Supplement Use and Increased Risks of Cancer: Unveiling the Other Side of the Coin.

There is a rising trend in the consumption of dietary supplements, especially among adults, with the purpose of improving health. While marketing campaigns tout the potential health benefits of using dietary supplements, it is critical to evaluate the potential harmful effects associated with these supplements as well. The majority of the scarce research on the potential harmful effects of vitamins focuses on the acute or chronic toxicities associated with the use of dietary supplements. Quality research is still required to further investigate the risks of long-term use of dietary supplements, especially the risk of developing cancers. The present review concentrates on studies that have investigated the association between the risk of developing cancers and associated mortality with the risk of dietary supplements. Such an association has been reported for several vitamins, minerals, and other dietary supplements. Even though several of these studies come with their own shortcomings and critics, they must draw attention to further investigate long-term adverse effects of dietary supplements and advise consumers and healthcare providers to ponder the extensive use of dietary supplements.

Nicotinamide N-methyl transferase and cancer-associated thrombosis: insights to prevention and management.

Nicotinamide metabolism is important in carcinogenesis. Nicotinamide affects the cellular methyl pool, thus affecting DNA and histone methylation and gene expression. Cancer cells have increased expression of nicotinamide N-methyl transferase (NNMT), the key enzyme in nicotinamide metabolism. NNMT contributes to tumor angiogenesis. Overexpression of NNMT is associated with poorer prognosis in cancers. Additionally, NNMT can contribute to cancer-associated morbidities, such as cancer-associated thrombosis. 1-methylnicotinamide (1-MNA), a metabolite of nicotinamide, has anti-inflammatory and antithrombotic effects. Therefore, targeting NNMT can affect both carcinogenesis and cancer-associated morbidities. Several antitumor drugs have been shown to inhibit NNMT expression in cancer cells. Implementing these drugs to reverse NNMT effects in addition to 1-MNA supplementation has the potential to prevent cancer-associated thrombosis through various mechanisms.

Body Mass Index as a Predictor of Symptom Duration in COVID-19 Outpatients.

BACKGROUND: Obesity is a risk factor for various diseases and can affect the disease course. Studies have shown detrimental effects of obesity on patients affected with SARS-CoV-2 including increased hospitalization and more severe disease. This study aims to investigate the effects of obesity on symptom duration in patients with COVID-19, and also explore the possibility of using BMI as a predictor of symptom duration in outpatient settings. METHODS: Patients diagnosed with COVID-19 between June and October 2020, who had no other comorbidities, and were planned to receive treatment in the outpatient setting were enrolled in the study. Duration of the symptoms was determined based on participants' self-report of their symptoms. Linear regression was used to create predictive models based on participants' BMI, age, sex, disease presentation, and their self-reported symptom duration. RESULTS: A total of 210 patients were included in the final analysis. Patients with higher BMI had significantly longer symptom duration. Linear regression models showed highest correlation between BMI and symptom duration compared to other covariates. CONCLUSION: Low error in predictions and high coverage of data variability showed BMI can be used as a predictive factor for symptom duration in COVID-19 patients treated in outpatient settings.

Targeting signaling pathways involved in primordial follicle growth or dormancy: potential application in prevention of follicular loss and infertility.

INTRODUCTION: Premature ovarian failure (POF) is one of the important causes of infertility in females. To date, no efficient preventive pharmacological treatment has been offered to prevent POF. Therefore, it is necessary to focus on strategies that provide a normal reproductive lifespan to females at risk of developing POF. AREAS COVERED: Recently, attention has been drawn to discovering pathways involved in primordial follicle activation, as the inhibition of this process might maintain the stock of primordial follicles and therefore, prevent POF. In vitro and animal studies have resulted in the discovery of several of these pathways that can be used to develop new treatments for POF. These studies show crosstalk of these pathways at different levels. One of the important crossing points of many of these pathways involves anti-Mullerian hormone (AMH). Herein, we discuss different aspects of this topic by reviewing related published articles indexed in PubMed and Web of Science as of December 2021. EXPERT OPINION: Although the findings seem promising, most of the studies were conducted on animals, and the interaction between these factors and the possible outcomes of their administration in the long term are still unknown. Therefore, further investigation is necessary to assess these aspects.

Case Report of a Novel NFkB Mutation in a Lymphoproliferative Disorder Patient.

BACKGROUND: Lymphoproliferative disorders include a heterogeneous list of conditions that commonly involve dysregulation of lymphocyte proliferation resulting in lymphadenopathy and bone marrow infiltration. These disorders have various presentations, most notably autoimmune manifestations, organomegaly, lymphadenopathy, dysgammaglobulinemia, and increased risk of chronic infections. CASE PRESENTATION: A young boy presented with symptoms overlapping different lymphoproliferative disorders, including episodes of chronic respiratory tract infections, dysgammaglobulinemia, lymphadenopathy-associated with splenomegaly as well as skin rashes. Genetic studies revealed multiple heterozygous variants, including a novel mutation in the NFκB1 gene. CONCLUSION: This novel mutation can reveal new aspects in the pathogenesis of lymphoproliferative disorders and propose new treatments for them.

