•TIGIT and HIF-1α dual-blocking significantly reduced tumor invasion, colony formation, and tumor growth.•TIGIT and HIF-1α co-suppression revoked anti-tumor immune responses and improved survival ...time in murine tumor models.•TIGIT and HIF-1α could be used as a novel treatment strategy against colorectal and breast cancer.
T-cell immunoglobulin and ITIM domain (TIGIT) is an immune checkpoint that is overexpressed on both immune cells and some cancer cells. TIGIT can alter the anti-tumor responses inside the tumor microenvironment. Hypoxia-inducible factor 1-alpha (HIF-1α) plays a significant role in the TME and involves suppressing the anti-tumor responses. Under hypoxic conditions, HIF-1α can enhance the expression of different immune checkpoints. Accordingly, hypoxic TME and TIGIT overexpression cause cancer development. Thus, we decided to inhibit tumor cell expansion by inhibiting TIGIT and HIF-1α molecules and discovering the relationship between TIGIT and HIF-1α.
In this research, we utilized superparamagnetic iron oxide-based NPs (SPIONs) combined with chitosan lactate (CL) and folic acid (FA) nanoparticles (NPs) loaded with TIGIT-siRNA and HIF-1α- siRNA for suppressing TIGIT and HIF-1α in tumor cells and evaluated the consequences of this treatment strategy on tumor growth, apoptosis, and metastasis.
The results showed that cancer cells treated with TIGIT and HIF-1α siRNA-loaded SPIONs-CL-FA NPs, strongly suppressed the TIGIT and HIF-1α expression, colony formation ability, angiogenesis, and the growth rate of cancer cells.
Present data suggest the combination treatment of TIGIT and HIF-1α as a novel treatment strategy against colorectal and breast cancer, but more researches are required to realize the complete role of TIGIT and HIF-1α inside the TME.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Thermodynamic and kinetic parameters, such as enthalpy, entropy, and free energy, are crucial in evaluating enzyme stability and activity. These parameters, including the free energy of activation ...(ΔG
) and the Gibbs free energy of inactivation (ΔG*), are important for predicting energy requirements and reaction rates. However, relying solely on these parameters is insufficient in selecting an enzyme for industrial processes. Numerous studies have explored the measurement of thermodynamic parameters for proteases. Unfortunately, some of the definitions and calculations of key parameters such as ΔG
, ΔG*, and substrate-binding free energy have contained significant errors. In this study, these mistakes have been addressed and corrected. Additionally, a new parameter called δ, defined as the difference between ΔG* and ΔG
, has been introduced for the first time. It is argued that δ provides a more reliable measure for predicting the potential industrial application of enzymes. The highest calculated value for δ was found to be 39.6 kJ·mol
at 55 °C. Furthermore, this study also presents a comprehensive collection and determination of all thermodynamic and kinetic parameters for proteases, providing researchers and professionals in the field with a valuable resource to compare and understand the relationships between these parameters and the industrial potential of enzymes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Following various immunotherapies, lack of proper anti-tumor immune responses is considered a significant problem in novel cancer therapeutic approaches. The expression of inhibitory checkpoint ...molecules on tumor-infiltrating T cells is one of the main reasons for the ineffectiveness of various immunotherapies. Therefore, we decided to inhibit two of the most important immune checkpoints expressed on tumor-associated T cells, PD-1 and A2aR. Ligation of PD-1 with PD-L1 and A2aR with adenosine significantly suppress T cell responses against tumor cells. Whitin tumors, specific inhibition of these molecules on T cells is of particular importance for successful immunotherapy as well as the elimination of treatment-associated side-effects. Thus, in this study, superparamagnetic iron oxide (SPION) nanoparticles (NPs) were covered by chitosan lactate (CL), functionalized with TAT peptide, and loaded with siRNA molecules against PD-1 and A2aR. Appropriate physicochemical properties of the prepared NPs resulted in efficient delivery of siRNA to tumor-derived T cells and suppressed the expression of A2aR and PD-1, ex vivo. T cell functions such as cytokine secretion and proliferation were considerably enhanced by the downregulation of these molecules which led to an increase in their survival time. Interestingly, treatment of CT26 and 4T1 mouse tumors with siRNA-loaded NPs not only inhibited tumor growth but also markedly increased anti-tumor immune responses and survival time. The results strongly support the efficacy of SPION-CL-TAT NPs loaded with anti-PD-1/A2aR siRNAs in cancer therapy and their further development for cancer patients in the near future.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Clostridium perfringens (C. perfringens) is a serious anaerobic enteric pathogen causing necrotic enteritis (NE) in broiler chickens. Following the ban on antibiotics as growth promoters in animal ...feedstuffs, there has been a remarkable rise in occurrence of NE which resulted in considering alternative approaches, particularly vaccination. The objective of this work was to evaluate the recombinant Lactobacillus casei (L. casei) expressing the C-terminal domain of α-toxin from C. perfringens as a potential probiotic-based vaccine candidate to immunize the broiler chickens against NE.
