The Effects of Mesenchymal Stem Cells Loaded with Oncolytic Coxsackievirus A21 on Mouse Models of Colorectal Cancer.

BACKGROUND: Cancer is a major cause of death worldwide. Colorectal cancer is the second most common type. Additional treatments like chemotherapy and radiation therapy may be recommended. Developing new techniques is vital due to drug resistance and a lack of targeted therapies. OBJECTIVE: In this study, the effects of mesenchymal stem cells (MSCs) loaded with oncolytic Coxsackievirus A21 (CVA21) on a mouse model of CRC were investigated. METHODS: The therapeutic potency of MSCs loaded with oncolytic CVA21 was evaluated in an experimental mouse model of colorectal cancer which received an injection CT26 cells per mouse subcutaneously. Splenocyte proliferation index, lactate dehydrogenase (LDH) assay, nitric oxide (NO) production assessment, and cytokine assay (IFN-γ, IL-4, IL-10, and TGF-ß) in the splenocyte supernatant were all used to evaluate the impact of MSCs loaded with CVA21. RESULTS: The results of this study showed that the treatment of a mouse model of colorectal cancer with MSCs loaded with oncolytic CVA21 could significantly suppress the tumor growth, which was accompanied by stimulation of splenocytes proliferation index, an increase of NO and LDH. Also, MSCs loaded with oncolytic CVA21 increased the secretion of IFN-γ and decreased the secretion of IL-4, IL-10, and TGF-ß. CONCLUSION: The results of the current study suggest that MSCs loaded with oncolytic CVA21 therapy for the CRC mouse model may have some potential advantages. On the other hand, the results of the study showed that, in addition to activating the acquired immune system, the use of MSCs loaded with oncolytic CVA21 also stimulates the innate immune system by increasing levels of nitric oxide.

Investigating the potential of oncolytic viruses for cancer treatment via MSC delivery.

Mesenchymal stem cells (MSCs) have attracted considerable interest as a promising approach for cancer treatment due to their ability to undergo tumor-trophic migration. MSCs possess the unique ability to selectively migrate to tumors, making them an excellent candidate for targeted delivery of oncolytic viruses (OVs) to treat isolated tumors and metastatic malignancies. OVs have attracted attention as a potential treatment for cancer due to their ability to selectively infect and destroy tumor cells while sparing normal cells. In addition, OVs can induce immunogenic cell death and contain curative transgenes in their genome, making them an attractive candidate for cancer treatment in combination with immunotherapies. In combination with MSCs, OVs can modulate the tumor microenvironment and trigger anti-tumor immune responses, making MSC-releasing OVs a promising approach for cancer treatment. This study reviews researches on the use of MSC-released OVs as a novel method for treating cancer. Video Abstract.

New role of bacteriophages in medical oncology.

Targeted treatment of cancer is one of the most paramount approaches in cancer treatment. Despite significant advances in cancer diagnosis and treatment methods, there are still significant limitations and disadvantages in the field, including high costs, toxicity, and unwanted damage to healthy cells. The phage display technique is an innovative method for designing carriers containing exogenic peptides with cancer diagnostic and therapeutic properties. Bacteriophages possess unique properties making them effective in cancer treatment. These characteristics include the small size enabling them to penetrate vessels; having no pathogenicity to mammals; easy manipulation of their genetic information and surface proteins to introduce vaccines and drugs to cancer tissues; lower cost of large-scale production; and greater stimulation of the immune system. Bacteriophages will certainly play a more effective role in the future of medical oncology; however, studies are in the early stages of conception and require more extensive research. We aimed in this review to provide some related examples and bring insights into the potential of phages as targeted vectors for use in cancer diagnosis and treatment, especially regarding their capability in gene and drug delivery to cancer target cells, determination of tumor markers, and vaccine design to stimulate anticancer immunity.

Biochemical, Serological and Immunological Tests for Diagnosis of Coronavirus Disease 2019 (COVID-19) Patients: A Comprehensive Systematic Review and Meta-analysis.

