sensor for Fe3+ and Cu2+ was designed and synthesized based on quinoxaline derivative by a simple procedure reaction. 2,3-bis(6-bromopyridin-2-yl)-6-methoxyquinoxaline (BMQ) was fabricated and characterized using ATR-IR, 13C and 1H NMR, and Mass spectroscopy. The interaction of BMQ with Fe3+ caused a significant color change from colorless to yellow. The sensing complex BMQ-Fe3+ with high selectivity was described to be 1:1 by the molar ratio plot. In this experiment, iron was detected by naked-eye using a recently synthesized ligand (BMQ). This color change was unexpectedly observed in iron-overloaded plasma, which had previously been admitted by AAS (Atomic Absorption Spectroscopy). Normal plasma, however, did not exhibit this color change. Interestingly, Cu2+ ions cause a quench at the local emission around 565 nm. On the other hand, receptor-binding selectivity for Cu2+ over a wide linear concentration range was observed through changes in the emission spectra. BMQ-Cu2+ was characterized to be 1:1 by the Job's plot. The emission intensity of BMQ-Cu2+ complex was balanced within only 1 min. various mineral water samples were analyzed for detecting Cu2+. The results show the great potential of the developed probe BMQ for the sensing of Cu2+ ions in mineral and drinking water samples.

Immunomagnetic Isolation of HER2-Positive Breast Cancer Cells Using a Microfluidic Device.

Analysis of circulating tumor cells (CTCs) as a tool for monitoring metastatic cancers, early diagnosis, and evaluation of disease prognosis paves the way toward personalized cancer treatment. Developing an effective, feasible, and low-cost method to facilitate CTC isolation is, therefore, vital. In the present study, we integrated magnetic nanoparticles (MNPs) with microfluidics and used them for the isolation of HER2-positive breast cancer cells. Iron oxide MNPs were synthesized and functionalized with the anti-HER2 antibody. The chemical conjugation was verified by Fourier transform infrared spectroscopy, energy-dispersive X-ray spectroscopy, and dynamic light scattering/zeta potential analysis. The specificity of the functionalized NPs for the separation of HER2-positive from HER2-negative cells was demonstrated in an off-chip test setting. The off-chip isolation efficiency was 59.38%. The efficiency of SK-BR-3 cell isolation using a microfluidic chip with a S-shaped microchannel was considerably enhanced to 96% (a flow rate of 0.5 mL/h) without chip clogging. Besides, the analysis time for the on-chip cell separation was 50% faster. The clear advantages of the present microfluidic system offer a competitive solution in clinical applications.

Novel delivery of sorafenib by natural killer cell-derived exosomes-enhanced apoptosis in triple-negative breast cancer.

Aim: We investigated the delivery of sorafenib (SFB) to breast cancer spheroids by natural killer cell-derived exosomes (NK-Exos). Methods: SFB-NK-Exos were constructed by electroporation. Their antitumor effects were evaluated by methyl thiazolyl tetrazolium, acridine orange/ethidium bromide, 4',6-diamidino-2-phenylindole, annexin/propidium iodide, scratch and migration assay, colony formation, RT-PCR, western blot and lipophagy tests. Result: The loading efficacy was 46.66%. SFB-NK-Exos-treated spheroids showed higher cytotoxic effects (33%) and apoptotic population (44.9%). Despite the reduction of SFB concentration in the SFB-NK-Exos formulation, similar cytotoxic effects to those of free SFB were observed. Increased intracellular trafficking, sustained release of the drug and selective inhibitory effects demonstrated efficient navigation. Conclusion: This is the first report for SFB loading into NK-Exos, which led to significant cytotoxic intensification against cancer cells.

What is this summary about? This study describes the delivery of an anticancer drug called sorafenib (SFB) to laboratory-grown spherical masses of cancer cells called spheroids. Saucer-like cellular structures called exosomes were used as drug-delivery tools. These exosomes were produced by a subgroup of immune cells called natural killer (NK) cells. NK cells are responsible for killing cancer cells. So, these exosomes share similar anticancer properties with NK cells. We wanted to test whether exosomes loaded with SFB would have better anticancer effects. What were the results? Using different methods, SFB was loaded within the exosomes and delivered to the spheroids. The obtained results showed that a combination of exosomes and SFB could improve the targeting efficacy, reducing the side effects to the normal cells and allowing continuous release of the drug. The spheroids were killed with higher efficacy following this treatment. What do the results of the study mean? The combination of NK cell-derived exosomes and SFB could lead to better cytotoxicity against cancer cells. Therefore, this strategy could have better anticancer effects compared with SFB treatment alone.