Adherence of the General Public to Self-Protection Guidelines During the COVID-19 Pandemic.

OBJECTIVE: The coronavirus disease (COVID-19) pandemic is rapidly growing due to a high level of contagiousness. Different measures have been taken to slow the spread of the virus. Appropriate use of personal protective equipment (PPE) is one of these key measures. In this cross-sectional study, we investigated adherence of the general public to use of PPE and their knowledge regarding the rationale behind their use. METHODS: Two samples were chosen from public places (a subway station and a city store) in Tehran, Iran, one of the countries affected by COVID-19. Individuals were observed for appropriate use of PPE and interviewed regarding their knowledge on some basic self-protection information. RESULTS: Approximately half of the 431 participants did not take any measures to ensure hand hygiene, whereas those who did not use respiratory protection were far fewer. A considerable number of individuals, however, did not use these PPE correctly. On the other hand, there was a gap in the knowledge of the general public regarding different aspects of protective measures. The majority of the participants were receptive toward education on preventive measurements through public media. CONCLUSION: Education is an important aspect in containing the COVID-19 pandemic, as it directly increases adherence of the general public to protective measures.

The role of noncoding RNAs in pituitary adenoma.

Pituitary adenomas (PAs) are common cranial tumors that affect the quality of life in patients. Early detection of PA is beneficial for avoiding clinical complications of this disease and increasing the quality of life. Noncoding RNAs, including long noncoding RNA, miRNA and circRNA, regulate protein expression, mostly by inhibiting the translation process. Studies have shown that dysregulation of noncoding RNAs is associated with PA. Hence understanding the expression pattern of noncoding RNAs can be considered a promising method for developing biomarkers. This article reviews data on the expression pattern of dysregulated noncoding RNAs involved in PA. Possible molecular mechanisms by which the dysregulated noncoding RNA could possibly induce PA are also described.

Lay abstract Pituitary adenomas (PA) are benign, slow-growing tumors of the pituitary gland. The sooner the tumor is diagnosed, the sooner can the patient be treated with medication. The early detection of this disease can reduce the need for surgery to remove the tumor. Noncoding RNAs are small molecules that regulate the functions and behavior of different cells. When the intracellular or extracellular concentration of these small molecules is altered, the functions and behavior of cells and tissues can be affected and changed. Quantifying and analyzing these molecules is a promising tool for the early detection of different diseases, including PA. This article reviews alterations in these small molecules and the relationship between these alterations and the incidence of PA.

Genetic basis of Guillain-Barre syndrome.

Guillain-Barré syndrome (GBS) is an autoimmune disease in which the peripheral nerves are affected. GBS has different subtypes, such as acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor axonal neuropathy (AMAN). Infections, e.g. Campylobacter jejuni, influenza, etc., can lead to GBS. Both environmental and genetic factors play a major role in the occurrence of GBS. Several studies have investigated the genetic basis of GBS. Human leukocyte antigens (HLA) genes, Cluster of Differentiation (CD) 1A, FAS, Fc gamma receptors (FcGR), Intercellular adhesion molecule-1 (ICAM1), different interleukins, Nucleotide oligomerization domain (NOD), Toll-like receptor 4 (TLR4), Tumor necrosis factor-α (TNF-α) are among the genes reported to be involved in susceptibility to the disease. Dysregulation and dysfunction of the mentioned gene products, even though their role in the pathogenesis of GBS is controversial, play a role in inflammatory pathways, regulation of immune cells and system, antigen presentation, axonal degeneration, apoptosis, and cross-reaction. This review aims to summarize associated genes with GBS to contribute to better understanding of GBS pathogenesis and discover the gene pathways that play role in GBS occurrence.

The Epidemiologic Aspects of COVID-19 Outbreak: Spreading Beyond Expectations.

The coronavirus disease 2019 (COVID-19) outbreak started in late 2019 in Wuhan, Hubei Province of China, and quickly spread to the surrounding regions and neighboring countries. A novel coronavirus, the so-called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was found to be responsible for this outbreak potentially originating from pangolins. In China, the outbreak lasted for 1 month until it seemed to be controlled after affecting over 81,000 individuals and causing deaths in over 4200 patients. Subsequently, and after affecting over 118,000 individuals and causing over 4200 deaths, the condition was officially announced as a pandemic by the World Health Organization (WHO). In the meantime, the epidemic curve took a downtrend in China, the original epicenter of the pandemic, but started to rise in other countries with a steep slope. Among over 215 affected countries, the USA, European countries (Italy, Germany, Spain, France, the UK), Iran, and South Korea had the highest frequencies in the matters of infected patients and deaths. Importantly, different countries took different policies when encountered with an outbreak, especially in the matter of accuracy of the report and timing of the action. A part of the delays in reporting was expected, including the lag in the chain of reporting, the shortcomings of tests, missed patients, and inadequate testing facilities. However, there were also political and nontechnical reasons that caused the reporting to be inaccurate. Surveillance seems to be less of a reason for the observed in poor management, and it mostly originated from human decision-making failures and political issues. Besides, the culture of populations and their trust in their governments played an important role on how they reacted to the COVID-19 pandemic and acquired policies. Finally, the characteristics of the world today indicate the danger of probable upcoming outbreaks, and policymakers should utilize the existing opportunities, particularly the advancements in technology and media, to prevent or adequately manage them.