The broiler chickens immunized orally with recombinant vaccine strain were significantly protected against experimental NE challenge, and developed specific serum anti-α antibodies. Additionally, the immunized birds showed higher body weight gains compared with control groups during the challenge experiment.
The current study showed that oral immunization of broiler chickens with a safe probiotic-based vector vaccine expressing α-toxin from C. perfringens could provide protective immunity against NE in birds.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•Cellular immunity performs a critical role in immune responses versus SARS-CoV-2.•Increased Th17 and Th1 correlates with disease progression in SARS-CoV-2 patients.•Treg and Th2 cells are ...significantly decreased in patients with severe SARS-CoV-2.•Exhausted T cells are markedly increased in ICU hospitalized SARS-CoV-2 patients.
In various pathological conditions, cellular immunity plays an important role in immune responses. Amongimmunecells, T lymphocytes pdomotecellular and humoralresponses as well as innate immunity. Therefore, careful investigation of these cells has a significant impact on accurate knowledge in COVID-19diseasepathogenesis. In current research, the frequency and function of various T lymphocytes involved in immune responses examined in SARS‐CoV-2 patients with various disease severity compared to normal subjects. In order to make an accurate comparison among patients with various disease severity, this study was performed on asymptomatic recovered cases (n = 20), ICU hospitalized patients (n = 30), non-ICU hospitalized patients (n = 30), and normal subjects (n = 20). To precisely evaluate T cells activity following purification, their cytokine secretion activity was examined. Similarly, immediately after purification of Treg cells, their inhibitory activity on T cells was investigated. The results showed that COVID-19 patients with severe disease (ICU hospitalized patients) not only had a remarkable increase in Th1 and Th17 but also a considerable decrease in Th2 and Treg cells. More importantly, as the IL-17 and IFN-γ secretion was sharply increased in severe disease, the secretion of IL-10 and IL-4 was decreased. Furthermore, the inhibitory activity of Treg cells was reduced in severe disease patients in comparison to other groups. In severe COVID-19 disease, current findings indicate when the inflammatory arm of cellular immunity is significantly increased, a considerable reduction in anti-inflammatory and regulatory arm occurred.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Corneal transplantation is considered a convenient strategy for various types of corneal disease needs. Even though it has been applied as a suitable solution for most corneal disorders, patients ...still face several issues due to a lack of healthy donor corneas, and rejection is another unknown risk of corneal transplant tissue. Corneal tissue engineering (CTE) has gained significant consideration as an efficient approach to developing tissue-engineered scaffolds for corneal healing and regeneration. Several approaches are tested to develop a substrate with equal transmittance and mechanical properties to improve the regeneration of cornea tissue. In this regard, bioprinted scaffolds have recently received sufficient attention in simulating corneal structure, owing to their spectacular spatial control which produces a three-cell-loaded-dimensional corneal structure. In this review, the anatomy and function of different layers of corneal tissue are highlighted, and then the potential of the 3D bioprinting technique for promoting corneal regeneration is also discussed.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Applying biological macromolecule like silk fibroin (SF) is a promising material for corneal tissue engineering. However, designing an appropriate tissue-like construct to compensate the shortages of ...traditional routes are still challenging. SF besides possessing biocompatibility and transparency, the biomaterial should be mechanically strong. In the present study, a hybrid scaffold composed of poly-ε-caprolactone (PCL)-silk fibroin (SF) is fabricated through electro spinning technique. The aligned and non-aligned PCL-SF scaffolds with various weight ratios are fabricated. The results reveal that the addition of SF yields the scaffolds with more uniform and aligned structure. The ultimate tensile strength and Young's modulus of aligned and non-aligned PCL-SF (60:40 and 50:50) fibers are in an acceptable range for cornea applications. It is noteworthy that the aligned PCL-SF (60:40 and 50:50) scaffolds have more transparency, hydrophilicity, water uptake, and in vitro degradation rate than the other scaffolds. The cell compatibility results show that human stromal keratocyte cells are attached and proliferated on the aligned and non-aligned PCL-SF scaffolds. The overall results recommend that PCL-SF (60:40 and 50:50) scaffolds have a great potential for human corneal stromal regeneration.