Psychometric assessment of the Persian version of the protective factors of resilience scale (PFRS).

BACKGROUND: Resilience is defined as an individual's ability to recover from difficulties and overcome challenges and adversity. Recognizing and measuring internal and external protective factors have been identified as important processes for building resilience, yet to date, no valid, and reliable scales of resilience in the Persian language have been developed that recognize both internal and external protective factors. METHODS: The present study was to translate the protective factors of resilience scale (PFRS) from English to Persian and analyze its psychometric properties among Iranians. Convenience sampling was used to gather data from January 2021 to February 2021 through digital internet scales, and 6 scales, including PFRS, Ryff's psychological well-being scale, Rosenberg self-esteem scale, life orientation test-revised, positive and negative affect schedule, and short version of resilience scale (RS), were completed by 265 participants aged from 15 to 56. So, the aim of this study is to investigate the psychometric properties of protective factors of resilience scale among Iranians. RESULTS: The results of the face, content, and construct validity revealed that the Persian version of the PFRS measure had acceptable validity and reliability. The Cronbach alpha for the whole scale was 0.88, and the value of the content validity index was above 0.7. A confirmatory factor analysis confirmed the three-factor structure model of the scale (fit indices: CMIN/df = 2.51, p < .01; comparative fit index = 0.94, goodness of fit index = 0.90, root mean squared error of approximation = 0.07). CONCLUSION: In conclusion, the Persian version of the protective factors of resilience is a reliable and valid measurement to assess the protective factors and internal and external protective factors of resilience in Iranians.

Impact of SNPs, off-targets, and passive permeability on efficacy of BCL6 degrading drugs assigned by virtual screening and 3D-QSAR approach.

B-cell lymphoma 6 (BCL6) regulates various genes and is reported to be overexpressed in lymphomas and other malignancies. Thus, BCL6 inhibition or its tagging for degradation would be an amenable therapeutic approach. A library of 2500 approved drugs was employed to find BCL6 inhibitory molecules via virtual screening. Moreover, the 3D core structure of 170 BCL6 inhibitors was used to build a 3D QSAR model and predict the biological activity. The SNP database was analyzed to study the impact on the destabilization of BCL6/drug interactions. Structural similarity search and molecular docking analyses were used to assess the interaction between possible off-targets and BCL6 inhibitors. The tendency of drugs for passive membrane permeability was also analyzed. Lifitegrast (DB11611) had favorable binding properties and biological activity compared to the BI-3802. Missense SNPs were located at the essential interaction sites of the BCL6. Structural similarity search resulted in five BTB-domain containing off-target proteins. BI-3802 and Lifitegrast had similar chemical behavior and binding properties against off-target candidates. More interestingly, the binding affinity of BI-3802 (against off-targets) was higher than Lifitegrast. Energetically, Lifitegrast was less favorable for passive membrane permeability. The interaction between BCL6 and BI-3802 is more prone to SNP-derived variations. On the other hand, higher nonspecific binding of BI-3802 to off-target proteins could bring about higher undesirable properties. It should also be noted that energetically less desirable passive membrane translocation of Lifitegrast would demand drug delivery vehicles. However, further empirical evaluation of Lifitegrast would unveil its true potential.

Biological Activity of Two Anticancer Pt Complexes with a Cyclohexylglycine Ligand against a Colon Cancer Cell Line: Theoretical and Experimental Study.