Modification of Glial Cell Activation through Dendritic Cell Vaccination: Promises for Treatment of Neurodegenerative Diseases.

Accumulation of misfolded tau, amyloid ß (Aß), and alpha-synuclein (α-syn) proteins is the fundamental contributor to many neurodegenerative diseases, namely Parkinson's (PD) and AD. Such protein aggregations trigger activation of immune mechanisms in neuronal and glial, mainly M1-type microglia cells, leading to release of pro-inflammatory mediators, and subsequent neuronal dysfunction and apoptosis. Despite the described neurotoxic features for glial cells, recruitment of peripheral leukocytes to the brain and their conversion to neuroprotective M2-type microglia can mitigate neurodegeneration by clearing extracellular protein accumulations or residues. Based on these observations, it was speculated that Dendritic cell (DC)-based vaccination, by making use of DCs as natural adjuvants, could be used for treatment of neurodegenerative disorders. DCs potentiated by disease-specific antigens can also enhance T helper 2 (Th2)-specific immune response and by production of specific antibodies contribute to clearance of intracellular aggregations, as well as enhancing regulatory T cell response. Thus, enhancement of immune response by DC vaccine therapy can potentially augment glial polarization into the neuroprotective phenotype, enhance antibody production, and at the same time balance neuronal cells' repair, renewal, and protection. The characteristic feature of this method of treatment is to maintain the equilibrium in the immune response rather than targeting a single mediator in the disease and their application in other neurodegenerative diseases should be addressed. However, the safety of these methods should be investigated by clinical trials.

Importance of TNF-alpha and its alterations in the development of cancers.

TNF-alpha is involved in many physiologic and pathologic cellular pathways, including cellular proliferation, differentiation, and death, regulation of immunologic reactions to different cells and molecules, local and vascular invasion of neoplasms, and destruction of tumor vasculature. It is obvious that because of integrated functions of TNF-alpha inside different physiologic systems, it cannot be used as a single-agent therapy for neoplasms; however, long-term investigation of its different cellular pathways has led to recognition of a variety of subsequent molecules with more specific interactions, and therefore, might be suitable as prognostic and therapeutic factors for neoplasms. Here, we will review different aspects of the TNF-alpha as a cytokine involved in both physiologic functions of cells and pathologic abnormalities, most importantly, cancers.

Proposing a tandem AND-gate CAR T cell targeting glioblastoma multiforme.

CAR T cell therapy is suggested as an effective method to treat hematological malignancies. However, high recurrence rates and in vivo toxicities have limited their widespread use. In order to reduce toxicity and improve tumor specificity, we propose a CAR T cell targeting glioblastoma multiforme utilizing the synNotch receptor pathway linked to a tandem CAR T cell. The extracellular domain of the synNotch receptor is replaced by a single chain fragment variable specific for the EGF receptor variant III (scfv-EGFRvIII), and covalently bonded to a IL-13Rα2-CD133-tandem CAR. This would produce an AND-gate CAR-T cell, which requires activation of both signals from synNotch receptor binding to EGFRvIII and then binding of the tandem CAR to either of the two IL-13Rα2 or CD133 ligands-specific antigens for glioblastoma stem cells. SynNotch receptor activation along with the 4-1BB costimulatory domain results in CAR T cell expression under the TRE promoter, culminating in a tri-specific and effective tumor stem cell recognition and elimination of glioblastoma multiforme.

State of the art in immunotherapy of neuroblastoma.

Neuroblastoma (NB) is a common and deadly malignancy mostly observed in children. Evolution of therapeutic options for NB led to the addition of immunotherapeutic modalities to the previously recruited chemotherapeutic options. Molecular studies of the NB cells resulted in the discovery of many tumor-associated genes and antigens such as MYCN gene and GD2. MYCN gene and GD2 surface antigen are two of the most practical discoveries regarding immunotherapy of neuroblastoma. The GD2 antigen has been targeted in many animal and human studies including Phase III clinical trials. Even though these antigens have changed the face of pediatric neuroblastoma, they do not take as much credit in immunotherapy of adult-onset neuroblastoma. Monoclonal antibodies have been designed to detect this antigen on the surface of NB tumor cells. Despite bettering the outcomes for NB patients, current therapies still fail in many cases. Studies are underway to discover more specific tumor-associated antigens and more effective treatment options. In the current narrative, immunotherapy of NB - from emerging of this therapeutic backbone in NB to the latest discoveries regarding this malignancy - has been reviewed.