Surveying haemoperfusion impact on COVID-19 from machine learning using Shapley values.

BACKGROUND: Haemoperfusion (HP) is an innovative extracorporeal therapy that utilizes special cartridges to filter the blood, effectively removing pro-inflammatory cytokines, toxins, and pathogens in COVID-19 patients. This retrospective cohort study aimed to assess the clinical benefits of HP for severe COVID-19 cases using Shapley values for machine learning models. METHODS: The research involved 578 inpatients (≥ 20 years old) admitted to Baqiyatallah hospital (Tehran, Iran). The control group (359 patients) received standard treatment, including high doses of corticosteroids (a single 500 mg methylprednisolone pulse, followed by 250 mg for 2 days), categorized as regimen (I). On the other hand, the HP group (219 patients) received regimen II, consisting of the same corticosteroid treatment (regimen I) along with haemoperfusion using Cytosorb H300. The frequency of haemoperfusion sessions varied based on the type of lung involvement determined by chest CT scans. In addition, the value function v defines the Shapley value of the i th feature for the query point x , where the input matrix features represent individual characteristics, drugs, and history and clinical conditions of the patient. RESULTS: Our data showed a favorable clinical response in the HP group compared to the control group. Notably, one-to-three sessions of HP using the CytoSorb® 300 cartridge led to reduced ventilation requirements and mortality rates in severe COVID-19 patients. Shapley values were calculated to evaluate the contribution of haemoperfusion among other factors, such as side effects, medications, and individual characteristics, to COVID-19 patient outcomes. In addition, there is a significant difference between the two groups among the treatments and medications used remdesivir, adalimumab, tocilizumab, favipiravir, Interferon beta-1a, enoxaparin prophylaxis, enoxaparin full dose, heparin prophylaxis, and heparin full dose (P < 0.05). It seems that haemoperfusion has a positive impact on the reduction of inflammation markers and renal functional such as ferritin and creatinine, respectively, as well as D-dimer and WBC levels in the HP group were significantly lower than the control group. CONCLUSION: The findings indicated that haemoperfusion played a crucial role in predicting patient survival, making it a significant feature in classifying patients' prognoses.

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.

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.

Gastrointestinal cancers, ACE-2/TMPRSS2 expression and susceptibility to COVID-19.

Recent studies on the pathophysiology of COVID-19 are indicating that the Angiotensin convertase enzyme 2 (ACE-2) and transmembrane serine protease 2 (TMPRSS2) can act as a major component in the fusion of SARS-Cov-2 with target cells. It has also been observed that the expression of ACE-2 and TMPRSS2 can be altered in malignancies. Shedding light on this matter could be crucial since the COVID-19 pandemic interfered with many gastrointestinal cancer screening programs. Herein we discuss the possibility of severe forms of COVID-19 in patients with gastrointestinal cancers due to the gastrointestinal entry route of SARS-CoV-2 into the human body. The disruption of cancer screening programs caused by the current COVID-19 pandemic could therefore have massive negative health impact on patients affected by gastrointestinal malignancies.

The effects of oxygen-ozone therapy on regulatory T-cell responses in multiple sclerosis patients.

Multiple sclerosis (MS) is a common degenerative disorder of the central nervous system. The decreased frequency and dysfunction of Treg cells cause inflammation and disease progression. Ozone autohemotherapy can be used as a potential therapeutic approach to regulate the immune system responses and inflammation in MS. For this purpose, 20 relapsing-remitting multiple sclerosis patients were under treatment with ozone twice weekly for 6 months. The frequency of Treg cell, the expression levels of the Treg cell-related factors (FoxP3, IL-10, TGF-ß, miR-17, miR-27, and miR-146A), and the secretion levels of IL-10 and TGF-ß were assessed. We found a significant increase in the number of Treg cells, expression levels of FoxP3, miRNAs (miR-17 and miR-27), IL-10, and TGF-ß factors in patients after oxygen-ozone (O2 -O3 ) therapy compared to before treatment. In contrast, oxygen-ozone therapy notably decreased the expression level of miR-146a in treated patients. Interestingly, the secretion levels of both IL-10 and TGF-ß cytokines were considerably increased in both serum and supernatant of cultured peripheral blood mononuclear cells in posttreatment condition compared to pretreatment condition. According to results, oxygen-ozone therapy raised the frequency of Treg cell and its relevant factors in treated MS patients. Oxygen-ozone therapy would contribute to improving the MS patients by elevating the Treg cell responses.

