Microfluidic System Consisting of a Magnetic 3D-Printed Microchannel Filter for Isolation and Enrichment of Circulating Tumor Cells Targeted by Anti-HER2/MOF@Ferrite Core-Shell Nanostructures: A Theranostic CTC Dialysis System.

Low number of circulating tumor cells (CTCs) in the blood samples and time-consuming properties of the current CTC isolation methods for processing a small volume of blood are the biggest obstacles to CTC usage in practice. Therefore, we aimed to design a CTC dialysis system with the ability to process cancer patients' whole blood within a reasonable time. Two strategies were employed for developing this dialysis setup, including (i) synthesizing novel in situ core-shell Cu ferrites consisting of the Cu-CuFe2O4 core and the MIL-88A shell, which are targeted by the anti-HER2 antibody for the efficient targeting and trapping of CTCs; and (ii) fabricating a microfluidic system containing a three-dimensional (3D)-printed microchannel filter composed of a polycaprolactone/Fe3O4 nanoparticle composite with pore diameter less than 200 µm on which a high-voltage magnetic field is focused to enrich and isolate the magnetic nanoparticle-targeted CTCs from a large volume of blood. The system was assessed in different aspects including capturing the efficacy of the magnetic nanoparticles, CTC enrichment and isolation from large volumes of human blood, side effects on blood cells, and the viability of CTCs after isolation for further analysis. Under the optimized conditions, the CTC dialysis system exhibited more than 80% efficacy in the isolation of CTCs from blood samples. The isolated CTCs were viable and were able to proliferate. Moreover, the CTC dialysis system was safe and did not cause side effects on normal blood cells. Taken together, the designed CTC dialysis system can process a high volume of blood for efficient dual diagnostic and therapeutic purposes.

Role of the Probe Sequence/Structure in Developing an Ultra-Efficient Label-Free COVID-19 Detection Method Based on Competitive Dual-Emission Ratiometric DNA-Templated Silver Nanoclusters as Single Fluorescent Probes.

We report the development of a label-, antibody-, enzyme-, and amplification-free ratiometric fluorescent biosensor for low-cost and rapid (less than 12 min) diagnosis of COVID-19 from isolated RNA samples. The biosensor is designed on the basis of cytosine-modified antisense oligonucleotides specific for either N gene or RdRP gene that can form silver nanoclusters (AgNCs) with both green and red emission on an oligonucleotide via a one-step synthesis process. The presence of the target RNA sequence of SARS-CoV-2 causes a dual-emission ratiometric signal transduction, resulting in a limit of detection of 0.30 to 10.0 nM and appropriate linear ranges with no need for any further amplification, fluorophore, or design with a special DNA fragment. With this strategy, five different ratiometric fluorescent probes are designed, and how the T/C ratio, the length of the stem region, and the number of cytosines in the loop structure and at the 3' end of the cluster-stabilizing template can affect the biosensor sensitivity is investigated. Furthermore, the effect of graphene oxide (GO) on the ratiometric behavior of nanoclusters is demonstrated and the concentration-/time-dependent new competitive mechanism between aggregation-caused quenching (ACQ) and aggregation-induced emission enhancement (AIE) for the developed ssDNA-AgNCs/GO nanohybrids is proposed. Finally, the performance of the designed ratiometric biosensor has been validated using the RNA extract obtained from more than 150 clinical samples, and the results have been confirmed by the FDA-approved reverse transcription-polymerase chain reaction (RT-PCR) diagnostic method. The diagnostic sensitivity and specificity of the best probe is more than >90%, with an area under the receiver operating characteristic (ROC) curve of 0.978.

Biodegradable and biocompatible subcutaneous implants consisted of pH-sensitive mebendazole-loaded/folic acid-targeted chitosan nanoparticles for murine triple-negative breast cancer treatment.

