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It has been about a century since the discovery of the first antibiotic, and during this period, several antibiotics were produced and marketed. The production of high-potency antibiotics against infections led to victories, but these victories were temporary. Overuse and misuse of antibiotics have continued to the point that humanity today is almost helpless in the fight against infection. Researchers have predicted that by the middle of the new century, there will be a dark period after the production of antibiotics that doctors will encounter antibiotic-resistant infections for which there is no cure. Accordingly, researchers are looking for new materials with antimicrobial properties that will strengthen their ammunition to fight antibiotic-resistant infections. One of the most important alternatives to antibiotics introduced in the last three decades is antimicrobial peptides (AMPs), which affect a wide range of microbes. Due to their different antimicrobial properties from antibiotics, AMPs can fight and kill MDR, XDR, and colistin-resistant bacteria through a variety of mechanisms. Therefore, in this study, we intend to use the latest studies to give a complete description of AMPs, the importance of colistin-resistant bacteria, and their resistance mechanisms, and represent impact of AMPs on colistin-resistant bacteria. KEY POINTS: • AMPs as limited options to kill colistin-resistant bacteria. • Challenge of antibiotics resistance, colistin resistance, and mechanisms. • What is AMPs in the war with colistin-resistant bacteria?

Efferocytosis is the process by which apoptotic cells are removed without inflammation to maintain tissue homeostasis, prevent unwanted inflammatory responses, and inhibit autoimmune responses. Coordination of efferocytosis occurs via many surfaces and chemotactic molecules and adaptors. Recently, soluble positive or negative mediators of efferocytosis, have been more noticeable as non-invasive valuable biomarkers in prognosis and targeted therapy. These soluble factors can be detected in different bodily fluids, such as serum, plasma, and urine as a non-invasive method. There are lots of studies that have tried to show the importance of receptors and ligands in disorders; while a few studies tried to indicate the importance of soluble forms of receptors/ligands and their clinical aspects as a systemic compound and shedding of targets related to efferocytosis. Some of these soluble forms also can be as sensitive as specific biomarkers for certain diseases compared with routine biomarkers, such as soluble circulatory Lectin-like oxidized low-density lipoprotein receptor-1 vs. troponin T in the acute coronary syndrome. Thus, this review tried to gain more understanding about efferocytosis-related unwanted soluble receptors/ligands, their roles, the clinical significance, and potential for diagnosis, and prognosis related to different diseases.

Regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) are common immunosuppressive cells in the tumor microenvironment. These cells, through various mechanisms, inhibit antitumor immune responses and impede effective therapies. Therefore, designing an efficient protocol for inducing immune surveillance in tumors is highly recommended. Recently, nanoliposomes have provided broad-spectrum and state-of-the-art vehicles to deliver antigens or immune system compartments in immunotherapies. It has been shown that different lipids in the structure of liposomes and various liposomal formulations can affect immune responses in the tumor microenvironment. This study was aimed to evaluate the effects of four different liposomal formulations on MDSCs and Tregs in C26 tumor-bearing mice. To this end, after preparing liposomes, they were injected into tumor-inoculated mice and analyzed MDSC and Treg population and functions in spleen and tumor tissues. Results showed that DOTAP-containing liposomes reduced MDSC population and activity in the spleen, but not tumor, compared with other groups significantly (P

Introduction: With increasing antimicrobial resistance to common antibiotics, the development of alternative therapeutic strategies is necessary. Also, an antibacterial peptide with numerous behavior and different properties such as net charge, hydrophobicity, length, etc. could act against pathogenic microorganisms. In recent years, novel peptides with activity against a wide range of bacteria have been introduced. Methods: In this study, seventeen pathogenic bacteria were chosen to study the antibacterial effect of K4 peptide using MIC and MBC assays. The therapeutic index (TI) of this peptide was experimentally calculated by the ratio of HC50 to MIC as a parameter to represent the specificity of AMP. In silico analysis was performed to predict the physicochemical properties, structures, and behavior of this peptide. In vitro cytotoxic effect of peptide was evaluated on the Hela cell line using MTT assay, and the amount of macrophage nitric oxide production was measured by the Griess method on the J774 cell line. Results: Peptide concentrations of 25-400 µg/ml were seen as the MIC value results for different bacteria. MBC assay showed such a result with a concentration of more than 25-400 µg/ml. The result of the hemolysis assay was 24 percent at a 1 mg/ml concentration. The amount of nitric oxide production of macrophage cell line J774 was 25.9873 µM at a 6.3 µg/ml peptide concentration. Conclusions: K4 peptide had a strong antibacterial effect on some bacteria such as B. melitensis. This peptide may have a role in immunity with nitric oxide production. Additionally, it enhances the bacterial killing mechanism of macrophages, making this peptide a potential agent against pathogens.