The Primary Outcomes and Epidemiological and Clinical Features of Coronavirus Disease 2019 (COVID-19) in Iran.

AIM: We aimed to describe the epidemiological and clinical characteristics of Iranian patients with COVID-19. METHODS: In this single-center and retrospective study, patients with confirmed COVID-19 infections were enrolled. Univariate and multivariate logistic regression methods were used to explore the risk factors associated with outcomes. RESULTS: Of 179 patients with confirmed COVID-19 infection, 12 remained hospitalized at the end of the study and 167 were included in the final analysis. Of these, 153 (91.6%) were discharged and 14 (8.38%) died in hospital. Approximately half (50.9%) of patients suffered from a comorbidity, with diabetes or coronary heart disease being the most common in 20 patients. The most common symptoms on admission were fever, dyspnea, and cough. The mean durations from first symptoms to hospital admission was 8.64 ± 4.14 days, whereas the mean hospitalization time to discharge or death was 5.19 ± 2.42 and 4.35 ± 2.70 days, respectively. There was a significantly higher age in non-survivor patients compared with survivor patients. Multivariate regression showed increasing odds ratio (OR) of in-hospital death associated with respiratory rates >20 breaths/min (OR: 5.14, 95% CI: 1.19-22.15, p = 0.028) and blood urea nitrogen (BUN) >19 mg/dL (OR: 4.54, 95% CI: 1.30-15.85, p = 0.017) on admission. In addition, higher respiratory rate was associated with continuous fever (OR: 4.08, 95% CI: 1.18-14.08, p = 0.026) and other clinical symptoms (OR: 3.52, 95% CI: 1.05-11.87, p = 0.04). CONCLUSION: The potential risk factors including high respiratory rate and BUN levels could help to identify COVID-19 patients with poor prognosis at an early stage in the Iranian population.

The molecular epidemiology of respiratory viruses in military trainees in Iran.

Background: Military populations are more prone to respiratory infections worldwide. There is a dearth of research about the role of viral pathogens in the etiology of respiratory infections in military trainees in Iran. Hence, we aimed to investigate the molecular epidemiology and clinical symptoms of respiratory viruses among this population. Methods: This cross-sectional study was performed on 400 military trainees with symptoms of respiratory infection, referred to the military medical clinic center in the basic military training camp of the General Staff of the Armed Forces of the Islamic Republic of Iran. Nucleic acid extraction from the throat or nasopharyngeal swab samples was performed by an automated extraction system. The extracts were then analyzed by the CLART® PneumoVir array system for the detection of respiratory viruses. Results: All military trainees were male, aged between 18 and 57 years (mean: 21.69 years). Sore throat (75.5%), rhinorrhea (63.2%), cough (59.2%), fever (59.2%), and nasal congestion (50.5%) were amongst the most common symptoms. Overall, viral pathogens were detected in a total count of 124 (31%). The most commonly detected viruses were rhinovirus (7.2%), respiratory syncytial virus A (7.2%) and influenza B virus (6%). Conclusion: This study was an important first step for understanding the etiological role of viral pathogens in respiratory infection among military trainees population in Iran. Our results indicated that rhinovirus, respiratory syncytial virus A and influenza B virus are important viral pathogens causing respiratory infection in military trainees, respectively. However, further multi-center studies with larger sample size are strongly recommended to confirm our findings.

Therapeutic relevance of ozone therapy in degenerative diseases: Focus on diabetes and spinal pain.