BACKGROUND: Mebendazole (MBZ) is a well-known anti-parasite drug with significant anti-cancer properties. However, MBZ exhibits low solubility, limited absorption efficacy, extensive first-pass effect, and low bioavailability. Therefore, multiple oral administration of high dose MBZ is required daily for achieving the therapeutic serum level which can cause severe side effects and patients' non-compliance. METHOD: In the present study, MBZ-loaded/folic acid-targeted chitosan nanoparticles (CS-FA-MBZ) were synthesized, characterized, and used to form cylindrical subcutaneous implants for 4T1 triple-negative breast tumor (TNBC) treatment in BALB/c mice. The therapeutic efficacy of the CS-FA-MBZ implants was investigated after subcutaneous implantation in comparison with Control, MBZ (40 mg/kg, oral administration, twice a week for 2 weeks), and CS-FA implants, according to 4T1 tumors' growth progression, metastasis, and tumor-bearing mice survival time. Also, their biocompatibility was evaluated by blood biochemical analyzes and histopathological investigation of vital organs. RESULTS: The CS-FA-MBZ implants were completely degraded 15 days after implantation and caused about 73.3%, 49.2%, 57.4% decrease in the mean tumors' volume in comparison with the Control (1050.5 ± 120.7 mm3), MBZ (552.4 ± 76.1 mm3), and CS-FA (658.3 ± 88.1 mm3) groups, respectively. Average liver metastatic colonies' number per microscope field at the CS-FA-MBZ group (2.3 ± 0.7) was significantly (P < 0.05) lower than the Control (9.6 ± 1.7), MBZ (5.0 ± 1.5), and CS-FA (5.2 ± 1) groups. In addition, the CS-FA-MBZ treated mice exhibited about 52.1%, 27.3%, and 17% more survival days after the cancer cells injection in comparison with the Control, MBZ, and CS-FA groups, respectively. Moreover, the CS-FA-MBZ implants were completely biocompatible based on histopathology and blood biochemical analyzes. CONCLUSION: Taking together, CS-FA-MBZ implants were completely biodegradable and biocompatible with high therapeutic efficacy in a murine TNBC model.

Spirulina extract enriched for Braun-type lipoprotein (Immulina®) for inhibition of 4T1 breast tumors' growth and metastasis.

Spirulina platensis extracts have exhibited considerable anti-cancer effects. To investigate the efficacy of the Spirulina extract enriched for Braun-type lipoprotein (Immulina®) for breast cancer treatment, 4T1 breast tumor-bearing mice were treated with 40 mg/kg Immulina® daily and the tumors' growth and metastasis were assessed. Also, CD4, CD8, and CD56 staining were performed to investigate the Immulina® effect on the immune cells' recruitment to the tumors by immunohistochemistry. Immulina® could significantly (P < 0.001) inhibit 4T1 breast tumors' growth. Immulina®-treated group exhibited a 63% decrease in the tumors' volume in comparison with control (P < 0.001). Also, Immulina® could significantly (P < 0.001) decrease metastatic burden at the vital organs as 68% and 61% decrease in the liver and lungs metastatic colonies were observed, respectively. Also, Immulina® could increase mean survival time of the tumor-bearing mice for 29 days. The Spirulina-treated mice tumors contained significantly more infiltrated NK, CD4+, and CD8+ T lymphocytes in comparison with control. Taking together, Immulina® can be a safe anti-cancer supplement with the ability to cause direct apoptosis to the cancer cells and activate the immune system against tumor. This supplement with natural origin seems to have bright future to help breast cancer patients.

Utilizing 808 nm laser for sensitizing of melanoma tumors to megavoltage radiation therapy.

