Transplantation of human umbilical cord mesenchymal stem cells optimized with IFN-γ is a potential procedure for modification of motor impairment in multiple sclerosis cases: a preclinical systematic review and meta-analysis study.

Stem cells transplantation (SCT) is known as a newfound strategy for multiple sclerosis (MS) treatment. Human umbilical cord mesenchymal stem cells (hUCMSCs) contain various regenerative features. Experimental autoimmune encephalomyelitis (EAE) is a laboratory model of MS. This meta-analysis study was conducted to assess the overall therapeutic effects of hUCMSCs on reduction of clinical score (CS) and restoration of active movement in EAE-induced animals. For comprehensive searching (in various English and Persian databases until May 1, 2024), the main keywords of "Experimental Autoimmune Encephalomyelitis", "Multiple Sclerosis", "Human", "Umbilical Cord", "Mesenchymal", and "Stem Cell" were hired. Collected data were transferred to the citation manager software (EndNote x8) and duplicate papers were merged. Primary and secondary screenings were applied (according to the inclusion and exclusion criteria) and eligible studies were prepared for data collection. CS of two phases of peak and recovery of EAE were extracted as the difference in means and various analyses including heterogeneity, publication bias, funnel plot, and sensitivity index were reported. Meta-analysis was applied by CMA software (v.2), P<0.05 was considered a significant level, and the confidence interval (CI) was determined 95% (95% CI). Six eligible high-quality (approved by ARRIVE checklist) papers were gathered. The difference in means of peak and recovery phases were -0.775 (-1.325 to -0.225; P=0.006; I2=90.417%) and -1.230 (-1.759 to -0.700; P<0.001; I2=93.402%), respectively. The overall therapeutic effects of SCT of hUCMSCs on the EAE cases was -1.011 (95% CI=-1.392 to -0.629; P=0.001). hUCMSCs transplantation through the intravenous route to the animal MS model (EAE) seems a considerably effective procedure for the alleviation of motor defects in both phases of peak and recovery.

Neuroprotective activity of green synthesized silver nanoparticles against methamphetamine-induced cell death in human neuroblastoma SH-SY5Y cells.

The present study aimed to investigate the neuroprotective activity of the black peel pomegranate extract, and silver nanoparticles (AgNPs) biosynthesized using the extract. We pretreated the human neuroblastoma SH-SY5 cells with the extract and AgNPs and evaluated the neuroprotective activity of these agents against methamphetamine (Meth) cytotoxicity. The NPs were spherical with 19 ± 8 nm size, - 28 mV surface charge, and 0.20 PDI. Meth killed the cells by increasing proapoptotic (Bax, PTEN, AKT, PI3K, NF-κB, P53, TNF-α, Cyt C, and Cas 3) and decreasing the antiapoptotic genes (Bcl-2) expression. Exposure to Meth caused DNA fragmentation and increased the intercellular ROS and malondialdehyde (MDA) levels while reducing the mitochondrial membrane potential (MMP). A 4-h pretreatment of the cells with the extract and AgNPs could retain the viability of the cells above 80% by increasing the Bcl-2 expression up to fourfold and inhibiting the cell death pathways. ROS, MDA, and MMP levels in the pretreated cells were close to the control group. The percentage of necrosis in cells pretreated with the extract and AgNPs declined to 32% and 8%, respectively. Our promising findings indicated that AgNPs could reduce Meth-induced oxidative stress and prevent necrotic and apoptotic cell death by regulating related genes' expression.

A Short Cationic Peptide Derived from Cecropin and Melittin Peptides Induce Apoptosis in Jurkat and Raji Leukemia Cell Lines.

BACKGROUND: The creation of brand-new, potent, and less harmful medications to treat leukemia is urgently needed. Antimicrobial peptides (AMPs) have drawn a lot of interest as potential substitutes for chemotherapy. OBJECTIVE: In the present investigation, the anticancer activity of CM11, a short cationic AMP, was assessed on Jurkat and Raji leukemia cell lines and peripheral blood mononuclear cells (PBMCs). METHODS: Different CM11 doses were applied to the Jurkat and Raji cell lines and PBMCs throughout a 24-hour period. The impact of the CM11 on cell viability and toxicity was assessed using an MTT assay. Flow cytometry and Real-Time PCR were used to analyze the effect of this peptide on apoptotic/necrosis pathways and assess the ratio expression of the P53 and Bcl-2 genes, respectively. RESULTS: Despite the fact that peptide toxicity was successful in a variety of cell lines, cancer cells were more sensitive to the medication. The survival of Jurkat and Raji cell lines treated with 32 µg/ml peptide was 47% and 51%, respectively, while the survival of normal PBMC cells was about 65%. According to flow cytometry, Jurkat and Raji cells exposed to peptide had much greater levels of apoptosis than PBMCs. Peptide-treated cells were associated with increased expression of P53 the gene and decreased expression of the Bcl-2 gene. CONCLUSION: These results revealed that the CM11 caused more cytotoxicity to leukemia Raji and Jurkat leukemia cells compared to the normal cells by apoptosis pathway. Our findings demonstrated the potential of CM11 peptide to develop as a new antileukemic agent.

