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We determined cytokine levels in paired serum/CSF samples from first-episode schizophrenia (FES) participants (n = 20) and controls (n = 21) using a 13-plex immunoassay. Applying strictly-determined detection limits, 12 cytokines were found in serum and two in CSF. Higher serum MCP-1 levels (p = 0.007) were present in FES versus controls, which correlated with serum IgG (R = − 0.750; p = 0.013). Finally, IL-18 levels correlated with body weight in FES (R = 0.691; p = 0.041). This study demonstrates potential limitations in the sensitivity of multiplex cytokine assays for CSF studies in mental disorders and suggests that some published studies in this area should be re-evaluated.

We and others have observed reduced volumes of brain regions, including the nucleus accumbens, globus pallidus, hypothalamus, and habenula in opioid addiction. Notably, the insular cortex has been under increasing study in addiction, and a smaller anterior insula has been found in alcohol-addicted cases. Here, we have investigated whether similar effects occur in heroin addicts compared to healthy controls. Volumes of the anterior and posterior insula in heroin addicts (n = 14) and controls (n = 13) were assessed by morphometry of Nissl-myelin-stained serial whole-brain coronal sections. The mean relative volume of the anterior insular cortex was smaller than in non-addicted controls (3010 ± 614 *10–6 versus 3970 ± 1306 *10–6; p = 0.021). However, no significant differences in neuronal cell counts were observed. Therefore, the observed volume reduction appears to be a consequence of damaged connecting structures such as neuropil and glial cells. The findings were not confounded by age or duration of autolysis. Our results provide further evidence of structural deficits in key hubs of the addiction circuitry in heroin-dependent individuals and warrant further research in this area.

Background Males are more likely to die from COVID-19 than females. In addition, the mortality rate among positive and suspected COVID-19 patients were reported in many studies. The aim of this study is to evaluate the sex differential effect in the COVID-19 mortality by different age groups and polymerase chain reaction (PCR) test results. Research design In a multicenter cross-sectional study from 55 hospitals in Tehran, Iran, patients were categorized as positive, negative and suspected cases. Age group, sex and hospital wards were also assessed in the analysis. Results A total of 25481 cases (14791 males) were included in the study with a mortality rate of 12.0%. The mortality rates in positive, negative and suspected cases were 20.55%, 9.97% and 7.31%, respectively. Although the mortality in negative test group was considerable, sex was not associated with the death rate in this group. Using a Cox regression model, sex had a significant effect on the hazard of death due to COVID-19 in adult and senior male patients having positive and suspected PCR test results. However, sex was not found as significant factor for mortality in patients with a negative PCR test in different age groups. Conclusions Regardless of other risk factors, we found that the effect of sex on COVID-19 mortality varied significantly in different age groups. Therefore, appropriate strategies should be designed to protect adult and senior males from this deadly infectious disease. Furthermore, owing to the considerable death rate of COVID-19 patients with negative test results, new policies should be launched to increase the accuracy of diagnosis tests.

Background. Although vaccine rollout for COVID-19 has been effective in some countries, there is still an urgent need to reduce disease transmission and severity. We recently carried out a meta-analysis and found that pre- and in-hospital use of statins may improve COVID-19 mortality outcomes. Here, we provide an updated meta-analysis in an attempt to validate these results and increase the statistical power of these potentially important findings. Methods. The meta-analysis investigated the effect of observational and randomized clinical studies on intensive care unit (ICU) admission, tracheal intubation, and death outcomes in COVID-19 cases involving statin treatment, by searching the scientific literature up to April 23, 2021. Statistical analysis and random effect modeling were performed to assess the combined effects of the updated and previous findings on the outcome measures. Findings. The updated literature search led to the identification of 23 additional studies on statin use in COVID-19 patients. Analysis of the combined studies ( n = 47 ; 3,238,508 subjects) showed no significant effect of statin treatment on ICU admission and all-cause mortality but a significant reduction in tracheal intubation ( OR = 0.73 , 95% CI: 0.54-0.99, p = 0.04 , n = 10 studies). The further analysis showed that death outcomes were significantly reduced in the patients who received statins during hospitalization ( OR = 0.54 , 95% CI: 0.50-0.58, p < 0.001 , n = 7 studies), with no such effect of statin therapy before hospital admission ( OR = 1.06 , 95% CI = 0.82 -1.37, p = 0.670 , n = 29 studies). Conclusion. Taken together, this updated meta-analysis extends and confirms the findings of our previous study, suggesting that in-hospital statin use leads to significant reduction of all-cause mortality in COVID-19 cases. Considering these results, statin therapy during hospitalization, while indicated, should be recommended.