Ozone, one of the most important air pollutants, is a triatomic molecule containing three atoms of oxygen that results in an unstable form due to its mesomeric structure. It has been well-known that ozone has potent ability to oxidize organic compounds and can induce respiratory irritation. Although ozone has deleterious effects, many therapeutic effects have also been suggested. Since last few decades, the therapeutic potential of ozone has gained much attention through its strong capacity to induce controlled and moderated oxidative stress when administered in precise therapeutic doses. A plethora of scientific evidence showed that the activation of hypoxia inducible factor-1α (HIF-1a), nuclear factor of activated T-cells (NFAT), nuclear factor-erythroid 2-related factor 2-antioxidant response element (Nrf2-ARE), and activated protein-1 (AP-1) pathways are the main molecular mechanisms underlying the therapeutic effects of ozone therapy. Activation of these molecular pathways leads to up-regulation of endogenous antioxidant systems, activation of immune functions as well as suppression of inflammatory processes, which is important for correcting oxidative stress in diabetes and spinal pain. The present study intended to review critically the available scientific evidence concerning the beneficial properties of ozone therapy for treatment of diabetic complications and spinal pain. It finds benefit for integrating the therapy with ozone into pharmacological procedures, instead of a substitutive or additional option to therapy.

Antimicrobial activity of eugenol and essential oils containing eugenol: A mechanistic viewpoint.

Eugenol is a hydroxyphenyl propene, naturally occurring in the essential oils of several plants belonging to the Lamiaceae, Lauraceae, Myrtaceae, and Myristicaceae families. It is one of the major constituents of clove (Syzygium aromaticum (L.) Merr. & L.M. Perry, Myrtaceae) oil and is largely used in both foods and cosmetics as a flavoring agent. A large body of recent scientific evidence supports claims from traditional medicine that eugenol exerts beneficial effects on human health. These effects are mainly associated with antioxidant and anti-inflammatory activities. Eugenol has also shown excellent antimicrobial activity in studies, being active against fungi and a wide range of gram-negative and gram-positive bacteria. The aim of this review is to analyze scientific data from the main published studies describing the antibacterial and antifungal activities of eugenol targeting different kind of microorganisms, such as those responsible for human infectious diseases, diseases of the oral cavity, and food-borne pathogens. This article also reports the effects of eugenol on multi-drug resistant microorganisms. On the basis of this collected data, eugenol represents a very interesting bioactive compound with broad spectrum antimicrobial activity against both planktonic and sessile cells belonging to food-decaying microorganisms and human pathogens.

Protective Effect of Ozone against Hemiscorpius lepturus Envenomation in Mice.

OBJECTIVE: Scorpion (Hemiscorpius lepturus) stings are a public health concern in Iran, particularly in south and southwestern regions of Iran. The gold standard for the treatment of a scorpion sting is anti-venom therapy. However, immunotherapy can have serious side effects, such as anaphylactic shock (which can sometimes even lead to death). The aim of the current study was to demonstrate the protective effect of ozone against toxicity induced by Hemiscorpius lepturus (H. lepturus) venom in mice. METHODS: Eight hours after the injection of ozone to the experimental design groups, the male mice were decapitated and mitochondria were isolated from five different tissues (liver, kidney, heart, brain, and spinal cord) using differential ultracentrifugation. Then, assessment of mitochondrial parameters including mitochondrial reactive oxidative species (ROS) production, mitochondrial membrane potential (MMP), ATP level, and the release of cytochrome c from the mitochondria was performed. RESULTS: Our results showed that H. lepturus venom-induced oxidative stress is related to ROS production and MMP collapse, which is correlated with cytochrome c release and ATP depletion, indicating the predisposition to the cell death signaling. CONCLUSION: In general, ozone therapy in moderate dose can be considered as clinically effective for the treatment of H. lepturus sting as a protective and antioxidant agent.

Effect of the Cardio First Angel™ device on CPR indices: a randomized controlled clinical trial.