Because of their extraordinary ability to disrupt the natural structure of nucleic acids, metal complexes could be used in cancer therapy. In this study, cyclohexylglycine (HL) as a ligand and two new Pt complexes, [Pt(NH3)2(L)]NO3 (1) and [Pt(bipy)(L)]NO3 (2), were synthesized and characterized by elemental analysis, LC-MS, UV-vis spectrometry, FT-IR, 1H NMR spectroscopy, 13C NMR spectroscopy, 195Pt NMR spectroscopy, HPLC analysis, and single-crystal X-ray diffraction. Complex 2 crystallized in the orthorhombic Pbca space group, and density functional theory (DFT) was used to describe its structural parameters were described in detail. These complexes can be classified as oral medications and drug-like molecules based on a comparison of their absorption, distribution, metabolism, and excretion assessment. Quantum chemical descriptors (QCDs) were determined using DFT calculations to predict the tendency of DNA to approach these complexes. During the determination of the function of the metallodrug in DNA binding, the fluorescence data indicated that static quenching took place for all ligands and complexes with higher DNA binding affinity. CD and isothermal absorption studies indicate the presence of electrostatic and groove binding for the amine derivative and that DNA binds with the bipy moiety via groove binding. Furthermore, the interaction modes were determined using molecular docking to investigate the binding of these compounds with the target DNA molecule. According to docking investigations, binding energies of -5.7, -11.56, and -10.00 kcal/mol for HL and complexes 1 and 2, respectively, indicate partially electrostatic and groove binding. The anticancer activities of the Pt(II) complexes were tested against the HCT116 human colon cancer cell line, with IC50 values of 35.51 and 51.33 µM for 1 and 2, respectively, after 72 h. These values show that the inhibitory effect of complex 1 was better than those of 2 and carboplatin (IC50 = 51.94 µM).

Bioactivity of Exosomes Derived from Trained Natural Killer Cells versus Non-Trained One: More Functional and Antitumor Activity.

Background: Natural killer (NK) cells are cytotoxic lymphocytes of the innate immune system, capable of killing viral-infected and cancerous cells. NK cell-mediated immunotherapy has remarkably changed the current paradigm of cancer treatment in recent years. It emerged as a safe and effective therapeutic approach for patients with advanced-stage leukemia. Several immune-escape mechanisms can be enacted by cancer cells to avoid NK-mediated killing. Exosomes released by NK cells that carry proteins and miRNAs can exert an antitumor effect. In the present study, we hypothesized that maybe exosomes derived from trained natural killer cells show more antitumor effect in comparison to non-trained one. Methods: PBMC was separated by the Ficoll method and cultured with IL-2 for 21 days to expand NK cells. The NK cells were co-cultured with K562 for 72 hours and exosome-derived co-cultured (as trained) and natural killer cell-derived exosomes (as non-trained) were extracted by Exo kit. The exosomes were confirmed by dynamic light scattering (DLS), transmission electron microscopy (TEM), flow cytometry, and western blotting. The K562 cells were separately treated by trained and non-trained exosomes and MTT assay, apoptosis, and real-time PCR were performed. Results: Based on flow cytometry, CD56 marker was 89.7% and 40.1% for NK cells and NK-derived exosomes, respectively. CD63 and CD9 were positive for exosomes by western blotting. The morphology of exosome was confirmed by TEM. Treated K562 cells by trained exosomes indicated the diminished cell viability and higher apoptosis. Furthermore, the trained exosomes showed up-regulation in both P53 and caspase3 genes as compared with non-trained sample. Discussion. Trained Exos showed a potent inhibitory effect on proliferation and induced apoptosis on K562 cell lines compared to the same dose of non-trained Exos. According to the results of qRT-PCR, trained Exos exerted an antitumor activity through up-regulation of caspase 3 and P53 in the apoptotic signaling pathway in tumor cells. Our findings indicate an effective action of trained Exos against cancer cells.

Property evaluation of two anticancer candidate platinum complexes with N-isobutyl glycine ligand against human colon cancer.

Small molecules have potential usage in cancer therapy due to their remarkable potency of disarranging the natural structure of nucleic acids. In this study, two complexes [Pt(NH3)2(IBgly)]NO3 (1) and [Pt(bipy)(IBgly)]NO3 (2) based on Pt(II), N-isobutylglycine (IBgly), 2,2'-bipyridine, and ammonia were prepared and characterized by spectroscopic methods. Pharmacokinetic ADME data, absorption, distribution, metabolism, excretion, and bioavailability radar showed two complexes can be introduced for Pt-based anti-cancer drugs. Mechanism of tumor inhibition and DNA interaction of these compounds was studied by UV-Vis, fluorescence, and CD spectroscopies. Also, thermodynamic parameters and the binding constants were calculated through absorption measurements. The fluorescence data showed that a static quenching mechanism occurred for both complexes with a binding constant and binding affinity towards DNA (Kb ≈ 3500 M-1 and kq ≈ 2.1 × 1011 M-1 s-1). The thermodynamic parameters indicated electrostatic approaching and groove binding were more feasible than intercalation mode between Pt(II) complexes and DNA. CD spectra indicated the increasing intensity of the positive band and the negative band decreasing. Density functional theory calculations confirmed the experimental data and determined the quantum chemical descriptors including total energy, hardness, chemical potential, electrophilicity, electronegativity, etc. According to this, the binding tendency of these compounds with DNA could be predicted. Further, molecular docking studies were also performed. Docking studies revealed that the desolvation, hydrogen, and electrostatic binding were effective for the interaction between complexes and DNA with binding energy (- 10.44 and - 9.57 kcal/mol) for complexes 1 and 2, respectively, which is mainly of partially electrostatic and groove binding type. The cytotoxic activity of Pt complexes was examined against human colon cancer cell line which indicated good activity with IC50 values of (41.66 and 47.30 µM) for both complexes after 72 h, respectively. Also, they demonstrated more inhibitory effects compared to carboplatin.