Cancer is one of the most frequent causes of worldwide death and morbidity and is a major public health problem. Although, there are several widely used treatment methods including chemo-, immune- and radiotherapies, these mostly lack sufficient efficiency and induce toxicities in normal surrounding tissues. Thus, finding new approaches to mitigate side effects and potentially accelerate treatment is paramount. In line with this, increasing preclinical evidence indicates that caloric restriction (CR) and fasting might have anticancer effects by reducing tumor progression, enhancing death of cancer cells, and elevating the effectiveness and tolerability of chemo- and radiotherapies. Nonetheless, clinical studies assessing the potential of CR and fasting in cancer are scarce and inconsistent, and more investigations are still required to clarify their effect in different aspects of cancer treatment. In this review, we have summarized the findings of preclinical and clinical studies of CR and fasting with respect to efficacy and on the adverse effects of standard cancer treatments.

Inflammatory diseases caused by infectious agents such as the SARS-CoV-2 virus can lead to impaired reductive-oxidative (REDOX) balance and disrupted mitochondrial function. Peripheral blood mononuclear cells (PBMCs) provide a useful model for studying the effects of inflammatory diseases on mitochondrial function but can be limited by the need to store these cells by cryopreservation prior to assay. Here, we describe a method for improving and determining PBMC viability with normalization of values to number of living cells. The approach can be applied not only to PBMC samples derived from patients with diseases marked by an altered inflammatory response such as viral infections.

COVID-19 disease is caused by infection with the SARS-CoV-2 virus and is associated with a cytokine storm effect in some patients. This can lead to decreased ability of the host to cope with the infection and result in severe disease outcomes. Here, we present a protocol for isolation of peripheral blood mononuclear cells (PBMCs) from COVID-19 patients followed by liquid chromatography-mass spectrometry (LC-MS) profiling to identify the affected molecules and molecular pathways. It is hoped that this will lead to the identification of potential biomarkers for monitoring the disease as well as treatment responses. This approach could also be used in the study of other respiratory viruses.

There is still an urgent need to develop effective treatments to help minimize the cases of severe COVID-19. A number of tools have now been developed and applied to address these issues, such as the use of non-contrast chest computed tomography (CT) for evaluation and grading of the associated lung damage. Here we used a deep learning approach for predicting the outcome of 1078 patients admitted into the Baqiyatallah Hospital in Tehran, Iran, suffering from COVID-19 infections in the first wave of the pandemic. These were classified into two groups of non-severe and severe cases according to features on their CT scans with accuracies of approximately 0.90. We suggest that incorporation of molecular and/or clinical features, such as multiplex immunoassay or laboratory findings, will increase accuracy and sensitivity of the model for COVID-19 -related predictions.

Multiplex assays that provide simultaneous measurement of multiple analytes in biological samples have now developed into widely used technologies in the study of diseases, drug discovery, and other medical areas. These approaches span multiple assay systems and can provide readouts of specific assay components with similar accuracy as the respective single assay measurements. Multiplexing allows the consumption of lower sample volumes, lower costs, and higher throughput compared with carrying out single assays. A number of recent studies have demonstrated the impact of multiplex assays in the study of the SARS-CoV-2 virus, the infectious agent responsible for the current COVID-19 pandemic. In this respect, machine learning techniques have proven to be highly valuable in capturing complex disease phenotypes and converting these insights into models which can be applied in real-world settings. This chapter gives an overview of opportunities and challenges of multiplexed biomarker analysis, with a focus on the use of machine learning aimed at identification of biological signatures for increasing our understanding of COVID-19 disease, and for improved diagnostics and prediction of disease outcomes.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent driving the current COVID-19 pandemic. The acute respiratory distress that occurs in some severe COVID-19 cases has been linked with hypercoagulation or thrombotic events as well as a worse prognosis and increased risk of death. Thus, point-of-care devices that can be used for early detection of coagulation abnormalities would assist in COVID-19 management. This chapter describes the use of the Roche Diagnostics CoaguChek

Approximately one in three people infected with the SARS-CoV-2 virus have mild symptoms or are asymptomatic. However, these individuals can still spread the virus. Regular self-testing can help to detect these individuals and thereby slow the spread and protect the more vulnerable members of society. Here, we present a protocol for use of the COVID-19 rapid antigen test which was made freely available to residents of the United Kingdom in April of this year. This using the lateral flow technique for detection of antigens and is amenable to multiplexing.

