Post-COVID-19 depression and serum interleukin 6 levels: A systematic review and meta-analysis of COVID-19 convalescents with and without depression.

OBJECTIVES: Depression is among the psychiatric sequelae of COVID-19, affecting more than 20% of the convalescents. Its underlying pathophysiology remains unclear. Interleukin 6 (IL-6), a pro-inflammatory cytokine, plays a critical role in the COVID-19-associated cytokine storm, has been implicated in depressive disorders, and may thus be involved in post-COVID-19 depression. METHODS: PubMed, Scopus, Embase, and Web of Science were systematically searched for relevant studies assessing peripheral IL-6 levels in convalescents who developed depression after COVID-19 vs. convalescents who did not. RESULTS: Five studies were included in our systematic review, and four entered the meta-analysis. The meta-analysis revealed that post-COVID people with de novo depression did not have statistically significant differences in IL-6 levels compared to those without depression (standardised mean difference (SMD) = 0.09, 95% confidence interval (CI) = -0.35, 0.54, p-value = 0.68). CONCLUSIONS: Although convalescents with depression did not have significantly higher IL-6 levels than convalescents without depression, the results should be interpreted considering the limited sample size and the low power of the included studies.

A systematic review, meta-analysis, and network analysis of diagnostic microRNAs in glaucoma.

Glaucoma is a chronic neurodegenerative process of the optic nerve that is the leading cause of blindness worldwide, and early diagnosis of the disease could greatly affect patients' prognoses. The pathophysiology of glaucoma is complicated by a combination of genetic and epigenetic factors. Deciphering the early diagnostic biomarkers in glaucoma could attenuate the disease's global burden and help us understand the exact mechanisms involved in glaucoma. The microRNAs are members of a larger family of non-coding RNAs that play an essential role in the epigenetic basis of glaucoma. A systematic study and meta-analysis of diagnostic microRNAs in glaucoma, jointly with network analysis of target genes, were carried out on published papers assessing differentially expressed microRNAs in human subjects. In total, 321 articles were found, and, after screening, six studies were eligible for further analysis. 52 differentially expressed microRNAs were found, of which 28 and 24 were up-regulated and down-regulated, respectively. Only 12 microRNAs were qualified for meta-analysis, with overall sensitivity and specificity of 80% and 74%, respectively. Then, using network analysis, it became apparent that the VEGF-A, AKT1, CXCL12, and HRAS genes were the most important targets for the microRNAs. Perturbations in WNT signaling, protein transport, and extracellular matrix organization pathways were discovered to be important in the etiology of glaucoma using the community detection approach. This study tries to uncover the promising microRNAs and their target genes that govern the epigenetics of glaucoma.

Antibiotics with Antiviral and Anti-Inflammatory Potential Against Covid-19: A Review.

In Covid-19 cases, elderly patients in long-term care facilities, children younger than five years with moderate symptoms, and patients admitted to ICU or with comorbidities are at a high risk of coinfection, as suggested by the evidence. Thus, in these patients, antibiotic therapy based on empirical evidence is necessary. Finding appropriate antimicrobial agents, especially with antiviral and anti-inflammatory properties, is a promising approach to target the virus and its complications, hyper-inflammation, and microorganisms resulting in co-infection. Moreover, indiscriminate use of antibiotics can be accompanied by Clostridioides difficile colitis, the emergence of resistant microorganisms, and adverse drug reactions, particularly kidney damage and QT prolongation. Therefore, rational administration of efficient antibiotics is an important issue. The main objective of the present review is to provide a summary of antibiotics with possible antiviral activity against SARS-CoV-2 and anti-immunomodulatory effects to guide scientists for further research. Besides, the findings can help health professionals in the rational prescription of antibiotics in Covid-19 patients with a high risk of co-infection.

Healing Field: Using Alternating Electric Fields to Prevent Cytokine Storm by Suppressing Clonal Expansion of the Activated Lymphocytes in the Blood Sample of the COVID-19 Patients.

In the case of the COVID-19 early diagnosis, numerous tech innovations have been introduced, and many are currently employed worldwide. But, all of the medical procedures for the treatment of this disease, up to now, are just limited to chemical drugs. All of the scientists believe that the major challenge toward the mortality of the COVID-19 patients is the out-of-control immune system activation and the subsequent cytokine production. During this process, the adaptive immune system is highly activated, and many of the lymphocytes start to clonally expand; hence many cytokines are also released. So, any attempt to harness this cytokine storm and calm down the immune outrage is appreciated. While the battleground for the immune hyperactivation is the lung ambient of the infected patients, the only medical treatment for suppressing the hypercytokinemia is based on the immunosuppressor drugs that systemically dampen the immunity with many unavoidable side effects. Here, we applied the alternating electric field to suppress the expansion of the highly activated lymphocytes, and by reducing the number of the renewed cells, the produced cytokines were also decreased. Applying this method to the blood of the COVID-19 patients in vitro showed ∼33% reduction in the average concentration of the three main cytokines after 4 days of stimulation. This method could carefully be utilized to locally suppress the hyperactivated immune cells in the lung of the COVID-19 patients without any need for systemic suppression of the immune system by the chemical drugs.