BACKGROUND: Recent studies have suggested the role of primary laboratory tests in addition to clinical symptoms for patients suspected to have coronavirus disease 2019 (COVID-19), which play a significant role in the diagnosis of COVID-19. However, the results of these studies are contradictory. The present study was conducted to evaluate biochemical, serological, and immunological tests for the diagnosis of COVID-19 patients. METHODS: This study was presented in accordance with the PRISMA protocol. This protocol is registered with the code CRD42019145410 in PROSPERO. We conducted a comprehensive literature search in databases, including Web of Science, PubMed/Medline, CINAHL Scopus, Cochrane Library, EMBASE, Science Direct, and EBSCO to find citations from the beginning of January 2019 until the beginning of April 2020 without any restrictions. RESULTS: Finally, 51 studies, including 5,490 COVID-19 patients, were included in the present metaanalysis. The prevalence of different factors observed in laboratory findings was as follows: the prevalence of lymphopenia in patients with COVID-19 accounted for 51.6% (95% CI: 44.0-59.1), elevated C-reactive protein (CRP) was 63.6% (95% CI: 57.0-69.8), elevated erythrocyte sedimentation rate (ESR) was 62.5% (95% CI: 50.1-73.5), elevated tumor necrosis factor alpha (TNFα) was 28.7% (95% CI: 9.0-62.1), elevated serum amyloid-A level was 74.7% (95% CI: 50.0-89.7), elevated procalcitonin level was 72.6% (95% CI: 58.1-83.5), elevated interleukin-6 level was 59.9% (95% CI: 48.2-70.5), reduced CD3 level was 68.3% (95% CI: 50.1-82.2), reduced CD4 level was 62.0% (95% CI: 51.1- 71.6), elevated lactate dehydrogenase (LDH) level accounted for 53.1% (95% CI: 43.6-62.4), elevated brain natriuretic peptide (BNP) accounted for 48.9% (95% CI: 30.4-67.7), reduced albumin and reduced pre-albumin levels in patients with COVID-19 were estimated to be 54.7% (95% CI: 38.1-70.2) and 49.0% (95% CI: 26.6-71.8), and D-dimer level was 44.9% (95% CI: 31.0-59.6). CONCLUSION: The results show lymphopenia, elevated ESR level, elevated CRP level, elevated serum amyloid-A, elevated TNFα, elevated procalcitonin level, elevated interleukin-6 level, reduced CD3, reduced CD4, elevated BNP, elevated LDH, reduced albumin, reduced pre-albumin, and elevated Ddimer levels as the most common findings at the time of admission.

Anti-metastatic effect of taraxasterol on prostate cancer cell lines.

Background and purpose: Prostate cancer is the second cause of death among men. Nowadays, treating various cancers with medicinal plants is more common than other therapeutic agents due to their minor side effects. This study aimed to evaluate the effect of taraxasterol on the prostate cancer cell line. Experimental approach: The prostate cancer cell line (PC3) was cultured in a nutrient medium. MTT method and trypan blue staining were used to evaluate the viability of cells in the presence of different concentrations of taraxasterol, and IC50 was calculated. Real-time PCR was used to measure the expression of MMP-9, MMP-2, uPA, uPAR, TIMP-2, and TIMP-1 genes. Gelatin zymography was used to determine MMP-9 and MMP-2 enzyme activity levels. Finally, the effect of taraxasterol on cell invasion, migration, and adhesion was investigated. Findings/Results: Taraxasterol decreased the survival rate of PC3 cells at IC50 time-dependently (24, 48, and 72 h). Taraxasterol reduced the percentage of PC3 cell adhesion, invasion, and migration by 74, 56, and 76 percent, respectively. Real-time PCR results revealed that uPA, uPAR, MMP-9, and MMP-2 gene expressions decreased in the taraxasterol-treated groups, but TIMP-2 and TIMP-1 gene expressions increased significantly. Also, a significant decrease in the level of MMP-9 and MMP-2 enzymes was observed in the PC3 cell line treated with taraxasterol. Conclusion and implications: The present study confirmed the therapeutic role of taraxasterol in preventing prostate cancer cell metastasis in the in-vitro study.

Cytokine profile and antioxidants status in the moderate and severe COVID-19 patients: a trial of ozone therapy impact as a medicinal supplement.