Melanotic melanoma has high content of melanin and laser can destroy melanin-containing cells through thermal effect. In this study, the therapeutic effect of 808 nm laser therapy was investigated on B16-F10 melanoma tumor growth and tumor-bearing mice survival time. In addition, as laser can destroy melanin as the main cause of melanoma radioresistance, the effect of laser administration to enhance radiation therapy efficacy at B16-F10 cancer cells was evaluated in vitro and in vivo. Laser therapy (1 W/cm2 × 4 min) could cause significant (P < 0.05) inhibition of melanoma tumors' growth (~ 61%) and about three times increase of the tumor-bearing mice survival time in comparison with no-treatment group. In addition, the mice which were treated with 1 W/cm2 × 4 min laser administration plus 6 Gy megavoltage radiation therapy exhibited ~ 68% lesser tumors' volume and 27 days increase of survival time in comparison with 6 Gy irradiated tumor-bearing mice. Also, significantly higher (P < 0.05) tumor necrosis percentage was observed at the histopathological slides of 1 W/cm2 × 4 min laser + RT treated mice tumors (57 ± 12%) in comparison with radiation therapy group (31 ± 10%). Therefore, not only laser therapy can inhibit melanoma tumors' growth per se but also its combination with radiation therapy can cause a significant enhancement of radiation therapy efficacy. The laser administration can be used as a radiosensitizing method for melanotic melanoma radiation therapy.

Prolactin receptor expression as a novel prognostic biomarker for triple negative breast cancer patients.

Prolactin receptor (PRLR) is a novel emerging prognostic biomarker in different cancers, especially in breast cancer. However, there is limited information about the association of PRLR expression and triple-negative breast cancers (TNBC) prognosis. In this study, 80 TNBC patients were evaluated for PRLR expression by immunohistochemistry. The correlation of PRLR expression with clinicopathological features, patient recurrence, and survival was investigated. PRLR expression was considered positive if >10% of tumor cells were stained. The Fisher's exact test was used to analyze PRLR expression relation with the clinicopathological parameters. Survival distribution was estimated by the Kaplan-Meier method. Positive immunoreactivity for PRLR was observed in 50 out of 80 (62%) specimens. Although expression of PRLR was associated with TNBC patients' stage, no-correlation was observed between its expression and tumor size, grade, lymph node status, and Ki-67 expression. In addition, patients with positive expression of PRLR exhibited lower recurrence (P = 0.0027) and higher overall survival (P = 0.0285) in comparison with negative expression group. In multivariate analyses, positive expression of PRLR was an independent prognostic marker for lower recurrence (P < 0.001) and higher overall survival (P < 0.001). Therefore, PRLR plays a crucial role in TNBC and has to be considered as an independent prognostic biomarker for TNBC patients.

Ultra-small but ultra-effective: Folic acid-targeted gold nanoclusters for enhancement of intracranial glioma tumors' radiation therapy efficacy.

The aim of the present study is to investigate folic acid and BSA decorated gold nanoclusters (FA-AuNCs) effect on the enhancement of intracranial C6 glioma tumors radiation therapy (RT) efficacy. Inductively coupled plasma optical emission spectrometry (ICP-OES) measurements exhibited about 2.5 times more FA-AuNCs uptake by C6 cancer cells (32.8 ng/106 cells) than the normal cells. FA-AuNCs had significantly higher concentration in the brain tumors (8.1 µg/mg) in comparison with surrounding normal brain tissue (4.3 µg/mg). Moreover, FA-AuNCs exhibited dose enhancement factor (DEF) of 1.6. The glioma-bearing rats' survival times were almost doubled at radiation therapy + FA-AuNCs (25.0 ±â€¯1.5 days) in comparison with no-treatment group (12.8 ±â€¯0.7 days). The Ki-67 labeling index was 48.89% ±â€¯9.93 for control, 29.98% ±â€¯8.32 for RT, and 11.53% ±â€¯7.65 for RT + FA-AuNCs. Therefore, FA-AuNCs can be effective radiosensitizers for intracranial glioma tumors RT.

Design, Synthesis and Molecular Docking Studies of Some Tetrahydropyrimidine Derivatives as Possible Fascin Inhibitors.