Exposure to aflatoxin B1 can be associated with reproductive toxicity, accompanied by decreased sperm concentration in animal models. The aim of this meta-analysis was to determine the correlation between aflatoxin B1 exposure and sperm concentrations of male rodents (both mice and rats). According to inclusion and exclusion criteria, 8 articles were selected to assess in the current meta-analysis. The random effects and pooled analysis indicated that sperm concentration was decreased in mice [MD sperm = -20.79×10

Discovering novel antimicrobials is highly crucial to combat drug-resistant bacteria. Antimicrobial peptides (AMPs) are one of the compounds that are being studied as suitable candidates for antibiotics. Therefore, the aim of the present study was to investigate the antibacterial and cytotoxic properties of the d-leucine modified CM11 peptide. To assess the antibacterial activity, minimal inhibitory concentration (MIC), minimal bactericidal concentration (MBC) and bactericidal killing assay were utilized against multidrug-resistant (MDR)clinical isolates and standard strains of methicillin-resistant Staphylococcus aureus (MRSA),Escherichia coli, Pseudomonas aeruginosa and Salmonella enterica serovartyphi. In addition, the scanning electron microscope (SEM) was used to evaluate the effect of the peptide on the bacterial cell structure and morphology. Also, MTT assay was used to determine the cytotoxicity potential of the d-leucine modified CM11 peptide on the Vero cell line. d-leucine modified CM11 exhibited good bactericidal properties and the MIC and MBC values were ranged from 4 to 32 and 8–64 µg ml−1, respectively. The effect of the d-leucine modified CM11 peptide on the morphology and bacterial structures was confirmed by the SEM. The IC50 value of the d-leucine modified CM11 peptide against Vero cells was 160 µl.ml−1.Also, there was no significant difference between the toxicity of the d-leucine modified CM11 peptide with the original CM11 peptide (p > 0.05).Antibacterial and non-toxicity of the d-leucine modified CM11 peptide, which is reported for the first time in this study, speculate the use of this peptide as safe antibacterial agent.

To improve the low photocatalytic efficiency, powerful UV light activation, and facile electron transport of ZnFe2O4–CuO the combination of different C3N4 and N/B/RGO nanosheets in ZnFe2O4–CuO–C3N4 and ZnFe2O4–CuO-N/B/RGO ternary nanoheterojunction fabricated that lead to decrease recombination of electron/hole pairs and high photocatalytic efficiency for degradation of MO organic pollutants. The ZnFe2O4, ZnFe2O4-N/B/RGO, CuO-N/B/RGO, ZnFe2O4–CuO, ZnFe2O4–CuO-N/RGO, ZnFe2O4–CuO-B/RGO, ZnFe2O4–CuO-RGO, ZnFe2O4–CuO-N/B/RGO and ZnFe2O4–CuO–C3N4 photocatalysts were fabricated by sol–gel technique using melamine, zinc nitrate, ferric nitrate and copper nitrate hexahydrate as precursors. The prepared ZnFe2O4–CuO–C3N4 photocatalysts have a narrower bandgap than that of ZnFe2O4–CuO-N/B/RGO ternary heterojunction, resulting in higher photocatalytic activity for Fenton-type photodecomposition of methyl orange (MO). The activity of the compounds as a photocatalyst can be attributed to an electron transfer process on the surface of the photocatalyst, where the ZnFe2O4–CuO–C3N4 is a powerful electron donor and electron acceptor for the oxidized MO under ultra-violet (UV) light irradiation. ZnFe2O4–CuO–C3N4 ternary heterojunction photocatalyst show a red shift (lowest bandgap) in absorption and excellent photocatalytic degradation of MO. The particle sizes of ZnFe2O4 and CuO nanoparticles (NPs) were in the ranges of ~ 650–750 and ~ 50–150 nm, respectively. The CuO and ZnFe2O4 samples were displayed spherical and cubic morphology in FESEM images, respectively. Among the as-prepared nanostructures ZnFe2O4–CuO–C3N4 show the highest photocatalytic activity and eliminate 95.84% (80 min) of methyl orange under UV light irradiation.