Evaluation of antimicrobial and cytotoxic effects of Echinacea and Arctium extracts and Zataria essential oil.

Dental caries and oral infections have become a widespread issue in the modern world. This study aimed to investigate the antibacterial, antifungal, and cytotoxicity characteristics of the extracts of Echinacea purpura, Arctium lappa, and the essential oil of Zataria multiflora as a potential herbal mouthwash. The essential oil of Z. multiflora leaves and the extracts of E. purpurea and A. lappa roots were prepared. The characterization was carried out by GC-MS and also, total phenol and flavonoid were assed for all three samples. The antimicrobial and anti-biofilm effects were evaluated against Streptococcus mutans, Streptococcus mitis, Streptococcus salivarius, Lactobacillus acidophilus, Escherichia coli, Staphylococcus aureus, and Candida albicans. The cytotoxic effect of the samples was evaluated on HEK 293 and HDFa cells by MTT test. Thymol and carvacrol contents in EO of Z. multiflora were measured at 31% and 42.2%, respectively. A. lappa had the lowest total phenolic and flavonoid value among the samples. On the other hand, the total phenolic content of Z. multiflora and the total flavonoid content of E. purpurea were the highest. The MIC values of Zataria, Arctium, and Echinacea against S. mutans were 0.011% v/v, 187.5 mg/ml, and 93.75 mg/ml, while MBC were 0.011% v/v, 375 mg/ml, and 187.5 mg/ml, respectively. The formulation showed bactericidal activity against S. mutans in the concentration of 5.86 mg/ml for Echinacea and Burdock extracts and 0.08 µl/ml for EO of Zataria. The formulation significantly affected microbial biofilm formation and induced biofilm degradation. The cell viability percentages were higher than 50% during 24 and 48 h. The formulation had a significant antimicrobial effect on cariogenic bacteria and C. albicans, with the lowest cytotoxic effects. Therefore, this formulation can be an appropriate candidate for mouthwash.

Emerging tissue engineering strategies for the corneal regeneration.

Cornea as the outermost layer of the eye is at risk of various genetic and environmental diseases that can damage the cornea and impair vision. Corneal transplantation is among the most applicable surgical procedures for repairing the defected tissue. However, the scarcity of healthy tissue donations as well as transplantation failure has remained as the biggest challenges in confront of corneal grafting. Therefore, alternative approaches based on stem-cell transplantation and classic regenerative medicine have been developed for corneal regeneration. In this review, the application and limitation of the recently-used advanced approaches for regeneration of cornea are discussed. Additionally, other emerging powerful techniques such as 5D printing as a new branch of scaffold-based technologies for construction of tissues other than the cornea are highlighted and suggested as alternatives for corneal reconstruction. The introduced novel techniques may have great potential for clinical applications in corneal repair including disease modeling, 3D pattern scheming, and personalized medicine.

Lipid-based Nanoparticles for the Targeted Delivery of Anticancer Drugs: A Review.

Cancer is one of the leading causes of mortality worldwide. Although chemotherapeutic agents have been effectively designed to increase the survival rates of some patients, the designed chemotherapeutic agents necessarily deliver toxic chemotherapeutic drugs to healthy tissues, resulting in serious side effects. Cancer cells can often acquire drug resistance after repeatedly administering current chemotherapeutic agents, restricting their efficacy. Given such obstacles, investigators have attempted to distribute chemotherapeutic agents using targeted drug delivery systems (DDSs), especially nanotechnology-based DDSs. The lipid-based nanoparticles (LBNPs) are a large and complex class of substances utilized to manage various diseases, especially cancers. Liposomes seem to be the most frequently employed LBNPs, owing to their high biocompatibility, bioactivity, stability, and flexibility. Solid lipid NPs and non-structured lipid carriers have lately received a lot of interest. In addition, several reports focused on novel therapies via LBNPs to manage various forms of cancer. In the present research, the latest improvements in applying LBNPs have been shown to deliver different therapeutic agents to cancerous cells and be a quite successful candidate in cancer therapy.

Polymeric nanoparticles as carrier for targeted and controlled delivery of anticancer agents.

In recent decades, many novel methods by using nanoparticles (NPs) have been investigated for diagnosis, drug delivery and treatment of cancer. Accordingly, the potential of NPs as carriers is very significant for the delivery of anticancer drugs, because cancer treatment with NPs has led to the improvement of some of the drug delivery limitations such as low blood circulation time and bioavailability, lack of water solubility, drug adverse effect. In addition, the NPs protect drugs against enzymatic degradation and can lead to the targeted and/or controlled release of the drug. The present review focuses on the potential of NPs that can help the targeted and/or controlled delivery of anticancer agents for cancer therapy.

CdS nanocrystals/graphene oxide-AuNPs based electrochemiluminescence immunosensor in sensitive quantification of a cancer biomarker: p53.