Eight derivatives of tetrahydropyrimidine scaffold were designed and prepared as hybrid compounds possessing the structural features of both monastrol as an anticancer drug and nifedipine as a fascin blocking agent. All of the compounds were evaluated for their cytotoxic potency and the ability to inhibit 4T1 breast cancer cells migration. Then, they were investigated in silico for their ability to inhibit the fascin protein using molecular docking simulation. The most potent compound was 4d and the weakest one was 4a according to the in vitro cytotoxicity assay. The corresponding IC50 values were 193.70 and 248.75 µm, respectively. The least cytotoxic compound (4a) was one of the strongest ones in binding to the fascin binding site according to the molecular docking results. 4a and 4e inhibited the 4T1 cells migration better than other compounds. They were more potent than nifedipine in inhibiting the migration process. In silico studies proved 4h to be the most potent fascin inhibitor in terms of ΔGbind although it was not inhibiting migration. The controversy between the in vitro and in silico results may cancel the theory of the involvement of the fascin inhibition in the migration inhibition. However, the considerable antimigratory effects of some of the synthesized compounds encourage performing further in vivo experiments to introduce novel tumor metastasis inhibitors.

Challenges and Opportunities of Using Fluorescent Metal Nanocluster-Based Colorimetric Assays in Medicine.

Development of rapid colorimetric methods based on novel optical-active metal nanomaterials has provided methods for the detection of ions, biomarkers, cancers, etc. Fluorescent metal nanoclusters (FMNCs) have gained a lot of attention due to their unique physical, chemical, and optical properties providing numerous applications from rapid and sensitive detection to cellular imaging. However, because of very small color changes, their colorimetric applications for developing rapid tests based on the naked eye or simple UV-vis absorption spectrophotometry are still limited. FMNCs with peroxidase-like activity have significant potential in a wide variety of applications, especially for point-of-care diagnostics. In this review, the effect of using various capping agents and metals for the preparation of nanoclusters in their colorimetric sensing properties is explored, and the synthesis and detection mechanisms and the recent advances in their application for ultrasensitive chemical and biological analysis regarding human health are highlighted. Finally, the challenges that remain as well as the future perspectives are briefly discussed. Overcoming these limitations will allow us to expand the nanocluster's application for colorimetric diagnostic purposes in medical practice.

An unusual presentation of metastatic prostate cancer in a 44-year-old man: A case report and review of the literature.

Prostate cancer is one of the two most common non-cutaneous cancers in men. Its presentation might be with unusual symptoms and cause the wrong initial diagnosis. This case report discusses a rare neurologic manifestation of advanced metastatic cancer in a low-risk man. He had been receiving treatment for multiple sclerosis incorrectly due to unusual manifestations such as claudication and pelvic, leg, and shoulder pain. The patient underwent a whole-body bone scan and then a transrectal ultrasound-guided biopsy, which confirmed metastatic prostate cancer with a Gleason score between 7/10 and 10/10 in all samples. Following treatment with chemotherapeutic injections (docetaxel), luteinizing hormone-releasing hormone (LHRH) analogous (Zoladex), and testosterone-suppressing tablets (abiraterone), the disease has been under control and prostate-specific antigen (PSA) level has decreased significantly. The most common sites of metastasis are regional lymph nodes, bones, and lungs. However, there are reports about the spread of this type of cancer to other parts of the body. Although most patients are diagnosed when the tumor is localized to the prostate, in about 25% of patients, the disease is diagnosed when metastasis has occurred. Some markers can assist physicians in the diagnosis of this disease, such as the Prostate Health Index and the 4 K score. Key Clinical Message: The diagnosis of prostate cancer should be considered in all age ranges of adult men. The long-distance metastasis might cause unusual presentations of the disease, such as neurologic, musculoskeletal, and dermatologic symptoms and signs far from the origin of the cancer, before genitourinary manifestations. It is crucial to keep the diagnosis of prostate cancer in mind for men with suggestive signs and symptoms that are not usually detected in this disease.

Veillonella parvula as an anaerobic lactate-fermenting bacterium for inhibition of tumor growth and metastasis through tumor-specific colonization and decrease of tumor's lactate level.