Drug-resistant infectious diseases have increased in recent years. Accordingly, plenty of researches are exploring novel approaches to overcome this problem. In this era, antimicrobial peptides have been identified as potential antibacterial agents. The Modified CM11 (mCM11) was designed with the C-terminal amidation and substitution of lysine with arginine. The designed peptide was synthesized by the solid-phase method and Rink amide p-methyl-benzhydryl amine resin. The synthesized peptide was evaluated using Mass Spectrometry (MS), High-Performance Liquid Chromatography (HPLC), and Circular Dichroism (CD). Finally, the antibacterial, cytotoxic, and apoptotic effect of the mCM11 peptide was investigated. The new peptide indicated a beta-sheet structure with a molecular weight of 1527.50 D and purity of 96%. The peptide exerted a potent antimicrobial activity against gram-negative and positive bacteria. The minimum inhibitory concentration (MIC) and minimum bacterial concentration (MBC) ranged from 16 to 64 µg/ml, and 16 to 128 µg/ml, respectively. The IC50 of mCM11 was 16 µg/ml and its cytotoxicity in SH-SY5Y cell line revealed a dose-dependent manner. Also, apoptosis analysis of eukaryotic cells revealed a decline in late apoptosis and necrosis in comparison with untreated cells. The mCM11 indicated a considerable antibacterial effect against a wide range of pathogenic bacterial strains. Further, it did not represent any late apoptotic and necrosis impact on the eukaryotic cell line. All of these findings may confirm the potential role of this new peptide as an effective therapeutic agent.

Purpose Brucellosis as a worldwide zoonotic illness affect domestic animals and humans doesn't have any vaccine for the prevention of infection in humans yet. The aim of this study was to evaluate the specific immune response following the administration of glycine nanoparticles as adjuvant and delivery system of a chimeric antigen contained trigger factor, Omp31, and Bp26 in murine model. Materials and methods The chimeric antigen of Brucella was cloned and expressed in Escherichia coli (E. coli) BL21 (DE3). Purification and characterization of recombinant protein was conducted through Ni-NTA (nickel-nitrilotriacetic acid) agarose, SDS-PAGE (sodium dodecyl sulfate-polyacrylamide gel electrophoresis), and Western blot. Nanoparticle characteristics including morphology, particle size distribution, zeta potential, protein retention rate, and release rate were measured in vitro. Subsequently, nanoparticle contained antigen was administered to mice and blood sample was taken to measured the antibody level. Results The protein retention in the nanoparticles was successfully done and the nanoparticle characteristics were appropriate. The average size of glycine particles containing antigen was about 174 nm, and the absorption of protein was approximately 61.27% of the initial value, with a release rate of approximately 70% after 8 hours. Enzyme-linked immunosorbent assay result proved that the immunized sera of mice which were administered with nano-formula contains high levels of antibodies (immunoglobulin G) against recombinant chimeric antigen and also a high level of mucosal antibody (immunoglobulin A) in the oral group, which showed a desirable immunity against Brucella. Conclusion The results showed that chimeric antigen-loaded glycine nanoparticles can act as a vaccine candidate for inducing the cellular and humoral immune response against brucellosis.