BACKGROUND: Complementary ozone therapy has been identified as a revolutionary medical technique for a number of goals and ailments. At the present, it has been shown that ozone has medicinal qualities, such as antibacterial, antifungal, and antiparasitic properties. Coronavirus (SARS-CoV-2) is quickly spread over the globe. Cytokine storms and oxidative stress seem to play a substantial role in the most of acute attacks of the disease. The aim of this research was to assess the therapeutic advantages of complementary ozone therapy on the cytokine profile and antioxidant status in COVID-19 patients. METHODS: The statistical sample of this study included two hundred patients with COVID-19. One hundred COVID-19 patients (treatment group) received 240 ml of the patient's blood and an equal volume of O2/O3 gas at a concentration of 35-50 µg/ml daily, which gradually increased in concentration, and were kept for 5-10 days and one hundred patients (control group) received standard treatment. The secretion levels of IL-6, TNF-α, IL-1ß, IL-10 cytokines, SOD, CAT and GPx were compared between control patients (standard treatment) and standard treatment plus intervention (ozone) before and after treatment. RESULTS: The findings indicated a significant decrease in the level of IL-6, TNF-α, IL-1ß in group receiving complementary ozone therapy in compared with control group. Furthermore, a significant increase was found in the level of IL-10 cytokine. Moreover, SOD, CAT and GPx levels revealed a significant increase in complementary ozone therapy group compared to control group. CONCLUSIONS: Our results revealed that complementary ozone therapy can be used as a medicinal complementary therapy to reduce and control inflammatory cytokines and oxidative stress status in patients with COVID-19 as revealed its antioxidant and anti-inflammatory effects.

Efficacy of ozone therapy on visual evoked potentials in diabetic patients.

BACKGROUND: The involvement of the central nervous system is a frequent yet underestimated complication of diabetes mellitus. Visual evoked potentials (VEP) are a simple, sensitive, and noninvasive method for detecting early alterations in central optic pathways. The objective of this paralleled randomized controlled trial was to evaluate the impact of ozone therapy on visual pathways in diabetic patients. METHODS: Sixty patients with type 2 diabetes visiting clinics of Baqiyatallah university in Tehran (Iran) hospital were randomly assigned to two experimental groups: Group 1 (N = 30) undergoing a cycle of 20 sessions of systemic oxygen-ozone therapy in addition to standard therapy for metabolic control; Group 2 (N = 30)-serving as control-receiving only standard therapy against diabetes. The primary study endpoints were two VEP parameters; P100 wave latency and P100 amplitude at 3 months. Moreover, HbA1c levels were measured before the start of treatment and three months later as secondary study endpoint. RESULTS: All 60 patients completed the clinical trial. P100 latency significantly reduced at 3 months since baseline. No correlation was found between repeated measures of P100 wave latency and HbA1c (Pearson's r = 0.169, p = 0.291). There was no significant difference between baseline values and repeated measures of P100 wave amplitude over time in either group. No adverse effects were recorded. CONCLUSIONS: Ozone therapy improved the conduction of impulses in optic pathways of diabetic patients. The improved glycemic control following ozone therpay may not fully explain the reduction of P100 wave latency though; other mechanistic effects of ozone may be involved.

Human Hematopoietic Stem Cells Co-cultured in 3D with Stromal Support to Optimize Lentiviral Vector-mediated Gene Transduction.

HSC transplantation (HSCT) has emerged as a promising treatment option for hematological and immunological disorders. Unfortunately, many viral vectors are inefficient at transduction, limiting the number of cells available for gene therapy in cord blood HSC transplantation. Combining ex vivo expansion and genetic manipulation of cord blood cells is a potential gene therapy approach. We present a 3D co-culture method using a demineralized bone matrix scaffold to optimize lentiviral vector-mediated gene transduction. pLenti-III-miR-GFP-has-miR-124 was transduced into cord blood HSCs. Transduced CD34 + cells co-cultured on the stromal layer for 72 h under cytokine-free conditions. We performed flow cytometry, colony assays, real-time polymerase chain reaction, and SEM morphological analysis. Seventy-two hours after transduction, when pLentiIII-miR-GFP-has-miR-124 and control vector-transduced expanded cord blood HSCs were compared to non-transduced expanded cord blood HSCs, the findings revealed 15 ± 3.04 and 55 ± 3.05-fold increases in miR-124 mRNA expression, respectively. Compared to a control culture on the same day, the expansion of CD34+, CD38-HSCs in 3D culture increased 544 ± 31.09 fold. This result demonstrated that the 3D-culture system could emerge as a novel approach to overcoming the current limitations of cord blood HSC transduction. In the future, this research could be applied in a therapeutic setting.