High tumor's lactate level directly associates with high tumor growth, metastasis, and patients' poor prognosis. Therefore, many studies have focused on the decrease of tumor's lactate as a novel cancer treatment. In the present study for the first time, a strictly anaerobic lactate-fermenting bacterium, Veillonella parvula, was employed for the decrease of tumor's lactate level. At first, 4T1 breast tumor-bearing BALB/c mice were administered with 106 V. parvula bacteria intravenously, orally, intraperitoneally, and intratumorally. Then, the bacteria biodistribution was evaluated. The best administration route according to tumor colonization was selected and its safety was assessed. Then, the therapeutic effect of V. parvula administration through the best route was investigated according to 4T1 murine breast tumor's growth and metastasis in vivo. In addition, histopathological and immunohistochemistry evaluations were done to estimate microscopic changes at the inner of the tumor and tumor's lactate level was measured after V. parvula administration. V. parvula exhibited considerable tumor-targeting and colonization efficacy, 24 h after intravenous administration. Normal organs were free of the bacteria after 72 h and no side effect was observed. Tumor colonization by V. parvula significantly decreased the tumors' lactate level for about 46% in comparison with control tumors which caused 44.3% and 51.6% decline (P < 0.05) in the mean tumors' volume and liver metastasis of the treatment group in comparison with the control group, respectively. The treatment group exhibited 35% inhibition in the cancer cell proliferation in comparison with the control according to the Ki-67 immunohistochemistry staining. Therefore, intravenous administration of V. parvula is a tumor-specific and safe treatment which can significantly inhibit tumors' growth and metastasis by decreasing the tumor lactate level.

Bioelectrocatalytic Activity of One-Dimensional Porous Pt Nanoribbons for Efficient Inhibition of Tumor Growth and Metastasis.

Designing and synthesizing one-dimensional porous Pt nanocrystals with unique optical, electrocatalytic, and theranostic properties are gaining lots of attention, especially to overcome the challenges of tumor recurrence and resistance to platinum-based chemotherapy. Herein, we represented an interesting report of a one-step and facile strategy for synthesizing multifunctional one-dimensional (1D) porous Pt nanoribbons (PtNRBs) with highly efficient therapeutic effects on cancer cells based on inherent electrocatalytic activity. The critical point in the formation of luminescent porous PtNRBs was the use of human hemoglobin (Hb) as a shape-regulating, stabilizing, and reducing agent with facet-specific domains on which fluorescent platinum nanoclusters at first are aggregated by aggregation-induced emission phenomena (AIE) and then crystallized into contact and penetration twins, as intermediate products, followed by shaping of the final luminescent porous ribbon nanomaterials, owing to oriented attachment association via the Ostwald ripening mechanism. From a medical point of view, the key strategy for effective cancer therapy occured via using low-dosage ethanol in the presence of electroactive porous PtNRBs based on intracellular ethanol oxidation-mediated reactive oxygen species (ROS) generation. The role of heme groups of Hb, as electrocatalytically active centers, was successfully demonstrated in both kinetically controlled anisotropic growth of NRBs for slowing down the reduction of Pt(II) followed by oligomerization of Pt(II)-Hb complexes via platinophilic interactions as well as electrocatalytic ethanol oxidation for therapy. Interestingly, hyaluronic acid-targeted (HA) Hb-PtNRB in the presence of low-dose ethanol caused extraordinary arrest of tumor growth and metastasis with no recurrence even after the treatment course stopped, which caused elongation of tumor-bearing mice survival. HA/Hb-PtNRB was completely biocompatible and exhibited high tumor-targeting efficacy for fluorescent imaging of breast tumors. Therefore, the synergistic electrocatalytic activity of PtNRBs is presented as an efficient and safe cancer theranostic method for the first time.

Potential anti-cancer effects of hibernating common carp (Cyprinus carpio) plasma on B16-F10 murine melanoma: In vitro and in vivo studies.