In the present study, a series of all-atom molecular dynamics simulations were applied to shed light on the molecular mechanism of the activity of CM11, a short cecropin–melittin hybrid peptide obtained through a sequence combination approach, against gram-positive (GP) and gram-negative (GN) bacterial membrane models. In addition, the peptide adsorption mechanism on the surface of the membrane models, the thermodynamic and structural contribution of each residue in the antibacterial activity of the peptide against both GP and GN bacterial membranes were investigated. Our findings showed that the peptide was strongly bound to the GP membrane type in comparison with the GN membrane and was stabilized quickly. These strong bonds are caused by the interactions between basic residues and POPG molecules, which have higher concentrations in GP than GN membranes. Calculation of binding free energies revealed that both electrostatic and van der Waals energy components were desired for the peptide binding and insertion in the membrane. Electrostatic interactions were the main driving force in the adsorption and surface localization of the peptide. Determining the contribution of each residue to the binding free energy indicated that W1, K2, K5, K6 and K9 residues played an important role in the activity of the peptide. These results can be used as a roadmap to provide in-depth insights into the design of appropriate peptides in the fight against multidrug-resistant bacteria.

To promote the low photocatalytic efficiency caused by the recombination of electron/hole pairs and widen the photo-response wavelength window, ZnFe2O4@ZnO-N/B/RGO and ZnFe2O4@ZnO-C3N4 ternary heterojunction nanophotocatalysts were designed and successfully prepared through a sol–gel technique. In comparison to bare ZnFe2O4 and ZnO, the ZnFe2O4-ZnO@N/B/RGO and ZnFe2O4@ZnO-C3N4 ternary products showed highly improved photocatalytic properties in the degradation of methyl orange (MO) under ultra-violet (UV) and visible light irradiation. Various physicochemical properties of the photocatalysts were evaluated through field emission scanning electron microscopy (FESEM), energy-dispersive X-ray (EDX) analysis, X-ray diffraction (XRD), UV–visible diffuse reflectance spectroscopy (DRS), Fourier transform infrared spectroscopy (FT-IR), and vibrating sample magnetometer (VSM) techniques. The observations indicated that the ternary heterojuncted ZnFe2O4@ZnO-N/B/RGO absorbs lower energy visible light wavelengths, which is an enhancement in the photocatalytic properties of ZnFe2O4@ZnO loaded on reduced graphene oxide (RGO) nanosheets and graphite-like carbon nitride (g-C3N4). This gives the catalyst photo-Fenton degradation properties.

Introduction Vaccine formulation with appropriate adjuvants is an attractive approach to develop protective immunity against pathogens. Calcium phosphate nanoparticles (CaPNs) are considered as ideal adjuvants and delivery systems because of their great potential for enhancing immune responses. In the current study, we have designed nanoparticle-based vaccine candidates to induce immune responses and protection against B. melitensis and B. abortus. Materials and methods For this purpose, we used three Brucella antigens (FliC, 7α-HSDH, BhuA) and two multi-epitopes (poly B and poly T) absorbed by CaPNs. The efficacy of each formulation was evaluated by measuring humoral, cellular and protective responses in immunized mice. Results The CaPNs showed an average size of about 90 nm with spherical shape and smooth surface. The CaPNs-adsorbed proteins displayed significant increase in cellular and humoral immune responses compared to the control groups. In addition, our results showed increased ratio of specific IgG2a (associated with Th1) to specific IgG1 (associated with Th2). Also, immunized mice with different vaccine candidate formulations were protected against B. melitensis 16M and B. abortus 544, and showed same levels of protection as commercial vaccines (B. melitensis Rev.1 and B. abortus RB51) except for BhuA-CaPNs. Discussion Our data support the hypothesis that these antigens absorbed with CaPNs could be effective vaccine candidates against B. melitensis and B. abortus.

Parkinson’s disease (PD) is a widespread neurological disorder mainly characterized by gradual death of dopaminergic neurons in the basal ganglia. In our study, we compared the effects of curcumin (Curc) as a herbal medicine and those of allopregnanolone (Allo) as a synthetic drug on arsenic(Ars-)-induced toxicity in an SH-SY5Y in vitro model of PD. Cell survival was determined by the MTT assay; intracellular reactive oxygen species (ROSs) and the mitochondrial potential were assessed by a fluorescence probe. Furthermore, immunoblotting was applied to determine the biomarkers of cells apoptosis. As was found, Ars decreases the cell survival rate and enhances the loss of the mitochondrial membrane potential. The mean contents of intracellular ROSs, amount of c-Fos, and caspase-3 ratio significantly increased in Ars-exposed cells. Pretreatment of cells with Allo (250 μM) and Curc (5 μM) significantly decreased mean levels of these factors in Ars-treated cells. Although Curc showed a greater protective effect than Allo, the respective difference was statistically insignificant. The neuroprotective effects of Allo and Curc are probably related to their antioxidant and anti-apoptotic properties, which suggests their therapeutic potential in PD treatment.