Cell therapy procedure using anti-inflammatory macrophage M2 can potentially reduce Clinical Score in animals with Experimental Autoimmune Encephalomyelitis: A preclinical systematic review and meta-analysis study.

Macrophage M2 (MP2)-based cell therapy is a novel medicinal treatment for animals with Experimental Autoimmune Encephalomyelitis (EAE) as an experimental model of multiple sclerosis (MS). This systematic review and meta-analysis study was designed to assess the overall therapeutic effects of MP2 cell therapy on Clinical Score and motor impairment in EAE-induced animals. All experiments on MP2 cell therapy in animals with EAE were gathered (by October 2, 2022) from English (PubMed, Scopus, WoS, Science Direct, and ISC) and Persian (MagIran and SID) databases. The searching strategy was designed using "Experimental Autoimmune Encephalomyelitis," "Multiple Sclerosis," and "Macrophage M2" keywords. Following primary and secondary screenings, eligible papers were selected based on the PRISMA 2020 guideline, and the study quality was assessed using the Animal Research: Reporting of In Vivo Experiments (ARRIVE) checklist. The difference in means of Clinical Score (score 0-5) as the effect size (ES) was analyzed based on the random effect model (CMA software, v.2). Subgrouping (EAE phases of Onset, Peak, and Recovery) was applied, and I2 index was used to assess the heterogeneity index. Publication bias and sensitivity indices were also evaluated. P < 0.05 was considered significant, and the confidence interval (CI) was determined 95%. Among 22 gathered papers, medium to high quality studies were selected for meta-analysis. Difference in means, P value, and I2 for Onset, Peak, and Recovery phases were 0.082 (CI95%: -0.323-0.159, P value: 0.504, I2 : 67.961%), -0.606 (CI95%: -1.518 to -0.305, P value: 0.192, I2 : 96.070%), and -1.103 (CI95%: -1.390 to -0.816, P value: 0.000, I2 : 30.880%), respectively and Overall Effect was found -0.509 (CI95%: -0.689 to -0.328, P value < 0.001). Also, P value (two-tailed) indices for publication bias were 0.366 and 0.583 for Egger's regression intercept and Begg rank correlation, respectively. The P value for sensitivity was detected 0.003. Cell therapy procedure using MP2 can potentially alleviate the Clinical Scores Index and correct the motor defects in Recovery phase of EAE animals. In healthy mice, the brain and myelin surrounding neurons are in a healthy and physiological state (1). To evaluate MS in humans, it is necessary to model this type of disease in animals using EAE procedure through subcutaneous injection of CFA, MOG35-55 , MT, and Pert. Thus, inflammation and autoimmunity occur, which finally lead to myelin destruction and motor symptoms (2). By aspiration of progenitor cells available in bone marrow, the MP2 can be isolated and cultured. By activation of these types of cells, a rich collection of MP2 can be prepared for the cell-therapy process (3). After injection through the tail vein or intra-peritoneal procedure, these cells can be located in CNS through crossing from the BBB. They begin their anti-inflammatory activities and help repair the damaged myelin (4). Eventually, the clinical symptoms can be modified considerably, and the animal motor function improves (5). CFA, complete Freund's adjuvant; MOG35-55 , myelin oligodendrocyte glycoprotein; MT, Mycobacterium tuberculosis; Pert, pertussis; EAE, Experimental Autoimmune Encephalomyelitis; BM, bone marrow; MP2, macrophage M2; and BBB, blood brain barrier.

Advances in early diagnosis of cervical cancer based on biosensors.

Human papillomavirus (HPV) is a causative agent of cervical cancer among women worldwide. Serological and molecular tests are commonly used to detect and identify HPV, but all the detection methods for HPV have some limitations. Nowadays, considerable advancements in nanosensors have enabled monitoring of hybridization procedures dynamically for HPV detection. Biosensors, as effective, quick, economical, and highly sensitive tools, can be used in the diagnosis of HPV as an alternative technique instead of other detection methods. Biosensor detection methods of HPV in use from 2000 to 2021 were investigated using several databases such as Google Scholar, Scopus, PubMed, and the Scientific Information Database. Furthermore, a manual search of the references of the retrieved articles was performed. On analyzing the most recently developed biosensors for HPV identification, we observed that three biosensor systems, electrochemical, optical, and piezoelectric systems, are the main transducers used in the development of HPV biosensors. The aim of this review is to examine recent research on biosensors for the detection of HPV and perform a comparison with other diagnostic methods. Considering the importance of rapid HPV detection in the control of infection and development of public health measures, improvement of biosensors as an economical and quick method can be very useful in the diagnosis of HPV.