Melanoma is the major type of skin cancer, which its treatment is still a challenge in the world. In recent years, interest in hibernation-based therapeutic approaches for various biomedical applications has been increased. Many studies indicated that some factors in the blood plasma of hibernating animals such as alpha-2-macroglobulin (A2M) cause anti-proliferative effects. Considering that, the present study was conducted to investigate the anti-cancer effects of hibernating common carp plasma (HCCP) on murine melanoma (B16-F10) in vitro and in vivo. The effect of HCCP on cell viability, migration, apoptosis rate, and cell cycle distribution of B16-F10 cells, tumor growth, and rate of survival were evaluated. To investigate the role of A2M in the anti-cancer effects of HCCP, the gene of interest and proteins in HCCP and non-hibernating common carp plasma (NHCCP) were evaluated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assay as well as sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and mass spectrometry analysis. Based on our findings, HCCP significantly decreased B16-F10 cell viability. Moreover, HCCP caused morphological alternations, inhibition of migration, induction of apoptosis, and significantly induced the cell cycle arrest at the G2/M phase. In addition, A2M level was significantly increased in HCCP compared with NHCCP. Taken together, our findings suggested that HCCP had the potential to be a promising novel therapeutic target for cancer treatment because of its anti-cancer properties.

Highly improved pH-Responsive anticancer drug delivery and T2-Weighted MRI imaging by magnetic MOF CuBTC-based nano/microcomposite.

Cu-BTC framework has received a considerable attention in recent years as a drug carrier candidate for cancer treatment due to its unique structural properties and promising biocompatibility. However, its intrinsic deficiency for medical imaging potentially limits its bioapplications; To address this subject, a magnetic nano/microscale MOF has been successfully fabricated by introducing Fe3O4 nanoparticles as an imaging agent into the porous isoreticular MOF [Cu3(BTC)2] as a drug carrier. The synthesized magnetic MOFs exhibits a high loading capacity (40.5%) toward the model anticancer DOX with an excellent pH-responsive drug release. The proposed nanocomposite not only possesses large surface area, high magnetic response, large mesopore volume, high transverse relaxivity (r 2) and good stability but also exhibits superior biocompatibility, specific tumor cellular uptake, and significant cancer cell viability inhibitory effect without any targeting agent. It is expected that the synthesized magnetic nano/microcomposite may be used for clinical purposes and can also serve as a platform for photoactive antibacterial therapy ae well as pH/GSH/photo-triple-responsive nanocarrier.

In vitro and in vivo anti-cancer effects of hibernating common carp (Cyprinus carpio) plasma on metastatic triple-negative breast cancer.

Uncontrollable proliferation is a hallmark of cancer cells. Cell proliferation and migration are significantly depressed during hibernation state. Many studies believe some factors in the plasma of hibernating animals cause these effects. This study aimed to assess the anti-cancer effects of hibernating common carp (Cyprinus carpio) plasma on 4T1 cancer cells in vitro and in vivo. The effect of hibernating plasma on cell viability, morphology, migration, apoptosis rate, and cell cycle distribution of 4T1 cells was investigated in vitro and in vivo. Hibernating plasma at a concentration of 16 mg/ml significantly reduced the viability of 4T1 cancer cells, without any toxicity on L929 normal fibroblast cells. It could change the morphology of cancer cells, induced apoptosis and cell cycle arrest at the G2/M phase, and inhibited migration. Furthermore, intratumoral injection of hibernating plasma (200 µl, 16 mg/ml) in the tumor-bearing mice caused a significant inhibition of 4T1 breast tumors volume (46.9%) and weight (58.8%) compared with controls. A significant decrease in the number of metastatic colonies at the lungs (80%) and liver (52.8%) of hibernating plasma-treated animals was detected which increased the survival time (21.9%) compared to the control groups. Immunohistochemical analysis revealed a considerable reduction in the Ki-67-positive cells in the tumor section of the hibernating plasma-treated animals compared with controls. Taken together, the SDS-PAGE and mass spectrometry analysis indicated the alpha-2-macroglobulin level in the hibernating fish plasma was significantly increased. It could exert an anti-cancer effect on breast cancer cells and suggested as a novel cancer treatment strategy.

An in vitro and in vivo study of PCL/chitosan electrospun mat on polyurethane/propolis foam as a bilayer wound dressing.