Toxoplasma gondii (T. gondii) causes considerable financial losses in the livestock industry and can present serious threats to pregnant women, as well as immunocompromised patients. Therefore, it is required to design and produce an efficient vaccine for controlling toxoplasmosis. The present study aimed to evaluate the protective immunity induced by RMS protein (ROP18, MIC4, and SAG1) with Freund adjuvant, calcium phosphate nanoparticles (CaPNs), and chitosan nanoparticles (CNs) in BALB/c mice. The RMS protein was expressed in Escherichia coli (E. coli) and purified using a HisTrap HP column. Thereafter, cellular and humoral immunity was assessed by injecting RMS protein on days 0, 21, and 35 into four groups [RMS, RMS-chitosan nanoparticles (RMS-CNs), RMS-calcium phosphate nanoparticles (RMS-CaPNs), and RMS-Freund]. Phosphate buffered saline (PBS), CNs, CaPNs, and Freund served as the four control groups. The results displayed that vaccination with RMS protein and adjuvants significantly elicited the levels of specific IgG antibodies and cytokines against toxoplasmosis. There were high levels of total IgG, IgG2a, and IFN-γ in vaccinated mice, compared to those in the control groups, especially in the RMS-Freund, indicating a Th-1 type response. The vaccinated and control mice were challenged intraperitoneally with 1 × 10

Many recent studies have been conducted to find new DNA vaccines based on Toxoplasma gondii antigens. DNA vaccines encoding complex of different antigens showed better immune responses compared to single antigen vaccine. In this study, we constructed a DNA vaccine encoding SAG1, SAG3, MIC4, GRA5, GRA7, AMA1 and BAG1 against T. gondii, and evaluated the immune response it induced in BALB/c mice. For this purposes, thirty BALB/c mice were randomly divided into three groups containing tenmice each. There were two negative control groups (PBSand pVAX1 vector) and one vaccination group (pVAX1-MAF, Multantigenic Fragment). On days 0, 14 and 28, the mice were immunized intramuscularly, and 5 weeks later they were challenged with T. gondii RH strain. The immune responses were evaluated using lymphocyte proliferation assay, T-cell subsets detection, and measurement of antibody and cytokine levels. The results showed that mice immunized with pVAX1-MAF developed high levels of IL-2, IL-12, IgG and IFN- γ as well as CD3

Gd3+-, Pr3+- or Sm3+-doped Co-Zn (Co0.5Zn0.5Fe2O4) magnetic ferrites (i.e., Co0.5Zn0.5Gd0.1Fe1.9O4, Co0.5Zn0.5Pr0.1Fe1.9O4 and Co0.5Zn0.5Sm0.1Fe1.9O4) were prepared using a facile sol-gel approach, and the structure, surface morphology and chemical composition of the products were studied by means of scanning electron microscopy (SEM), energy dispersive X-ray analysis (EDX), X-ray diffraction (XRD), UV-visible diffuse reflectance spectroscopy (DRS), photoluminescence (PL) spectroscopy, Fourier transform infrared spectroscopy (FT-IR) and vibrating sample magnetometer (VSM) spectroscopy. XRD patterns show the Co-Zn product is composed of cubic spinel phases with few impurities or secondary phases, and the average crystallite sizes of the samples are determined to be approximately ∼51–80, ∼99–181, ∼68–103 and ∼83–133 nm. Also the coercivity and remnant and saturation magnetizations, evaluated by vibrating sample magnetometer (VSM), are found to increase linearly with the incorporation of Gd3+, Pr3+ and Sm3+ in the product formulation. The Co1−xZnxFe2−yRyO4 photocatalyst sample is found to display a red shift in its absorption, and exhibits outstanding photocatalytic effects in the degradation of MO under ultraviolet (UV) light. This is attributed to the reduction of the band gap of cobalt-zinc ferrite due to the presence of rare earth ions. Further in vitro evaluations of the cytotoxic effects of the synthesized nanoparticles were performed on a HeLa cell line.