•Polycaprolactone/silk fibroin electrospun scaffolds with various weight ratios were fabricated and characterized.•The ultimate tensile strength and Young's modulus of PCL-SF fibers are in an acceptable range for cornea applications.•The aligned electrospun fibers had better physico-chemical properties compare with random fibers.•Aligned structure directly affects the arrangement and aggregation of cells in a positive way.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Natural bone constitutes a complex and organized structure of organic and inorganic components with limited ability to regenerate and restore injured tissues, especially in large bone defects. To ...improve the reconstruction of the damaged bones, tissue engineering has been introduced as a promising alternative approach to the conventional therapeutic methods including surgical interventions using allograft and autograft implants. Bioengineered composite scaffolds consisting of multifunctional biomaterials in combination with the cells and bioactive therapeutic agents have great promise for bone repair and regeneration. Cellulose and its derivatives are renewable and biodegradable natural polymers that have shown promising potential in bone tissue engineering applications. Cellulose-based scaffolds possess numerous advantages attributed to their excellent properties of non-toxicity, biocompatibility, biodegradability, availability through renewable resources, and the low cost of preparation and processing. Furthermore, cellulose and its derivatives have been extensively used for delivering growth factors and antibiotics directly to the site of the impaired bone tissue to promote tissue repair. This review focuses on the various classifications of cellulose-based composite scaffolds utilized in localized bone drug delivery systems and bone regeneration, including cellulose-organic composites, cellulose-inorganic composites, cellulose-organic/inorganic composites. We will also highlight the physicochemical, mechanical, and biological properties of the different cellulose-based scaffolds for bone tissue engineering applications.
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•Cellulose and its derivatives are renewable and biodegradable natural polymers that with great potential for bone tissue engineering.•Cellulose-based materials can be used various therapeutics directly to the bone to achieve bone regeneration.•Bioinks made of cellulose-based materials hold great promise to develop patient specific solutions for bone repair using 3D printing.•Challenges associated with inaccuracies in existing preclinical models, sterilization regulatory barriers still need to be addressed before clinical translation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Corneal transplantation has been applied mainly for common corneal diseases. Although it has been used formerly as a common treatment, it suffers some shortcomings such as the lack of suitable donors ...and the rejection of the tissue by the host immune system. Recently, tissue engineering has been considered as a good replacement for corneal transplantation due to its high range of applicability. For this purpose, a variety of materials have been investigated to facilitate corneal regeneration. Polycaprolactone (PCL), apart from being a biodegradable and biocompatible polyester, is cost efficient, readily available and an easy to modify polymer. Therefore, PCL is presently a promising material with an enormous variety of tissue engineering applications. PCL has adjustable mechanical strength, along with biological properties and physiochemical state that allow it to withstand mechanical, chemical and physical insults without significant loss of its properties. This paper reviews the recent progress of using PCL in corneal tissue engineering.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
In the present study, to advance the skin tissue regeneration process, aspirin (AS)-loaded polycaprolactone (PCL) and maltodextrin (MD) composite nanofiber was prepared via electrospinning technique. ...The results showed that the composite had more uniform nanofibers and the mean diameter of the nanofibers was reduced from 186 to 96 nm experimentally with increasing AS percentages. Biological evaluations proved that L929 fibroblast cells on the PCL/MD with 2% AS had better cell adhesion and proliferation. The overall results introduce that 2% AS incorporated in the PCL/MD electrospun nanofibers can be applied as a promising candidate for further studies toward skin tissue regeneration.
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BFBNIB, DOBA, GIS, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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