In the current study, we fabricated a bilayer wound dressing consisting of an electrospun poly-ε-caprolactone/chitosan (PCL/CS) fibrous mat as the sublayer and a polyurethane (PU) foam coated with ethanolic extract of propolis (EEP) as the top layer. By blending the solutions of PCL and CS, we fabricated an electrospun mat consisting of bead-free and uniform nanofibers with enhanced hydrophilicity, swelling ratio, and degradation properties. To further enhance the mechanical and antibacterial properties, we electrospun the PCL/CS solution on a PU foam coated with EEP to fabricate the PCL/CS-PU/EEP bilayer wound dressing. Furthermore, the PCL/CS-PU/EEP bilayer wound dressing demonstrated enhanced cell compatibility and healing properties through in vitro and in vivo studies. Therefore, the PCL/CS-PU/EEP bilayer wound dressing offers great potential to be used as a wound dressing because of its suitable mechanical properties, swelling profile, antibacterial activity, biocompatibility, and wound healing properties.

A 3D macroporous and magnetic Mg2SiO4-CuFe2O4 scaffold for bone tissue regeneration: Surface modification, in vitro and in vivo studies.

Macroporous scaffolds with bioactivity and magnetic properties can be a good candidate for bone regeneration and hyperthermia. In addition, modifying the surface of the scaffolds with biocompatible materials can increase their potential for in vivo applications. Here, we developed a multifunctional nanocomposite Mg2SiO4-CuFe2O4 scaffold for bone regeneration and hyperthermia. The surface of scaffold was coated with various concentrations of poly-3-hydroxybutyrate (P3HB, 1-5% (w/v)). It was observed that 3% (w/v) of P3HB provided a favorable combination of porosity (79 ± 2.1%) and compressive strength (3.2 ± 0.11 MPa). The hyperthermia potential of samples was assessed in the presence of various magnetic fields in vitro. The coated scaffolds showed a lower degradation rate than the un-coated one up to 35 days of soaking in simulated biological medium. Due to the porous and specific morphology of P3HB, it was found that in vitro bioactivity and cell attachment were increased on the scaffold. Moreover, it was observed that the P3HB coating improved the cell viability, alkaline phosphatase activity, and mineralization of the scaffold. Finally, we studied the bone formation ability of the scaffolds in vivo, and implanted the developed scaffold in the rat's femur for 8 weeks. Micro-computed tomography results including bone volume fraction and trabecular thickness exhibited an improvement in the bone regeneration of the coated scaffold compared to the control. The overall results of this study introduce a highly macroporous scaffold with multifunctional performance, noticeable ability in bone regeneration, and hyperthermia properties for osteosarcoma.

Multifunctional Gold Helix Phototheranostic Biohybrid That Enables Targeted Image-Guided Photothermal Therapy in Breast Cancer.

The preparation of multifunctional smart theranostic systems is commonly achieved through complicated strategies, limiting their biomedical applications. Spirulina platensis (SP) microalgae, as a natural helix with some of the intrinsic theranostic functionalities (e.g., fluorescent and photosensitizer pigments), not only facilitates the fabrication process but also guarantees their biosafety for clinical applications. Herein, the helical architecture of gold nanoparticles (AuNPs) based on a SP biotemplate was engineered as a safe, biodegradable, and tumor-targeted biohybrid for imaging-guided photothermal therapy (PTT) to combat triple-negative breast cancer. The quasi-spherical AuNPs were embedded throughout the SP cell (Au-SP) with minimally involved reagents, only by controlling the original morphological stability of SP through pH adjustment of the synthesis media. SP thiolation increased the localization of AuNPs selectively on the cell wall without using a reducing agent (Au-TSP). SP autofluorescence, along with the high X-ray absorption of AuNPs, was employed for dual-modal fluorescence and computed tomography (FL/CT) imaging. Furthermore, the theranostic efficacy of Au-SP was improved through a targeting process with folic acid (Au-SP@CF). High tumor inhibition effects were obtained by the excellent photothermal performance of Au-SP@CF in both in vitro and in vivo analyses. Of particular note, a comparison of the photothermal effect of Au-SP@CF with the naked SP and calcined form of Au-SP@CF not only indicated the key role of the helical architecture of AuNPs in achieving a high photothermal effect but also led to the formation of new gold microspiral biohybrids (Au-MS) over the calcination process. In short, well-controllable immobilization of AuNPs, appropriate biodegradability, good hemocompatibility, long-term biosafety, accurate imaging, high tumor suppression, and low tumor metastasis effects under laser irradiation are an array of intriguing attributes, making the proposed biohybrid a promising theranostic system for FL/CT-imaging-guided PTT.