In the last century, the emergence of in silico tools has improved the quality of healthcare studies by providing high quality predictions. In the case of COVID-19, these tools have been advantageous for bioinformatics analysis of SARS-CoV-2 structures, studying potential drugs and introducing drug targets, investigating the efficacy of potential natural product components at suppressing COVID-19 infection, designing peptide-mimetic and optimizing their structure to provide a better clinical outcome, and repurposing of the previously known therapeutics. These methods have also helped medical biotechnologists to design various vaccines; such as multi-epitope vaccines using reverse vaccinology and immunoinformatics methods, among which some of them have showed promising results through in vitro, in vivo and clinical trial studies. Moreover, emergence of artificial intelligence and machine learning algorithms have helped to classify the previously known data and use them to provide precise predictions and make plan for future of the pandemic condition. At this contemporary review, by collecting related information from the collected literature on valuable data sources; such as PubMed, Scopus, and Web of Science, we tried to provide a brief outlook regarding the importance of in silico tools in managing different aspects of COVID-19 pandemic infection and how these methods have been helpful to biomedical researchers.

SARS-CoV-2 is a corona virus that has been the cause for one of the deadliest pandemics of history, started since 2019. Suppressing the activity of the critical enzymes in the SARS-CoV-2 could potentially inhibit a vital step in viral life cycle. Papain-like protease (PLpro) could be regarded as a critical enzyme in viral replication of SARS-CoV-2. In this research, it was aimed to suppress the activity of PLpro enzyme by using potential plant-derived protease inhibitor peptides. For this purpose, 11 plant derived peptides that could potentially inhibit protease activity were selected from literature. The structures of the PLpro and the peptide ligands were acquired from PDB (protein data bank) and after structural optimization, were docked by using HADDOCK 2.4 program. Analyzing the results indicated that VcTI from Veronica hederifolia provides effective molecular interactions at both liable Zn site and classic active site of PLpro, making it a potential inhibitory ligand for this enzyme that could be used for halting the replication of SARS-CoV-2. Molecular dynamic assay confirmed that the selected receptor and ligand complex was stable. Future in vitro and in vivo investigations are required to verify the efficiency of this compound as a potential therapeutic against SARS-CoV-2 infection. Supplementary Information The online version contains supplementary material available at 10.1007/s10989-021-10331-8.

Multi-drug resistance, which is the consequence of overusing antibiotics, has been shown to become a common problem in the medical environments. Accordingly, finding a substitute for daily used antibiotics is a topic of interest in medical microbiology and biotechnology. Antimicrobial peptides (AMPs) are among the main candidates for controlling this problem. These peptides are regarded as the critical defensive line in many organisms. These AMPs act as an innate immunity against pathogenic microorganisms; such as bacteria or fungi. AMPs could destroy their target via different methods; including membrane pore-formation or by targeting their intracellular targets and disrupting the normal cellular activity. Some AMPs have the property of targeting constructs like DNA, RNA, protein synthesis and folding and inhibiting cell life activities; such as normal metabolism or cell division. At this study, we reviewed more than 130 papers that were concerning the importance of intracellular targeting AMPs, by searching the valuable data sources such as PubMed, Scopus, and Web of Science. These AMPs can be considered as one of the possible options to improve the treatment of infected patients. In this review, it was aimed to discuss the activity of intracellular AMPs and provide an outlook for future studies.