BACKGROUND: A number of cardiopulmonary resuscitation (CPR) adjunct devices have been developed to improve the consistency and quality of manual chest compressions. We investigated whether a CPR feedback device would improve CPR quality and consistency, as well as patient survival. METHODS: We conducted a randomized controlled study of patients undergoing CPR for cardiac arrest in the mixed medical-surgical intensive care units of four academic teaching hospitals. Patients were randomized to receive either standard manual CPR or CPR using the Cardio First Angel™ CPR feedback device. Recorded variables included guideline adherence, CPR quality, return of spontaneous circulation (ROSC) rates, and CPR-associated morbidity. RESULTS: A total of 229 subjects were randomized; 149 were excluded; and 80 were included. Patient demographics were similar. Adherence to published CPR guidelines and CPR quality was significantly improved in the intervention group (p < 0.0001), as were ROSC rates (72 % vs. 35 %; p = 0.001). A significant decrease was observed in rib fractures (57 % vs. 85 %; p = 0.02), but not sternum fractures (5 % vs. 17 %; p = 0.15). CONCLUSIONS: Use of the Cardio First Angel™ CPR feedback device improved adherence to published CPR guidelines and CPR quality, and it was associated with increased rates of ROSC. A decrease in rib but not sternum fractures was observed with device use. Further independent prospective validation is warranted to determine if these results are reproducible in other acute care settings. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02394977 . Registered on 5 Mar 2015.

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 were 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 level of nitric oxide.

Association of norepinephrine with pressure ulcer development in critically ill patients with COVID-19-related acute respiratory distress syndrome: A dose-response analysis.

OBJECTIVES: To investigate the correlation between varying doses of norepinephrine (NE) and the incidence of pressure injuries (PIs) in COVID-19 patients in intensive care units (ICUs). DESIGN: A retrospective multicenter study was conducted on 1,078 COVID-19 patients admitted to ICUs with acute respiratory distress syndrome (ARDS) requiring mechanical ventilation. The research spanned from March 2020 to April 2021 across five university-affiliated hospitals in Iran. Univariate and multivariate binary logistic regression analyses, along with linear and non-linear dose-response assessments, were utilized to evaluate the relationship between NE dosages and the probability of PI development. FINDINGS: The multivariate analysis revealed a significant association between higher doses of NE administered over 24 h (OR: 1.832, 95 % CI: 1.218-2.754, P=0.004) and cumulative doses (OR: 1.408, 95 % CI: 1.204-1.975, P=0.048) with the occurrence of PIs. Moreover, patients receiving high NE doses had a nearly fourfold increased risk of developing PIs, regardless of PIs stage, compared to those on low or moderate doses (>15 µg/min vs. ≤ 15 µg/min; OR: 4.401, 95 % CI: 3.339-5.801, P=0.001). Although the linear dose-response analysis did not show a significant correlation between NE doses (µg/min) and PI development (P>0.05), the non-linear analysis indicated that NE doses ≤ 9 µg/min were associated with a reduced risk of PI development. CONCLUSION: Maintaining NE infusion within the range of 1-9 µg/min appears to be most effective in reducing the likelihood of PIs in ICU patients with COVID-19. Lower NE doses (≤9 µg/min) were associated with a lower risk of PI development, suggesting that factors beyond NE dosage or the use of other vasopressors may play a crucial role in PI formation in this patient cohort. IMPLICATIONS FOR CLINICAL PRACTICE: Rather than suggesting a specific threshold, clinicians should consider further studies to determine the optimal dose that balances microvascular perfusion and patient outcomes. It is crucial to comprehensively evaluate additional factors and selectively use vasopressors. Individualized care, including regular monitoring and personalized treatment plans, is essential for achieving the best outcomes in this patient population.

Effect of Ozone Therapy on Diabetes-related Foot Ulcer Outcomes: A Systematic Review and Meta-analysis.