Molecular mechanisms and therapeutic effects of different vitamins and minerals in COVID-19 patients.

COVID-19 is a rapidly spreading disease, which has caught the world by surprise. Millions of people suffer from illness, and the mortality rates are dramatically high. Currently, there is no specific and immediate treatment for this disease. Remedies are limited to supportive regiments and few antiviral and anti-inflammatory drugs. The lack of a definite cure for COVID-19 is the reason behind its high mortality and global prevalence. COVID-19 can lead to a critical illness with severe respiratory distress and cytokine release. Increased oxidative stress and excessive production of inflammatory cytokines are vital components of severe COVID-19. Micronutrients, metalloids, and vitamins such as iron, manganese, selenium, Zinc, Copper, vitamin A, B family, and C are among the essential and trace elements that play a pivotal role in human nutrition and health. They participate in metabolic processes that lead to energy production. In addition, they support immune functions and act as antioxidants. Therefore, maintaining an optimal level of micronutrients intake, particularly those with antioxidant activities, is essential to fight against oxidative stress, modulate inflammation, and boost the immune system. Therefore, these factors could play a crucial role in COVID-19 prevention and treatment. In this review, we aimed to summarize antiviral properties of different vitamins and minerals. Moreover, we will investigate the correlation between them and their effects in COVID-19 patients.

Naked Eye Chemosensor and In Vivo Chelating Activity of Iron (III) By Bromopyridine Quinoxaline (BPQ).

A wide variety of medical, biomedical, and industrial applications has been reported for quinoxalines derivatives. In this work, a novel quinoxaline derivative was designed and synthesized. Naked-eye and quantitative detection of Fe3+ among several cations were evaluated using UV-Vis spectroscopy. New chemosensor, 2,3-bis(6-bromopyridine-2-yl)-6-chloroquinoxaline named BPQ, showed a selective interaction for iron ion over other tested cations by changing color. Iron overloaded mice were prepared as a thalassemia model and then the effects of iron-chelating activities of BPQ were experienced. The job's plot methods determined the stoichiometric ratio of ligand to Fe3+ (1:1). The iron content in serum was evaluated by atomic absorption spectroscopy (AAS). Results showed significant differences (two-fold decrease in total iron and Fe3+) between the iron overloaded and BPQ (dose of 20 mgkg-1). The BPQ was identified as a ligand, which can be applied as a new chelator for decreasing the excess iron of blood.

Trace elements in the muscle tissue of Hemiculter leucisculus and Abramis brama orientalis from the Anzali International wetland, south-west of Caspian Sea: An exposure risk assessment.

High levels of trace elements in aquatic environments can affect the quality of seafood. We analyzed the concentrations of As, Cd, Co, Hg, Mn, Ni and Pb, in the edible muscles of Hemiculter leucisculus and A. brama orientalis caught in four different areas of southwest of the Caspian Sea. We estimated the potential risks for human health deriving by the oral consumption of these two species, and the Target Hazard Quotient (THQ) according to the US-EPA approach. THQ by adults and children was always below 1 for all stations. The greater contribution was given by Co, followed by Cd, Hg, Pb, Ni, As and Mn. Total-THQ was 0.538 and 0.246 for children and adults, respectively. Trace elements detected by our study were not elevated, highlighting a positive picture of the studied area and a lower risk of developing chronic systemic effects deriving from the consumption of local fish products.