In the present work, the anticancer, photocatalytic and magnetic qualities of nanocrystalline nickel or magnesium-doped nanoparticles of lithium-ferrite samples, formed through sol–gel auto-combustion process were investigated. The products were studied by FT-IR spectroscopy, scanning electron microscopy (SEM), energy dispersive X-ray (EDX) technique, X-ray diffraction (XRD), ultraviolet–visible diffuse reflectance spectroscopy (DRS), photoluminescence (PL) spectra, and vibrating sample magnetometery (VSM). XRD results showed that the nano-photocatalytic samples lithium ferrite (Li0.5Fe2.5O4), lithium-magnesium ferrite (LiMg0.5Fe2O4) and lithium-nickel ferrite (LiNi0.5Fe2O4) are nano-photocatalytic samples, which are in good crystalline form. The LiMg0.5Fe2O4 nano-photocatalyst showed the highest photocatalytic performance for removal of methyl orange (MO) and removed 99.9% of pollutant within 25 min under ultraviolet (UV) light irradiation. Magnetic characterization revealed that the Mr and Ms of LiNi0.5Fe2O4 nano-photocatalyst decreases with doping Ni or Mg. Finally, in vitro cytotoxic effect of synthesized nanoparticles was evaluated on Hela cell line.

Toxoplasma gondii is an obligate intracellular parasite that causes one of the most common parasitic infections in humans and other warm-blooded animals. Currently, there are no effective treatments for inhibiting the formation of chronic tissue cysts in infected hosts. Thus, the development of a vaccine to protect against toxoplasmosis is an attractive option for avoiding infection. The aim of this study was to design an epitope-based vaccine for T. gondii. In the present study, an in silico approach was used to predict and analyze B-cell and T-cell epitopes and the transmembrane domain of proteins SAG1, MIC3, and ROP8. We also predicted the antigenicity, allergenicity, secondary and tertiary structures, and physicochemical characteristics of a chimeric protein. Next, codon optimization and mRNA structure prediction were conducted using bioinformatics tools, and the designed construct was chemically synthesized and cloned into the pET28a vector. SAG1 (amino acid positions 85–235), MIC3 (30–180), and ROP8 (85–185) were found to have several strong immunodominant epitopes that were joined with a rigid linker A(EAAAK)2A. Although the resultant protein called MRS ( M IC3, R OP8, and S AG1) did not turn out to be an allergen, its antigenicity was estimated to be 0.7983. Additionally, MRS was selected as the best vaccine candidate on the basis of its secondary and tertiary structures. The number of amino acids, molecular weight, and numbers of negatively and positively charged residues of MRS were 427 and 45,661.31 Da, 45, and 50, respectively. ΔG of the best-predicted structure was −413.0 kcal/mol, and the first nucleotides at the 5′ end did not form a stable hairpin or pseudoknot. Finally, successful expression and verification of the expressed MRS protein showed that in silico analysis was almost accurate. This vaccine candidate selected by in silico tools should be validated in experimental studies.

The mucosal immune system serves as the first line of defense against Bordetella pertussis. Intranasal vaccination, due to its potential to induce systemic and mucosal immune responses, appears to ...

Gastrointestinal Infectious diseases (GIDs) are the second cause of death worldwide. T helper17 cells (Th17) play an important role in GIDs through production of IL-17A, IL-17F, and IL-22 cytokines. Because of their increased activities in GID, Th17 and its inflammatory cytokines can inhibit the progression and eliminate the infection. Actually, although Th17 have the best performance in the acute phase, regulatory T cells (Treg cells) are enhanced in the chronic phase and infection progress through its suppressive function. In addition, Treg cells prevent undesirable inflammatory damages developed by immune system components. On the other hand, miRNAs have important roles in the regulation of immune responses to eliminate bacterial infections and protect host organisms from harmful effects. Actually, miRNAs can reinforce innate and adaptive immunity to remove infections. Of note, miRNAs can develop a regulatory network with the immune system. Additionally, miRNAs can also serve in favor of bacteria to reduce immune responses. Therefore, balance of immune responses in Treg and Th17 cells can influence outcome of many infectious diseases. In conclusion, there is an imbalance in the Treg/Th17 ratio in GIDs; importantly, sets of miRNAs, particularly miR155 and miR146, were determined to be involved clearly in GIDs.

