Soluble terminal complement complex blood levels are elevated in schizophrenia.

The role of the complement system in schizophrenia (Sz) is inconclusive due to heterogeneity of the disease and study designs. Here, we assessed the levels of complement activation products and functionality of the classical pathway in acutely ill unmedicated Sz patients at baseline and after 6 weeks of treatment versus matched controls. The study included analyses of the terminal complement complex (sTCC) and C5a in plasma from 96 patients and 96 controls by enzyme-linked immunosorbent assay. Sub-group analysis of serum was conducted for measurement of C4 component and activity of the classical pathway (28 and 24 cases per cohort, respectively). We found no differences in levels of C5a, C4 and classical pathway function in patients versus controls. Plasma sTCC was significantly higher in patients [486 (392-659) ng/mL, n = 96] compared to controls [389 (304-612) ng/mL, n = 96] (p = 0.027, δ = 0.185), but not associated with clinical symptom ratings or treatment. The differences in sTCC between Sz and controls were confirmed using an Aligned Rank Transformation model considering the covariates age and sex (p = 0.040). Additional analysis showed that sTCC was significantly associated with C-reactive protein (CRP; p = 0.006). These findings suggest that sTCC plays a role in Sz as a trait marker of non-specific chronic immune activation, as previously described for CRP. Future longitudinal analyses with more sampling time points from early recognition centres for psychoses may be helpful to better understand the temporal dynamics of innate immune system changes during psychosis development.

Naturalistic comparison of clomethiazole and Diazepam treatment in alcohol withdrawal: effects on oxidative stress, inflammatory cytokines and hepatic biomarkers.

Ethanol is metabolized by alcohol dehydrogenase to acetaldehyde and induces cytochrome P450 2E1 (CYP2E1), which generates reactive oxygen species that cause inflammatory liver damage. Clomethiazole, a drug approved for alcohol withdrawal treatment (AWT) in some European countries, inhibits CYP2E1. We hypothesized that clomethiazole would lead to a faster reduction in oxidative stress, inflammatory cytokines, and liver enzymes compared to diazepam treatment. We analysed respective biomarkers in 50 patients undergoing AWT and 25 healthy individuals but found no statistical difference between the two medication groups over 3-5 days. Hence, our hypothesis was not confirmed during this observation period.

Cytokine alterations in CSF and serum samples of patients with a first episode of schizophrenia: results and methodological considerations.

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.

Reduced anterior insular cortex volume in male heroin addicts: a postmortem study.

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.

Long-Term Vaccination and Treatment Strategies for COVID-19 Disease and Future Coronavirus Pandemics.

The appearance of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with increased infectivity and immune escape capabilities has allowed continuation of the COVID-19 pandemic for the foreseeable future. This review describes the worldwide efforts aimed at developing new vaccination and treatment strategies to keep pace with these variants as they emerge. In the case of vaccines and monoclonal antibody-based therapeutics, we describe the development of variant-specific, multivalent, and universal coronavirus directed approaches. Existing treatment approaches consist of repurposed medicines, such as antiviral compounds and anti-inflammatory agents, although efforts are underway to develop new ways of preventing or minimizing the effects of infection with the use of small molecules that disrupt binding the SARS-CoV-2 virus to host cells. Finally, we discuss the preclinical and clinical testing of natural products from medicinal herbs and spices, which have demonstrated anti-inflammatory and antiviral properties and therefore show potential as novel and safe COVID-19 treatment approaches.

The COVID-19 Pandemic: SARS-CoV-2 Structure, Infection, Transmission, Symptomology, and Variants of Concern.