Since the original SARS-CoV-2 virus emerged from Wuhan, China, in late December 2019, a number of variants have arisen with enhanced infectivity, and some may even be capable of escaping the existing vaccines. Here we describe a rapid automated nucleic acid microarray hybridization and readout in less than 15 min using the Fraunhofer lab-on-a-chip platform for identification of bacterial species and antibiotic resistance. This platform allows a fast adaptation of new biomarkers enabling identification of different genes and gene mutations, such as those seen in the case the SARS-CoV-2 variants.

Severe cases of SARS-CoV-2 and other pathogenic virus infections are often associated with the uncontrolled release of proinflammatory cytokines, known as a "cytokine storm." We present a protocol for multiplex analysis of three cytokines, tumor necrosis factor-alpha (TNF-a), interleukin 6 (IL-6), and IL-10, which are typically elevated in cytokine storm events and may be used as a predictive biomarker profile of disease severity or disease course.

Blood serum or plasma proteins are potentially useful in COVID-19 research as biomarkers for risk prediction, diagnosis, stratification, and treatment monitoring. However, serum protein-based biomarker identification and validation is complicated due to the wide concentration range of these proteins, which spans more than ten orders of magnitude. Here we present a combined affinity purification-liquid chromatography mass spectrometry approach which allows identification and quantitation of the most abundant serum proteins along with the nonspecifically bound and interaction proteins. This led to the reproducible identification of more than 100 proteins that were not specifically targeted by the affinity column. Many of these have already been implicated in COVID-19 disease.

Due to continuous technical developments and new insights into the high complexity of infectious diseases such as COVID-19, there is an increasing need for multiplex biomarkers to aid clinical management and support the development of new drugs and vaccines. COVID-19 disease requires rapid diagnosis and stratification to enable the most appropriate treatment course for the best possible outcomes for patients. In addition, these tests should be rapid, specific, and sensitive. They should rule out other potential causes of illness with simultaneous testing for other diseases. Elevated levels of specific biomarkers can be used to establish severity risks of chronic diseases so that patients can be provided the proper medication at the right time. This review describes the state-of-the-art technologies in proteomics, transcriptomics, and metabolomics, for multiplex biomarker approaches in COVID-19 research.

Most people infected by the SARS-CoV-2 virus which causes COVID-19 disease experience mild or no symptoms. Severe forms of the disease are often marked by a hyper-inflammatory response known as a cytokine storm. Thus, biomarker tests which can identify these patients and place them on the appropriate treatment regime at the earliest possible phase would help to improve outcomes. Here we describe an automated microarray-based immunoassay using the Fraunhofer lab-on-a-chip platform for analysis of C-reactive protein due to its role in the hyper-inflammatory response.

SARS-CoV-2 can stimulate the expression of various inflammatory cytokines and induce the cytokine storm in COVID-19 patients leading to multiple organ failure and death. Curcumin as a polyphenolic compound has been shown to have anti-inflammatory properties and inhibit the release of numerous pro-inflammatory cytokines. We present multiplex analysis using the Evidence Investigator biochip system to determine the effect of curcumin on serum level of cytokines which are typically elevated in cytokine storm events, including tumor necrosis factor (TNF-α), interleukin 6 (IL-6), and IL-10.

Statins have pleiotropic effects on inflammatory responses in addition to their lipid-lowering action, which contributes to their favorable effect on cardiovascular disorders. Statins affect adhesion, migration, antigen presentation, and cytokine generation of immune cells. Pre-clinical and clinical studies suggest that statin intervention targeted early in the infection might help COVID-19 patients to reduce the effects of acute respiratory distress syndrome (ARDS), the cytokine storm, and vascular collapse by modulating harmful pathogenic mechanisms. This chapter presents a protocol for measuring blood-based biomarkers predictive of these responses in COVID-19 patients using two specific multiplex immunoassays that target proteins that differ widely in concentration.

The emergence of new SARS-CoV-2 variants has led to increased transmission and more severe cases of COVID-19, with some having the ability to escape the existing vaccines. This review discusses the importance of developing new vaccine strategies to keep pace with these variants to more effectively manage the pandemic. Many of the new vaccine approaches include multivalent display of the most highly mutated regions in the SARS-CoV-2 spike protein such that they resemble a virus particle and can stimulate an effective neutralization response. It is hoped that such approaches help to manage the existing pandemic and provide a robust infrastructure toward fast tracking responses across the world in case of future pandemics.