Exploring the cancer-testis antigen BORIS to design a novel multi-epitope vaccine against breast cancer based on immunoinformatics approaches.

Recently, cancer immunotherapy has gained lots of attention to replace the current chemoradiation approaches and multi-epitope cancer vaccines are manifesting as the next generation of cancer immunotherapy. Therefore, in this study, we used multiple immunoinformatics approaches along with other computational approaches to design a novel multi-epitope vaccine against breast cancer. The most immunogenic regions of the BORIS cancer-testis antigen were selected according to the binding affinity to MHC-I and II molecules as well as containing multiple cytotoxic T lymphocyte (CTL) epitopes by multiple immunoinformatics servers. The selected regions were linked together by GPGPG linker. Also, a T helper epitope (PADRE) and the TLR-4/MD-2 agonist (L7/L12 ribosomal protein from mycobacterium) were incorporated by A(EAAAK)3A linker to form the final vaccine construct. Then, its physicochemical properties, cleavage sites, TAP transport efficiency, B cell epitopes, IFN-γ inducing epitopes and population coverage were predicted. The final vaccine construct was reverse translated, codon-optimized and inserted into pcDNA3.1 to form the DNA vaccine. The final vaccine construct was a stable, immunogenic and non-allergenic protein that contained numerous CTL epitopes, IFN-γ inducing epitopes and several linear and conformational B cell epitopes. Also, the final vaccine construct formed stable and significant interactions with TLR-4/MD-2 complex according to molecular docking and dynamics simulations. Moreover, its world population coverage for HLA-I and HLA-II were about 93% and 96%, respectively. Taking together, these preliminary results can be used as an appropriate platform for further experimental investigations. Communicated by Ramaswamy H. Sarma.

Diagnostic and prognostic value of stem cell factor plasma level in glioblastoma multiforme patients.

BACKGROUND: Investigation of novel blood-circulating agents as potential biomarkers for glioblastoma multiforme (GBM) patients' diagnosis and monitoring has gained lots of attention, due to limitations of imaging modalities and invasive tissue biopsy procedures. The present study aims to assess the diagnostic and prognostic values of preoperative stem cell factor (SCF) plasma level in GBM patients. METHODS: Preoperative plasma samples from 58 GBM patients and 20 patients with nonglial tumors and 30 healthy controls were obtained. SCF levels were measured by employing the enzyme-linked immunosorbent assay test and the values were compared between these three groups. Then, the association of SCF plasma level and tumor volume, progression-free survival (PFS), and overall survival (OS) for the GBM patients were evaluated. RESULTS: Mean preoperative SCF plasma level of the GBM patients (2.80 ± 1.52 ng/ml) was significantly higher (p < 0.0001) than the healthy controls (0.80 ± 0.24 ng/ml) and patients with nonglial tumor (1.41 ± 0.76 ng/ml). Receiver operating characteristic analysis revealed that the preoperative SCF plasma level could distinguish the GBM patients from healthy controls and patients with nonglial tumors with the area under curve values of 0.915 and 0.790, respectively. However, no significant association was observed between the GBM patients' preoperative SCF plasma levels and tumors' volume (Spearman Rho correlation coefficient, 0.1847; 95% CI, p = 0.1652). The GBM patients were divided into two subgroups based on mean preoperative SCF plasma levels (2.80 ng/ml). No significant difference was observed between the patients' PFS (p = 0.3792) and OS (p = 0.1469) at these two subgroups. CONCLUSION: Taking together, the SCF plasma level can serve as a novel diagnostic blood-circulating biomarker for patients with GBM. However, its plasma level is not correlated with GBM patients' tumor volume, PFS, or OS.