PURPOSE: This study aimed to assess the effectiveness of ozone therapy in treating Diabetes-related Foot Ulcer (DFU) and its outcomes. METHODS: A systematic search was conducted in PubMed/MEDLINE, Scopus, Web of Science, and ProQuest databases for published studies evaluating the use of ozone as an adjunct treatment for DFU, from inception to December 21, 2022. The primary outcome measure was the change in wound size after the intervention compared to pretreatment. Secondary outcomes included time to complete ulcer healing, number of healed patients, adverse events, amputation rates, and hospital length of stay. Quantitative data synthesis for the meta-analysis was performed using a random-effects model and generic inverse variance method, while overall heterogeneity analysis was conducted using a fixed-effects model. Interstudy heterogeneity was assessed using the I2 index (>50%) and the Cochrane Q statistic test. Sensitivity analysis was performed using the leave-one-out method. RESULTS: The meta-analysis included 11 studies comprising 960 patients with DFU. The results demonstrated a significant positive effect of ozone therapy on reducing foot ulcer size (Standardized Mean Difference (SMD): -25.84, 95% CI: -51.65 to -0.04, p = 0.05), shortening mean healing time (SMD: -38.59, 95% CI: -51.81 to -25.37, p < 0.001), decreasing hospital length of stay (SMD: -8.75, 95% CI: -14.81 to -2.69, p < 0.001), and reducing amputation rates (Relative Risk (RR): 0.46, 95% CI: 0.30-0.71, p < 0.001), compared to standard treatment. CONCLUSION: This meta-analysis indicates that ozone therapy has additional benefits in expediting complete DFU healing, reducing the amputation rates, and decreasing hospital length of stay, though its effects do not differ from standard treatments for complete ulcer resolution. Further research is needed to address the heterogeneity among studies and to better understand the potential beneficial effects of ozone therapy.

Reduce the risk of ventilator-associated pneumonia in ICU patients by Ozonated water mouthwash: A double-blind randomized clinical trial.

BACKGROUND: The aim of this study was to compare the 2 mouthwash solutions, including chlorhexidine (CHG) and ozonated water (OZW) to reduce the risk of ventilator-associated pneumonia (VAP) in patients on mechanical ventilation in intensive care unit (ICU). METHODS: This randomized double-blind clinical trial was performed in ICU units of hospitals. Patients (n=73) were selected and divided into 2 groups of CHG (n=37) and OZW mouthwash (n=36). Mouthwash was performed by trained nurses. Chi-square test, independent t-test, paired t-test, Mann-Whitney U-test, and Repeated Measure ANOVA was used to evaluate the effect of CHG and OZW mouthwash on the risk of VAP occurrence by Clinical Pulmonary Infection Score (CPIS) checklists and swab culture. RESULTS: Both CHG and OZW mouthwash reduced the risk of VAP differ at different time points (the first, the third and the fifth days). There was also difference in the incidence of VAP in terms of culture of pulmonary secretions in the 2 groups. Incidence of VAP in the CHG mouthwash group was 45.9%, and also 25% in the OZW mouthwash group. Most pathogens, that found in the culture of pulmonary secretions in the CHG mouthwash was Acinetobacter baumannii; also, in the OZW mouthwash, A baumannii and Pseudomonas aeruginosa were the most frequent ones. CONCLUSIONS: OZW mouthwash was more effective than CHG mouthwash to reduce the risk of VAP.