Infection with SARS-CoV-2, the causative agent of COVID-19, causes numerous cellular dysfunctions. The virus enters the host cells and hijacks the cell machinery for its replication, resulting in disturbances of the oxidative, reductive balance, increased production of damaging reactive oxygen species (ROS), and mitochondrial dysfunction. This damaging cycle can make cells less resistant to infection and make the host more likely to experience a severe disease course. Treatment with antioxidants has been tested as a potential approach to reduce the effects of this disorder. Here, we present a protocol to assess the impact of treatment with a mixture of curcuminoids on physiological and molecular biomarkers, focusing on determining total antioxidant capacity. We used a cohort of diabetes patients with an imbalance in redox mechanisms as such patients are more likely to become severely ill from COVID-19 than healthy persons.

COVID-19 disease caused by the novel SARS-CoV-2 virus represents a new challenge for healthcare systems. The molecular confirmation of infection is crucial to guide public health decision-making. This task could be made more difficult during the next influenza season. Thus, a rapid and user-friendly diagnostic test to discriminate SARS-CoV-2 from influenza viruses is urgently needed. Here, we present a multiplex quantitative polymerase chain reaction (qPCR) assay capable of distinguishing SARS-CoV-2 from influenza A and B cases. This assay benefits from the use of an inhibitor tolerant PCR mix which obviates the need for the rate-limiting extraction step, allowing for a more rapid and accurate analysis.

Quantitative polymerase chain reaction (qPCR) is a routinely used method for detection and quantitation of gene expression in real time. This is achieved through the incorporation and measurement of fluorescent reporter probes in the amplified cDNA strands, since the fluorescent signals increase as the reaction progresses. The availability of multiple probes which fluoresce at different wavelengths allows for multiplexing as this gives rise to amplicons with unique fluorescent signatures. Here we describe a method using the Inhibitor-Tolerant RT-qPCR kit, developed by Meridian Bioscience kit which allows simultaneous real-time quantitation of the UK, South Africa, and Brazil SARS-CoV-2 variants.

Background We recently reported increased levels of neutrophils, monocytes and C-reactive protein (CRP) correlated with symptom severity in acute schizophrenia. Here, we investigated if a similar pattern of innate immune system activation occurs in major depression (MD). Methods We assessed differential blood counts, CRP, depression symptoms (HAMD-21) and psychosocial functioning (GAF) in controls (n = 129) and patients with first (FEMD: n = 82) or recurrent (RMD: n = 47) disease episodes of MD at baseline (T0; hospital admission) and after 6-weeks treatment (T6). Results Considering smoking, BMI and gender as covariates, neutrophils (FEMD: p = 0.034, RMD: p = 0.034) and CRP (FEMD: p p = 0.021) were higher, and eosinophils (FEMD: p = 0.005, RMD: p = 0.004) lower in patients versus controls at T0. Baseline lymphocyte counts were elevated in RMD (p = 0.003) but not FEMD. Results were confirmed by analyses of nonsmokers. At follow-up, eosinophils rose significantly in FEMD (p = 0.011) but no significant changes were observed in RMD. Improvement in HAMD-21 correlated with T0–T6 changes of neutrophil counts in FEMD (r = 0.364, p = 0.024). Compared with our previous schizophrenia study, raised baseline neutrophil and reduced eosinophil counts in MD had smaller effect sizes and treatment had a weaker association with T0-T6 changes in neutrophils. In addition, lymphocytes were elevated at T0 in recurrent MD but not in schizophrenia patients. Conclusions These findings suggest that innate immunity may be involved in early stages of MD, and adaptive immunity may be involved in chronic disease. Thus, further studies may lead to new disease stage-dependent MD treatment strategies targeting different aspects of immune system activation.

Trehalose is a nonreducing disaccharide formed by two glucose molecules. It has been shown that trehalose can protect proteins and cellular membranes against the adverse effects of different types of stress, such as dehydration, cold, heat, and oxidation. Chronic liver disease has emerged as an important cause of morbidity and mortality throughout the world. This disaccharide has received attention for its hepatoprotective activities against liver damage. The main mechanisms underlying the hepatoprotective action of trehalose are reducing inflammatory signaling, enhancing antioxidant defense, and induction of autophagy.

The COVID-19 pandemic has plagued the world for more than 1 year now and has resulted in over 77 million cases and 1.7 million related deaths. While we await the rollout of the vaccines, new treatments are urgently needed to reduce the effects of this devastating virus. Here, we describe a number of preclinical studies which show promising effects of the polyphenol resveratrol.