An ultrahigh sensitive, simple and reliable Electrochemiluminescence (ECL) immunosensor for selective quantification of p53 protein was designed according to the enhancement effects of AuNPs on ECL emission of CdS nanocrystals (CdS NCs). CdS NCs were immobilized on the glassy carbon electrode and AuNPs introduced to the process through formation of a sandwich-type immunocomplex between first anti-p53/p53/ secondary anti-p53. ECL of CdS NCs firstly evoked the SPR of AuNPs which in return amplified the CdS NCs ECL intensity. By using graphene oxide in immunosensor fabrication procedure, and attaching more AuNPs on the surface of the electrode, the ECL intensity was further increased resulting in much higher sensitivity. After applying the optimum conditions, the linear range of the developed immunosensor was found between 20 and 1000 fg/ml with a calculated limit of detection of 4 fg/ml. Moreover, the interference, reproducibility and storage stability studies of the immunosensor were investigated. Finally, immunosensor's authenticity was evaluated by detecting the p53 protein in human spikes which offers it as a potential in early detection of cancer, monitoring the cancer progress and clinical prognosis.

Stem cell therapy for lung diseases: From fundamental aspects to clinical applications.

The respiratory system is a complex group of organs in the human body, all of which are necessary in breathing. Due to its special anatomy and composition, after exposure to various damaging factors such as micro particles, carbon granules and toxic gases, the respiratory system can be affected by a variety of damage without return to its original state. Currently, the prevalence of lung diseases, including asthma, and chronic obstructive pulmonary diseases, such as emphysema, has increased remarkably. New therapeutic approaches are desperately needed to discover regenerative medicine approaches, especially cell therapy. This review summarizes the recent advances in stem cell treatments and the research efforts conducted through the application of stem cell therapy for respiratory system diseases. In particular, researchers have used animal models to gather data about treating lung injury by stem cell transplantation. This review concentrated on the findings about route, timing and adjustment of cell transplantation dose, optimum stem cell type selection and potency marker of cells as therapeutic agents. These factors are essential subjects for approval and clinical transplantation. The current clinical trials aiming at treatment of lung diseases by stem cells are mentioned and discussed.

Identification and characterization of a cathepsin L-like cysteine protease from Rhipicephalus (Boophilus) annulatus.

The tick Rhipicephalus (Boophilus) annulatus is one of the most important ectoparasites of bovines and is responsible for the transmission of different pathogens such as Babesia and Anaplasma. Cysteine proteases are involved in several host-tick interactions including invasion of host tissues, immune evasion, pathogen transmission, embryogenesis and blood digestion. In this study, the gene encoding R. annulatus cathepsin L-like enzyme (RaCL1) was cloned into pTZ57R/T vector, sequenced and analyzed using bioinformatics approaches. The nucleotide length of RaCL1 was 999 bp. Bioinformatics analysis showed 332 amino acids with an approximate molecular weight of 36.3 kDa which contained a signal peptide sequence (18 amino acids), pro-region (97 amino acids) and mature enzyme (217 amino acids). Multiple sequence alignment of the RaCL1 revealed high similarity to cathepsin L-like cysteine proteases from other tick species such as Rhipicephalus (Boophilus) microplus and Amblyomma variegatum. Based on bioinformatics analyses, results of this work suggest that RaCL1 can be a suitable candidate for the development of vaccine against R. annulatus.

Investigation of the antibacterial activity of a short cationic peptide against multidrug-resistant Klebsiella pneumoniae and Salmonella typhimurium strains and its cytotoxicity on eukaryotic cells.

With the growing microbial resistance to conventional antimicrobial agents, the development of novel and alternative therapeutic strategies are vital. During recent years novel peptide antibiotics with broad spectrum activity against many Gram-positive and Gram-negative bacteria have been developed. In this study, antibacterial activity of CM11 peptide (WKLFKKILKVL-NH2), a short cecropin-melittin hybrid peptide, is evaluated against antibiotic-resistant strains of Klebsiella pneumoniae and Salmonella typhimurium as two important pathogenic bacteria. To appraise the antibacterial activity, minimal inhibitory concentration (MIC), minimal bactericidal concentration (MBC) and bactericidal killing assay were utilized with different concentrations (2-128 mg/L) of peptide. To evaluate cytotoxic effect of peptide, viability of RAJI, Hela, SP2/0, CHO, LNCAP cell lines and primary murine macrophage cells were also investigated with MTT assay in different concentrations (3-24 and 0.5-16 mg/L, respectively). MICs of K. pneumoniae and S. typhimurium isolates were in range of 8-16 and 4-16 mg/L, respectively. In bactericidal killing assay no colonies were observed at 2X MIC for K. pneumoniae and S. typhimurium isolates after 80-90 min, respectively. Despite the fact that CM11 reveals no significant cytotoxicity on RAJI, Hela, SP2/0, and CHO cell lines beneath 6 mg/L at first 24 and 48 h, the viability of LNCAP cells are about 50 % at 3 mg/L, which indicates strong cytotoxicity of the peptide. In addition, macrophage toxicity by MTT assay showed that LD50 of CM11 peptide is 12 µM (16 mg/L) after 48 h while in this concentration after 24 h macrophage viability was about 70 %.