Therapeutic potential of CAR T cell in malignancies: A scoping review.

Although tremendous advancements in cancer therapy over the last several years, cancer still is a complex illness to cure. Traditional cancer treatments, including chemotherapy, radiotherapy, and surgery, have a poor therapeutic effect, emphasizing the significance of employing innovative treatments like activated cell therapy. Chimeric antigen receptor T cell is one of the most prevalent types of activated cell therapy have been developed to direct T lymphocytes toward cancers (CAR-T cells). CAR-T cells therapy has illustrated poor impact versus solid tumors despite the remarkable success in patients suffering from hematological malignancies. CAR-T cells must overcome various hurdles to obtain full responses to solid tumors, including growth, stability, trafficking, and destiny inside tumors. As a result, novel treatment methods will entail overcoming the challenges that CAR-T cells face in solid tumors. The use of CAR-T cells in combination with other therapeutic approaches such as chemotherapy, radiotherapy, immuno-checkpoint inhibitors, and oncolytic viruses can promote the effectiveness of CAR-T cell therapy for the treatment of solid tumors. However, more research is needed to determine the safety and effectiveness of these therapies. CAR-T cell treatment success rates vary by type of disease, but are predicted to reach up to 90% in patients with leukemia. However, since this kind of immunotherapy is still in its infancy, there is much to learn about its efficacy. This review provided an in-depth examination of CAR-T cell therapy and its success and failure as a cancer treatment approach. We also discuss combination therapies with CAR-T Cell.

Efficacy of a Low Dose of Melatonin as an Adjunctive Therapy in Hospitalized Patients with COVID-19: A Randomized, Double-blind Clinical Trial.

BACKGROUND: Melatonin has been known as an anti-inflammatory agent and immune modulator that may address progressive pathophysiology of coronavirus disease 2019 (COVID-19). AIM OF THE STUDY: To evaluate the clinical efficacy of adjuvant, use of melatonin in patients with COVID-19. METHODS: This single-center, double-blind, randomized clinical trial included 74 hospitalized patients with confirmed mild to moderate COVID-19 at Baqiyatallah Hospital in Tehran, Iran, from April 25, 2020-June 5, 2020. Patients were randomly assigned in a 1:1 ratio to receive standard of care and standard of care plus melatonin at a dose of 3 mg three times daily for 14 d. Clinical characteristics, laboratory, and radiological findings were assessed and compared between two study groups at baseline and post-intervention. Safety and clinical outcomes were followed up for four weeks. RESULTS: A total of 24 patients in the intervention group and 20 patients in the control group completed the treatment. Compared with the control group, the clinical symptoms such as cough, dyspnea, and fatigue, as well as the level of CRP and the pulmonary involvement in the intervention group had significantly improved (p <0.05). The mean time of hospital discharge of patients and return to baseline health was significantly shorter in the intervention group compared to the control group (p <0.05). No deaths and adverse events were observed in both groups. CONCLUSIONS: Adjuvant use of melatonin has a potential to improve clinical symptoms of COVID-19 patients and contribute to a faster return of patients to baseline health.

Comparison of oncolytic virotherapy and nanotherapy as two new miRNA delivery approaches in lung cancer.

Lung cancer is known as the second leading cause of cancer death. Finding ways to detect early-stage lung cancer can remarkably increase the survival rate. Biomarkers such as microRNAs can be helpful in cancer diagnosis, predicting its prognosis, and patients' chances of survival. Numerous studies have confirmed the correlation between microRNA expression and the likelihood of patients surviving after treatment. Consequently, it is necessary to study the expression profile of microRNAs during and after treatment. Oncolytic virotherapy and nanotherapy are two neoteric methods that use various vectors to deliver microRNAs into cancer cells. Although these treatments have not yet entered into the clinical trials, much progress has been made in this area. Analyzing the expression profile of microRNAs after applying nanotherapy and oncolytic virotherapy can evaluate the effectiveness of these methods. This review refers to the studies conducted about these two approaches. The advantages and disadvantages of these methods in delivery and affecting microRNA expression patterns are discussed below.