Human study on cancer diagnostic probe (CDP) for real-time excising of breast positive cavity side margins based on tracing hypoxia glycolysis; checking diagnostic accuracy in non-neoadjuvant cases.

BACKGROUND: Cancer diagnostic probe (CDP) had been developed to detect involved breast cavity side margins in real-time (Miripour et al. Bioeng Transl Med. e10236.). Here, we presented the results of the in vivo human model CDP studies on non-neoadjuvant cases. METHODS: This study is a prospective, blind comparison to a gold standard, and the medical group recruited patients. CDP and frozen data were achieved before the permanent pathology experiment. The main outcome of the study is surgical margin status. From November 2018 to April 2020, 202 patients were registered, and 188 were assigned for the study. Breast-conserving surgery at any age or gender, re-surgery due to re-currency, or involved margins are acceptable. Patients must be non-neoadjuvant. The reliability of CDP scoring had been evaluated by the pathology of the scored IMs. Then, three models of the study were designed to compare CDP with the frozen sections. Receiver operating characteristic (ROC) curves and AUC were measured based on the permanent postoperative pathology gold standard. RESULTS: A matched clinical diagnostic categorization between the pathological results of the tested IMs and response peaks of CDP on 113 cases, was reported (sensitivity = 97%, specificity = 89.3%, accuracy = 92%, positive predictive value (PPV) = 84.2%, and negative predictive value (NPV) = 98%). Study A showed the independent ability of CDP for IM scoring (sensitivity = 80%, specificity = 90%, accuracy = 90%, PPV = 22.2%, and NPV = 99.2%). Study B showed the complementary role of CDP to cover the missed lesions of frozen sections (sensitivity = 93.8%, specificity = 91%, accuracy = 91%, PPV = 55.6%, and NPV = 99.2%). Study C showed the ability of CDP in helping the pathologist to reduce his/her frozen miss judgment (specificity = 92%, accuracy = 93%, PPV = 42.1%, and NPV = 100%). Results were reported based on the post-surgical permanent pathology gold standard. CONCLUSION: CDP scoring ability in intra-operative margin detection was verified on non-neoadjuvant breast cancer patients. Non-invasive real-time diagnosis of IMs with pathological values may make CDP a distinct tool with handheld equipment to increase the prognosis of breast cancer patients.

Electrochemical tracing of hypoxia glycolysis by carbon nanotube sensors, a new hallmark for intraoperative detection of suspicious margins to breast neoplasia.

For most people, the first step in treatment is to take out the tumor (surgery), so precise and fast diagnosis of any sign of high-risk and neoplastic cells, especially in surgical cavity margins, is significant. The frozen pathology method is the conventional standard of intraoperative diagnosis, but the low number of slides prepared from non-fixed tissues prevents us from achieving a perfect diagnosis. Although many improvements in intraoperative margin detection were achieved, still real-time detection of neoplastic lesions is crucial to improving diagnostic quality. Functionalized carbon nanotubes grown on the electrode needles lively and selectively determine the H2O2 released from cancer/atypical cells through reverse Warburg effect and hypoxia assisted glycolysis pathways in a quantitative electrochemical manner. The study was carried out on cell lines, 57 in vivo mice models with breast cancer, and 258 fresh in vitro samples of breast cancer tumors. A real-time electrotechnical system, named cancer diagnostic probe (CDP) (US Patent Pub. No.: US 2018/02991 A1, US 2021/0007638 A1, and US 2021/0022650 A1 [publications], and US 10,786,188 B1 [granted]), has been developed to find pre-neoplastic/neoplastic cells in vivo in a quantitative electrochemical manner by tracing hypoxia glycolysis byproducts. Matched pathological evaluations with response peaks of CDP were found based on the presence of neoplasia (from atypia to invasive carcinoma) in live breast tissues. The ability of CDP to find neoplastic lesions in mice models in vivo and fresh breast tumors in vitro was verified with sensitivity and specificity of 95% and 97%, respectively. The system may help a surgeon assistant system for usage in the operating room after passing many trials and standard examinations in the future.

Antidepressants with anti-tumor potential in treating glioblastoma: A narrative review.

Glioblastoma multiforme (GBM) is known as the deadliest form of brain tumor. In addition, its high treatment resistance, heterogeneity, and invasiveness make it one of the most challenging tumors. Depression is a common psychological disorder among patients with cancer, especially GBM. Due to the high occurrence rates of depression in GBM patients and the overlap of molecular and cellular mechanisms involved in the pathogenesis of these diseases, finding antidepressants with antitumor effects could be considered as an affordable strategy for the treatment of GBM. Antidepressants exert their antitumor properties through different mechanisms. According to available evidence in this regard, some of them can eliminate the adverse effects resulting from chemo-radiotherapy in several cancers along with their synergistic effects caused by chemotherapy. Therefore, providing comprehensive insight into this issue would guide scientists and physicians in developing further preclinical studies and clinical trials, in order to evaluate antidepressants' antitumor potential. Considering that no narrative review has been recently published on this issue, specifically on these classes of drugs, we present this article with the purpose of describing the antitumor cellular mechanisms of three classes of antidepressants as follows: tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), and monoamine oxidase inhibitors (MAOIs) in GBM.