Since it was first detected in December 2019, the COVID-19 pandemic has spread across the world and affected virtually every country and territory. The pathogen driving this pandemic is SARS-CoV-2, a positive-sense single-stranded RNA virus which is primarily transmissible though the air and can cause mild to severe respiratory infections in humans. Within the first year of the pandemic, the situation worsened with the emergence of several SARS-CoV-2 variants. Some of these were observed to be more virulent with varying capacities to escape the existing vaccines and were, therefore, denoted as variants of concern. This chapter provides a general overview of the course of the COVID-19 pandemic up to April 2022 with a focus on the structure, infection, transmission, and symptomology of the SARS-CoV-2 virus. The main objectives were to investigate the effects of the variants of concern on the trajectory of the virus and to highlight a potential pathway for coping with the current and future pandemics.

Rapid Detection of SARS-CoV-2 Variants of Concern by Genomic Surveillance Techniques.

This chapter describes the application of genomic, transcriptomic, proteomic, and metabolomic methods in the study of SARS-CoV-2 variants of concern. We also describe the important role of machine learning tools to identify the most significant biomarker signatures and discuss the latest point-of-care devices that can be used to translate these findings to the physician's office or to bedside care. The main emphasis is placed on increasing our diagnostic capacity and predictability of disease outcomes to guide the most appropriate treatment strategies.

The Relationship Between Psoriasis, COVID-19 Infection and Vaccination During Treatment of Patients.

Since the outbreak of the COVID-19 pandemic in December 2019, scientists worldwide have been looking for a way to control this global threat. One of the most successful and practical solutions has been the development and worldwide distribution of the COVID-19 vaccines. However, in a small percentage of cases, vaccination can lead to de novo development or exacerbation of immune or inflammatory conditions such as psoriasis. Due to the immunomodulatory nature of this disease, people affected by psoriasis and other related skin conditions have been encouraged to receive COVID-19 vaccines, which are immunomodulatory by nature. As such, dermatological reactions are possible in these patients, and cases of onset, exacerbation or change in the type of psoriasis have been observed in patients administered with COVID-19 vaccines. Considering the rarity and minor nature of some of these cutaneous reactions to COVID-19 vaccination, there is a general consensus that the benefits of vaccination outweigh the potential risks of experiencing such side effects. Nevertheless, healthcare workers who administer vaccines should be made aware of the potential risks and advise recipients accordingly. Furthermore, we suggest careful monitoring for potentially deleterious autoimmune and hyperinflammatory responses using point-of-care biomarker monitoring.

Spices and Biomarkers of COVID-19: A Mechanistic and Therapeutic Perspective.

In the face of the COVID-19 pandemic, many people around the world have increased their healthy behaviors to prevent transmission of the virus and potentially improve their immune systems. Therefore, the role of diet and food compounds such as spices with bioactive and antiviral properties may be important in these efforts. In this chapter, we review the efficacy of spices such as turmeric (curcumin), cinnamon, ginger, black pepper, saffron, capsaicin, and cumin by investigating the effects of these compounds of COVID-19 disease severity biomarkers.

Antiviral Mechanisms of Curcumin and Its Derivatives in Prevention and Treatment of COVID-19: A Review.

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has now plagued the world for almost 3 years. Although vaccines are now available, the severity of the pandemic and the current dearth of approved effective medications have prompted the need for novel treatment approaches. Curcumin, as a food nutraceutical with anti-inflammatory and antioxidant effects, is now under consideration for the prevention and treatment of COVID-19. Curcumin has been demonstrated to retard the entrance of SARS-CoV-2 into cells, interfere with its proliferation inside cells, and curb the hyperinflammatory state caused by the virus by modulating immune system regulators, minimizing the cytokine storm effect, and modulating the renin-angiotensin system. This chapter discusses the role of curcumin and its derivatives in the prevention and treatment of COVID-19 infection, considering the molecular mechanisms involved. It will also focus on the molecular and cellular profiling techniques as essential tools in this research, as these can be used in the identification and development of new biomarkers, drug targets, and therapeutic approaches for improved patient care.

Psychological Distress Impact of Coronavirus Disease (COVID-19) Outbreak on Three Continents: A Systematic Review and Meta-analysis.