Potential therapeutic applications of extracellular vesicles in the immunopathogenesis of COVID-19.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the cause of coronavirus disease 2019 (COVID-19) which has emerged as a global health crisis. Recently, more than 50 different types of potential COVID-19 vaccines have been developed to elicit a strong immune response against SARS-CoV-2. However, genetic mutations give rise to the new variants of SARS-CoV-2 which is highly associated with the reduced effectiveness of COVID-19 vaccines. There is still no efficient antiviral agent to specifically target the SARS-CoV-2 infection and treatment of COVID-19. Therefore, understanding the molecular mechanisms underlying the pathogenesis of SARS-CoV-2 may contribute to discovering a novel potential therapeutic approach to the management of COVID-19. Recently, extracellular vesicle (EV)-based therapeutic strategies have received great attention on account of their potential benefits in the administration of viral diseases. EVs are extracellular vesicles containing specific biomolecules which play an important role in cell-to-cell communications. It has been revealed that EVs are involved in the pathogenesis of different inflammatory diseases such as cancer and viral infections. EVs are released from virus-infected cells which could mediate the interaction of infected and uninfected host cells. Hence, these extracellular nanoparticles have been considered a novel approach for drug delivery to mediate the treatment of a wide range of diseases including, COVID-19. EVs are considered a cell-free therapeutic strategy that could ameliorate the cytokine storm and its complications in COVID-19 patients. Furthermore, EV-based cargo delivery such as immunomodulatory agents in combination with antiviral drugs may have therapeutic benefits in patients with SARS-CoV-2 infection. In this review, we will highlight the potential of EVs as a therapeutic candidate in the diagnosis and treatment of COVID-19. Also, we will discuss the future perspectives regarding the beneficial effects of Evs in the development of COVID-19 vaccines.

Exosomes from Adipose Tissue-derived Mesenchymal Stem Cells Induce Regulatory T Cells in COVID-19 Patients.

An imbalance between regulatory T (Treg) and T-helper (Th)-17 cells has been implicated in the pathogenesis of coronavirus disease 2019 (COVID-19). Mesenchymal stem cells (MSCs) exert immunomodulatory properties through secreting exosomes. This study aimed to assess the effect of MSC-derived exosomes (MSC-Exo) on the differentiation of peripheral blood mononuclear cells (PBMCs) into  Tregs from patients with COVID-19. Exosomes were isolated from adipose tissue-derived MSCs. PBMCs were separated from the whole blood of COVID-19 patients (n=20). Treg frequency was assessed before and 48 hours after treatment of PBMCs with MSC-Exo using flow cytometry. Expression of FOXP3 and cytokine genes, and the concentration of cytokines associated with Tregs, were assessed before and after treatment with MSC-Exo. The frequency of CD4+CD25+CD127-  Tregs was significantly higher after treating PBMCs with MSC-Exo (6.695±2.528) compared to before treatment (4.981±2.068). The expressions of transforming growth factor (TGF)-ß1, interleukin (IL)-10, and FOXP3 were significantly upregulated in MSC-Exo-treated PBMCs. The concentration of IL-10 increased significantly after treatment (994.7±543.9 pg/mL) of PBMCs with MSC-Exo compared with before treatment (563.5±408.6 pg/mL). The concentration of TGF-ß was significantly higher in the supernatant of PBMCs after treatment with MSC-Exo (477.0±391.1 pg/mL) than PBMCs before treatment (257.7±226.3 pg/mL). MSC-Exo has the potential to raise anti-inflammatory responses by induction of  Tregs, potentiating its therapeutic effects in COVID-19.

Oncolytic viruses: A novel treatment strategy for breast cancer.

Breast cancer, an unceasingly occurring neoplasm, is one of the major determinants of mortality in women. Several ineffective attempts have been pursued using with conventional therapies against breast cancer. Resistance to existing therapies and their respective debilitating adverse effects have led research toward a new era of cancer treatment using viruses. Virotherapy constitutes a developing treatment modality with multiple mechanisms of therapeutic activity in which the viruses can be directly oncolyticand can express transgenes or induce host immune response against tumor cells. Several different DNA- and RNA-containing viruses have been considered for virotherapy of breast cancer including adenovirus, herpes virus, vaccinia, reovirus, Newcastle Disease virus, measles virus and vesicular stomatitis virus. This review aims to summarize the viro-therapeutical agents against breast malignancies. Key Scientific Concepts of Review: In this review paper, we proposed a new strategy to virus's combinatorial treatments using several kinds of transgenes and drugs. These recombinant viruses have provided evidence of treatment efficacy against human breast cancer.