Capture-free deactivation of CTCs in the bloodstream; a metastasis suppression method by electrostatic stimulation of the peripheral blood.

While limited investigations have been reported on CTC elimination and its profits, recently, some new works were reported on detection followed by the destruction of CTCs. Limitations and complications of CTC capturing procedures have highly reduced the chance of selective destruction of CTCs in the bloodstream in the therapeutic guidelines of the patients. Here, we selectively deactivated the invasive function of CTCs during their circulation in the bloodstream by exposing the whole blood to pure positive electrostatic charge stimulation (PPECS). Our treatment suppressed pulmonary metastasis and extended the survival of the mice had been intravenously injected by electrostatically deactivated 4T1 breast cancer CTCs. Moreover, the number of cancerous lung nodules was drastically reduced in the mice injected by treated CTCs in comparison with the non-treated cohort. Evaluating the side effect of the PPECS on the blood components revealed no major effect on the functional properties of the white blood cells, and just a negligible fraction (∼10%) was damaged during this process. This approach does not need any capturing or targeting of CTCs from the blood as it is focused on perturbing the electrical function of negatively-charged tumor cells after being exposed to positive electrostatic charges. Taken together, continuous in-vivo deactivation of CTCs by PPECS with no requirement to complicated capturing protocols may improve the survival of cancer patients.

A label-free graphene-based impedimetric biosensor for real-time tracing of the cytokine storm in blood serum; suitable for screening COVID-19 patients.

Concurrent with the pandemic announcement of SARS-CoV-2 infection by the WHO, a variety of reports were published confirming the cytokine storm as the most mortal effect of the virus on the infected patients. Hence, cytokine storm as an evidenced consequence in most of the COVID-19 patients could offer a promising opportunity to use blood as a disease progression marker. Here, we have developed a rapid electrochemical impedance spectroscopy (EIS) sensor for quantifying the overall immune activity of the patients. Since during the cytokine storm many types of cytokines are elevated in the blood, there is no need for specific detection of a single type of cytokine and the collective behavior is just measured without any electrode functionalization. The sensor includes a monolayer graphene on a copper substrate as the working electrode (WE) which is able to distinguish between the early and severe stage of the infected patients. The charge transfer resistance (R CT) in the moderate and severe cases varies about 65% and 138% compared to the normal groups, respectively and a specificity of 77% and sensitivity of 100% based on ELISA results were achieved. The outcomes demonstrate a significant correlation between the total mass of the three main hypercytokinemia associated cytokines including IL-6, TNF-α and IFN-γ in patients and the R CT values. As an extra application, the biosensor's capability for diagnosis of COVID-19 patients was tested and a sensitivity of 92% and specificity of 50% were obtained compared to the RT-PCR results.

Real-time diagnosis of reactive oxygen species (ROS) in fresh sputum by electrochemical tracing; correlation between COVID-19 and viral-induced ROS in lung/respiratory epithelium during this pandemic.

COVID-19 is the shocking viral pandemics of this year which affected the health, economy, communications, and all aspects of social activities all over the world. Early diagnosis of this viral disease is very important since it can prevent lots of mortalities and care consumption. The functional similarities between COVID-19 and COVID-2 in inducing acute respiratory syndrome lightened our mind to find a diagnostic mechanism based on early traces of mitochondrial ROS overproduction as lung cells' dysfunctions induced by the virus. We designed a simple electrochemical sensor to selectively detect the intensity of ROS in the sputum sample (with a volume of less than 500 µl). Comparing the results of the sensor with clinical diagnostics of more than 140 normal and involved cases resulted in a response calibration with accuracy and sensitivity both 97%. Testing the sensor in more than 4 hospitals shed promising lights in ROS based real-time tracing of COVID-19 from the sputum sample.

Silicon nanowire based biosensing platform for electrochemical sensing of Mebendazole drug activity on breast cancer cells.

Electrochemical approaches have played crucial roles in bio sensing because of their Potential in achieving sensitive, specific and low-cost detection of biomolecules and other bio evidences. Engineering the electrochemical sensing interface with nanomaterials tends to new generations of label-free biosensors with improved performances in terms of sensitive area and response signals. Here we applied Silicon Nanowire (SiNW) array electrodes (in an integrated architecture of working, counter and reference electrodes) grown by low pressure chemical vapor deposition (LPCVD) system with VLS procedure to electrochemically diagnose the presence of breast cancer cells as well as their response to anticancer drugs. Mebendazole (MBZ), has been used as antitubulin drug. It perturbs the anodic/cathodic response of the cell covered biosensor by releasing Cytochrome C in cytoplasm. Reduction of cytochrome C would change the ionic state of the cells monitored by SiNW biosensor. By applying well direct bioelectrical contacts with cancer cells, SiNWs can detect minor signal transduction and bio recognition events, resulting in precise biosensing. Our device detected the trace of MBZ drugs (with the concentration of 2nM) on electrochemical activity MCF-7 cells. Also, experimented biological analysis such as confocal and Flowcytometry assays confirmed the electrochemical results.