Yb3+- and Pr3+-substituted cobalt–nickel ferrite nanoparticles were prepared through a sol–gel auto-combustion procedure and the effects on the cytotoxic, photocatalytic and magnetic characteristics of the resulting compounds were evaluated. As an initial step, the structure, morphology and magnetic properties of the produced particles were assessed using X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), energy dispersive X-ray (EDX), UV–visible diffuse reflectance spectroscopy (DRS), photoluminescence (PL), and vibrating sample magnetometery (VSM) techniques. The crystalline size and nanoparticles size of prepared nanostructures was in the range of 100–180 and 90–220 nm based on XRD and SEM results. Using the XRD results it was found that the product had a spinel cobalt–nickel ferrite phase structure, also containing some PrFeO3 and YbFeO3 phases as impurities. VSM results exhibited that Co0.5Ni0.5Pr0.1Fe1.9O4 has higher magnetic parameters than Co0.5Ni0.5Yb0.1Fe1.9O4, yet but the latter enjoys enhanced photocatalytic activity in degrading methyl orange (MO) under ultraviolet (UV) light irradiation.

To develop a possible PET blood pool imaging agent, a series 68Ga-dextran carboxylate derivatives were prepared. Dextran carboxylates with different degree of oxidations (DO) were prepared through stepwise dextran oxidation using NaIO4 and CH3COOOH. The products were characterized by FT-IR and GPC, followed by solubility and toxicity tests on Hella cells (viability=98.6, 97.4 and 95.6% for 3 dextran carboxylates with DOs: 8.3, 24.6 and 39.8%, respectively. The products were labeled with 68Ga (radiochemical purity>98%; ITLC) followed by stability tests in final solution as well as in presence of cycteine and human serum. Two stable tracers (DOs; 24.6 and 39.8%) were adminstered intravenously into wild type rat tail vein separately demonstrating suitable retention in circulation as expected from blood pool imaging agents. Liver and spleen also contained activities. The major excretion was through urinary pathway esp. for derivative with DO. 39.8%. Unlike 68Ga-dextran, lungs showed lower uptake. The dextran carboxylate with the highest 39.8% showed the best characteristics for a blood pool agent, though more studies including PET imaging in larger mammals are required.

Two pH-responsive polysaccharide-based magnetite nanocarriers have been developed from modified salep and PEGylated chitosan decorated onto the surface of magnetite nanoparticles for active loading and targeted delivery of doxorubicin. The first nanocarrier was formed via imine bond formation and electrostatic hydrogen bonding interactions between dialdehyde salep-modified magnetite nanoparticles and DOX in a one-layered nanocarrier fashion. Subsequently, PEGylated chitosan was used as a second layer on the surface of the first nanocarrier, mainly by the same interactions, producing a double-layered polysaccharide-based nanocarrier. In vitro release studies indicated that the use of PEGylated chitosan as the second shell provides more control on the rate and amount of DOX release and makes double-layered nanocarrier more pH-sensitive. Magnetic heating capacity of double-layered nanocarrier was investigated and release profile under AMF (42 °C, magnetically induced) showed a good improvement in the time an...

The inflammasome as a multiprotein complex has a role in activating ASC and caspase-1 resulting in activating IL-1β in various infections and diseases like corona virus infection in various tissues. It was shown that these tissues are affected by COVID-19 patients. According to the current evidence, melatonin is not veridical while possessing a high safety profile, however, it possesses indirect anti-viral actions owing to its anti-oxidation, anti-inflammation, and immune improving properties. This study aims to assess the impacts of melatonin as the complementary treatments on oxidative stress agents and inflammasome activation in patients with COVID-19. Melatonin supplement (9 mg daily, orally) was provided for the patients hospitalized with a COVID-19 analysis for 14 days. For measuring IL-10, IL-1β, and TNF-α cytokines and malondialdehyde (MDA), nitric oxide (NO), and superoxide dismutase (SOD) level and the expression of CASP1 and ASC genes, blood samples were gathered from the individuals at the start and termination of the therapy. Our findings indicated that melatonin is used as a complementary treatment to reduce the levels of TNF-α and IL-1β cytokines, MDA, and NO levels in COVID-19 patients and significantly increase SOD level, however, the levels of IL-10 cytokine possesses no considerable changes. The findings revealed that genes of CASP1 and ASC were dysregulated by melatonin regulating the inflammasome complex. Based on the findings of the current study, it is found that melatonin can be effective as a medicinal supplement in decreasing the inflammasome multiprotein complex and oxidative stress along with beneficial impacts on lung cytokine storm of COVID-19 patients.