BACKGROUND: The dire state of coronavirus disease (COVID-19) outbreak has had a substantial psychological impact on society. METHODS: A systematic search was performed through Medline, PubMed, Embase, Scopus, and Web of Science, to investigate the impact of the COVID-19 pandemic on the psychological health of individuals in various countries. Subgroup analyses considered gender and classification of countries into three continents of America, Europe, and Asia. Only studies that used the COVID-19 Peritraumatic Distress Index (CPDI) questionnaire as a tool to assess mental distress were included in this meta-analysis. Heterogeneity among studies was assessed by I2 statistic, and the random-effects model was utilized to obtain the pooled prevalence. RESULTS: This pooled analysis included a large data sample of 21 studies consisting of 94,414 participants. The pooled prevalence of the psychological distress during the time of COVID-19 pandemic by CPDI for the continent of Asia was 43% (34.6% mild-to-moderate and 8.4% severe) which was greater than that for Europe (35%; 30% mild-to-moderate and 5% severe) but lower than that for America (64.3%; 45.8% mild to moderate and 18.5% severe). In addition, the prevalence of psychological distress according to CPDI was higher in females (48%; 40% mild to moderate, 13% severe) compared with males (59%; 36% mild to moderate and 5% severe). CONCLUSIONS: Our findings suggest that psychological distress in the Americas is a larger problem than in Asia and European continents. Females appear to be more vulnerable and may therefore require further attention in terms of preventive and management strategies. Implementation of both digital and molecular biomarkers is encouraged to increase objectivity and accuracy of assessing the dynamic changes in mental health in the current and future pandemics.

A Molecular Biomarker-Based Triage Approach for Targeted Treatment of Post-COVID-19 Syndrome Patients with Persistent Neurological or Neuropsychiatric Symptoms.

Approximately 30% of COVID-19 cases may experience chronic symptoms, known as post-COVID-19 syndrome (PCS). Common PCS symptoms can include fatigue, cognitive impairment, and persistent physical, neurological, and neuropsychiatric complaints. To improve healthcare and management of the current and future pandemics, we highlight the need for establishing interdisciplinary post-viral outpatient clinics comprised of specialists in fields such as psychiatry, psychotherapy, neurology, cardiology, pneumology, and immunology. In this way, PCS patients with a high health burden can receive modern diagnostics and targeted therapeutic recommendations. A key objective is to distinguish the "sick recovered" from the "healthy recovered." Our hypothesis is that there is a PCS subgroup with autoimmune-mediated systemic and brain-vascular dysregulation, which may lead to circulatory disorders, fatigue, cognitive impairment, depression, and anxiety. This can be clarified using a combination of specific antibody diagnostics and precise clinical, psychological, and apparative testing.

The Potential Effect of Royal Jelly on Biomarkers Related to COVID-19 Infection and Severe Progression.

Royal jelly is a yellowish to white gel-like substance that is known as a "superfood" and consumed by queen bees. There are certain compounds in royal jelly considered to have health-promoting properties, including 10-hydroxy-2-decenoic acid and major royal jelly proteins. Royal jelly has beneficial effects on some disorders such as cardiovascular disease, dyslipidemia, multiple sclerosis, and diabetes. Antiviral, anti-inflammatory, antibacterial, antitumor, and immunomodulatory properties have been ascribed to this substance. This chapter describes the effects of royal jelly on COVID-19 disease.

Predicting the COVID-19 Patients Status Using Chest CT Scan Findings: A Risk Assessment Model Based on Decision Tree Analysis.