Expression, Solubilization, Refolding and Final Purification of Recombinant Proteins as Expressed in the form of "Classical Inclusion Bodies" in E. coli.

Escherichia coli has been most widely used for production of the recombinant proteins. Over-expression of the recombinant proteins is the mainspring of the inclusion bodies formation. The refolding of these proteins into bioactive forms is cumbersome and partly time-consuming. In the present study, we reviewed and discussed most issues regarding the recovery of "classical inclusion bodies" by focusing on our previous experiences. Performing proper methods of expression, solubilization, refolding and final purification of these proteins, would make it possible to recover higher amounts of proteins into the native form with appropriate conformation. Generally, providing mild conditions and proper refolding buffers, would lead to recover more than 40% of inclusion bodies into bioactive and native conformation.

Synergistic effects of hydro extract of jujube fruit in combination with Mesalazine (orally) and Asacol (intra-colonic) administration in ameliorating animal model of ulcerative colitis / Efeitos sinérgicos do extrato aquoso da fruta da jujuba em combinação com administração de Mesalazina (via oral) e Asacol (intracolônico) na melhora de colite ulcerativa em modelo animal

ABSTRACT This study was done to investigate the synergistic impacts hydro extract of jujube fruit in combination with Mesalazine (orally) and Asacol (intra-colonic) administration in ameliorating animal model of ulcerative colitis (UC). After the induction of UC and with the development of signs, the treatment groups daily received the hydro extract of jujube fruit (200 mg/kg, orally, enema), Mesalazine (30 mg/kg, orally) and Asacol (10 mg/kg, enema). After 10 days, rats were euthanized and were studied. Findings indicated a significant increase in Myeloperoxidase (161.66 ± 10.40), Nitric oxide (216.01 ± 17.55), IL-6 (138.54 ± 7.02), and TNF-α (123.87 ± 9.80) colon tissue levels and pathological damage of positive control group compared with the negative control group. Hydro extract of jujube fruit in combination with Mesalazine (orally) and Asacol (intra-colonic) group represented a higher capability in significantly decreasing Myeloperoxidase (73.33 ± 9.07), Nitric oxide (81.66 ± 10.50), IL-6 (51.69 ± 5.19), TNF-α (30.59 ± 5.50) levels and pathological damage in compared with the other treatment groups. Considering accessibility and affordability of jujube fruit and the side effects of routine drugs, taking a combination of jujube fruit with low doses of routine pharmaceutical drugs can improve and cure ulcerative colitis disease.

RESUMO Este estudo foi realizado para investigar os impactos sinérgicos do extrato aquoso do fruto da jujuba em combinação com a administração de Mesalazina (por via oral) e Asacol (intracolônico) na melhora do modelo animal de colite ulcerativa. Após a indução da colite ulcerativa e com o desenvolvimento de sinais, os grupos de tratamento receberam diariamente o extrato aquoso do fruto da jujuba (200 mg/kg, via oral, enema), Mesalazina (30 mg/kg, via oral) e Asacol (10 mg/kg, enema). Após 10 dias, os ratos foram eutanasiados e estudados. Os achados indicaram um aumento significativo dos níveis de mieloperoxidase (161,66 ± 10,40), óxido nítrico (216,01 ± 17,55), IL-6 (138,54 ± 7,02) e TNF-α (123,87 ± 9,80) no tecido do cólon e dano patológico do grupo controle positivo comparado com o grupo controle negativo. O extrato aquoso da fruta de jujuba em combinação com Mesalazina (oral) e Asacol (intracolônico) representou maior capacidade de redução significativa dos níveis de mieloperoxidase (73,33 ± 9,07), óxido nítrico (81,66 ± 10,50), IL-6 (51,69 ± 5,19), TNF-α (30,59 ± 5,50) e dano patológico em comparação com os outros grupos de tratamento. Considerando a acessibilidade e disponibilidade do fruto da jujuba e dos efeitos colaterais dos medicamentos de rotina, tomar uma combinação de jujuba com baixas doses de medicamentos farmacêuticos de rotina pode melhorar e curar a colite ulcerativa.