Oxidative stress that occurs as a consequence of the imbalance between antioxidant activity and free radicals can contribute in the pathogenesis of metabolic disorders, such as type 2 diabetes mellitus (T2DM). Antioxidant therapies have been proposed as possible approaches to treat and attenuate diabetic complications. The purpose of this study was to evaluate potential antioxidant effects of trehalose on oxidative indices in a streptozotocin (STZ)-induced diabetic rat model.Diabetic rats were divided randomly into five treatment groups (six rats per group). One test group received 45 mg/kg/day trehalose via intraperitoneal injection, and another received 1.5 mg/kg/day trehalose via oral gavage for 4 weeks. Three control groups were also tested including nondiabetic rats as a normal control (NC), a nontreated diabetic control (DC), and a positive control given 200 mg/kg/day metformin. Levels of thiol groups (-SH), and serum total antioxidant capacity were measured between control and test groups. In addition, superoxide dismutase (SOD) and glutathione peroxidase (GPx) enzyme activities were assessed.In both oral and injection trehalose-treated groups, a marked increase was observed in serum total antioxidant capacity (TAC) (p 0.05) and thiol groups (-SH) (p 0.05). Also, SOD and GPx activities were increased after 4 weeks of treatment with trehalose.In conclusion, the present results indicate ameliorative effects of trehalose on oxidative stress, with increase antioxidant enzyme activities in STZ-induced diabetic rats.

Despite the ongoing vaccination efforts, there is still an urgent need for safe and effective treatments to help curb the debilitating effects of COVID-19 disease. This systematic review aimed to investigate the efficacy of supplemental curcumin treatment on clinical outcomes and inflammation-related biomarker profiles in COVID-19 patients. We searched PubMed, Scopus, Web of Science, EMBASE, ProQuest, and Ovid databases up to 30 June 2021 to find studies that assessed the effects of curcumin-related compounds in mild to severe COVID-19 patients. Six studies were identified which showed that curcumin supplementation led to a significant decrease in common symptoms, duration of hospitalization and deaths. In addition, all of these studies showed that the intervention led to amelioration of cytokine storm effects thought to be a driving force in severe COVID-19 cases. This was seen as a significant (p < 0.05) decrease in proinflammatory cytokines such as IL1β and IL6, with a concomitant significant (p < 0.05) increase in anti-inflammatory cytokines, including IL-10, IL-35 and TGF-α. Taken together, these findings suggested that curcumin exerts its beneficial effects through at least partial restoration of pro-inflammatory/anti-inflammatory balance. In conclusion, curcumin supplementation may offer an efficacious and safe option for improving COVID-19 disease outcomes. We highlight the point that future clinical studies of COVID-19 disease should employ larger cohorts of patients in different clinical settings with standardized preparations of curcumin-related compounds.

Approximately 30% of individuals with severe SARS-CoV-2 infections also develop neurological and psychiatric complaints. In rare cases, the occurrence of autoimmune encephalitis has been reported after SARS-CoV-2 infection. In this systematic review, we have identified eight SARS-CoV-2-associated cases of anti-NMDA receptor encephalitis. All had cerebrospinal fluid antibodies against the NMDA receptor and a recent onset of working memory deficits, altered mental status, or psychiatric symptoms, such as confusion, agitation, auditory hallucination, catatonia and speech dysfunction. All patients received high-dose steroid and immunoglobulin therapeutics and conditions improved in each case. These findings suggest that clinical attention should be paid to warning signs of autoimmune encephalitis in severe COVID-19 cases. If characteristic features of autoimmune encephalitis are present, autoantibody diagnostics should be performed and confirmed cases should be treated with immunotherapy to minimize neurological impairments. Supplementary Information The online version contains supplementary material available at 10.1186/s12974-021-02293-x.

Based on current implications of the SARS-CoV-2 pandemic with regards to mental health, we show that biological links exist between inflammation and mental illness in addition to psychoreactive effects. We describe key principles of the biological interaction of the immune system and the mind, as well as the possible routes of viral entry into the brain. In addition, we provide a stepwise scheme for the diagnosis and therapy of autoimmune-encephalitis with schizophrenia-like symptomatology as a general guide for clinical practice and in the specialized scenario of infections, such as those caused by the SARS-CoV-2 virus.

Diabetes mellitus is a chronic metabolic disorder characterized by persistent hyperglycemia. Traditional medicinal plants with antidiabetic properties can be used as drugs or dietary adjuvants to existing therapies. This chapter presents the preparation of aqueous and ethanol extracts of Adenosma bracteosum Bonati (A. bracteosum) and evaluation of these for antioxidant and α-glucosidase inhibition activities in vitro. In addition, we tested the extracts and the purified A. bracteosum compound (isoscutellarein 8-O-β-D-glucopyranoside) for antihyperglycemic effects in glucose-loaded hyperglycemic and streptozotocin (STZ)-induced diabetic mice.