BACKGROUND: The role of chest computed tomography (CT) to diagnose coronavirus disease 2019 (COVID-19) is still an open field to be explored. The aim of this study was to apply the decision tree (DT) model to predict critical or non-critical status of patients infected with COVID-19 based on available information on non-contrast CT scans. METHODS: This retrospective study was performed on patients with COVID-19 who underwent chest CT scans. Medical records of 1078 patients with COVID-19 were evaluated. The classification and regression tree (CART) of decision tree model and k-fold cross-validation were used to predict the status of patients using sensitivity, specificity, and area under the curve (AUC) assessments. RESULTS: The subjects comprised of 169 critical cases and 909 non-critical cases. The bilateral distribution and multifocal lung involvement were 165 (97.6%) and 766 (84.3%) in critical patients, respectively. According to the DT model, total opacity score, age, lesion types, and gender were statistically significant predictors for critical outcomes. Moreover, the results showed that the accuracy, sensitivity and specificity of the DT model were 93.3%, 72.8%, and 97.1%, respectively. CONCLUSIONS: The presented algorithm demonstrates the factors affecting health conditions in COVID-19 disease patients. This model has the potential characteristics for clinical applications and can identify high-risk subpopulations that need specific prevention. Further developments including integration of blood biomarkers are underway to increase the performance of the model.

Statins: Beneficial Effects in Treatment of COVID-19.

The recent viral disease COVID-19 has attracted much attention. The disease is caused by SARS-CoV-19 virus which has different variants and mutations. The mortality rate of SARS-CoV-19 is high and efforts to establish proper therapeutic solutions are still ongoing. Inflammation plays a substantial part in the pathogenesis of this disease causing mainly lung tissue destruction and eventually death. Therefore, anti-inflammatory drugs or treatments that can inhibit inflammation are important options. Various inflammatory pathways such as nuclear factor Kappa B (NF-κB), signal transducer of activators of transcription (STAT), nod-like receptor family protein 3 (NLRP), toll-like receptors (TLRs), mitogen-activated protein kinase (MAPK), and mammalian target of rapamycin (mTOR) pathways and mediators, such as interleukin (IL)-6, IL-1ß, tumor necrosis factor-α (TNF-α), and interferon-γ (INF-γ), cause cell apoptosis, reduce respiratory capacity and oxygen supply, eventually inducing respiratory system failure and death. Statins are well known for controlling hypercholesterolemia and may serve to treat COVID-19 due to their pleiotropic effects among which are anti-inflammatory in nature. In this chapter, the anti-inflammatory effects of statins and their possible beneficial effects in COVID-19 treatment are discussed. Data were collected from experimental and clinical studies in English (1998-October 2022) from Google Scholar, PubMed, Scopus, and the Cochrane Library.

The effect of caloric restriction and fasting on cancer.

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.

Changes in leukocytes and CRP in different stages of major depression.

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 < 0.001, RMD: 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.

Molecular mimicry of NMDA receptors may contribute to neuropsychiatric symptoms in severe COVID-19 cases.

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.

New Therapeutic Approaches and Biomarkers for Increased Healthspan.

Healthcare costs have increased in developing countries over the last few decades, mostly due to the escalation in average life expectancy and the concomitant increase in age-related disorders. To address this issue, widespread research is now being undertaken across the globe with the aim of finding a way of increasing healthy aging. A number of potential interventions have already shown promise, including lifestyle changes and the use of natural products or pharmaceuticals that may delay the onset of diseases associated with the aging process. In parallel, a number of potential biomarkers have already been identified that can be used for assessing risk of developing age-associated disorders and for monitoring response to therapeutic interventions. This review describes the most recent advances towards the goal of achieving healthier aging with fewer disabilities that may lead to enhanced quality of life and reduced healthcare costs around the world.

Research in the Middle East into the Health Benefits of Curcumin.

The Middle East is known as the cradle of civilization. It was the crossroads of ancient empires and the birthplace of major world religions. Today, it is the center of many world issues due to economic, religious, and political reasons. Although it has lagged behind many other regions of the world in medicinal research, this has increased dramatically in recent years with increasing numbers of relevant publications. Much of this research has focused on increasing our understanding of the aging process and attempting to identify biomarkers and natural products to improve the human health span. This review provides a brief overview of the research conducted in the Middle East on the health benefits of curcumin, a phytochemical derived from the famous spice turmeric. These efforts have been mainly spearheaded by Iran.