TRAPPC6B biallelic variants cause a neurodevelopmental disorder with TRAPP II and trafficking disruptions.

Highly conserved transport protein particle (TRAPP) complexes regulate subcellular trafficking pathways. Accurate protein trafficking has been increasingly recognized to be critically important for normal development, particularly in the nervous system. Variants in most TRAPP complex subunits have been found to lead to neurodevelopmental disorders with diverse but overlapping phenotypes. We expand on limited prior reports on TRAPPC6B with detailed clinical and neuroradiologic assessments, and studies on mechanisms of disease, and new types of variants. We describe 29 additional patients from 18 independent families with biallelic variants in TRAPPC6B. We identified seven homozygous nonsense (n = 12 patients) and eight canonical splice-site variants (n = 17 patients). In addition, we identified one patient with compound heterozygous splice-site/missense variants with a milder phenotype and one patient with homozygous missense variants. Patients displayed non-progressive microcephaly, global developmental delay/intellectual disability, epilepsy and absent expressive language. Movement disorders including stereotypies, spasticity and dystonia were also observed. Brain imaging revealed reductions in cortex, cerebellum and corpus callosum size with frequent white matter hyperintensity. Volumetric measurements indicated globally diminished volume rather than specific regional losses. We identified a reduced rate of trafficking into the Golgi apparatus and Golgi fragmentation in patient-derived fibroblasts that was rescued by wild-type TRAPPC6B. Molecular studies revealed a weakened interaction between mutant TRAPPC6B (c.454C>T, p.Q152*) and its TRAPP binding partner TRAPPC3. Patient-derived fibroblasts from the TRAPPC6B (c.454C>T, p.Q152*) variant displayed reduced levels of TRAPPC6B as well as other TRAPP II complex-specific members (TRAPPC9 and TRAPPC10). Interestingly, the levels of the TRAPPC6B homologue TRAPPC6A were found to be elevated. Moreover, co-immunoprecipitation experiments showed that TRAPPC6A co-precipitates equally with TRAPP II and TRAPP III, while TRAPPC6B co-precipitates significantly more with TRAPP II, suggesting enrichment of the protein in the TRAPP II complex. This implies that variants in TRAPPC6B may preferentially affect TRAPP II functions compared to TRAPP III functions. Finally, we assessed phenotypes in a Drosophila TRAPPC6B-deficiency model. Neuronal TRAPPC6B knockdown impaired locomotion and led to wing posture defects, supporting a role for TRAPPC6B in neuromotor function. Our findings confirm the association of damaging biallelic TRAPPC6B variants with microcephaly, intellectual disability, language impairments, and epilepsy. A subset of patients also exhibited dystonia and/or spasticity with impaired ambulation. These features overlap with disorders arising from pathogenic variants in other TRAPP subunits, particularly components of the TRAPP II complex. These findings suggest that TRAPPC6B is essential for brain development and function, and TRAPP II complex activity may be particularly relevant for mediating this function.

Evaluating the association between the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet, mental health, and cardio-metabolic risk factors among individuals with obesity.

BACKGROUND: Several previous investigations have examined the brain-protective role of the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet. However, more knowledge is needed about the MIND diet's other favorable impacts. The purpose of this study was to examine the relationship between the MIND diet, mental health, and metabolic markers in individuals with obesity. METHODS: In this cross-sectional study, we included 339 individuals with obesity (BMI ≥ 30 kg/m2) aged 20-50 years. We utilized a semi-quantitative Food Frequency Questionnaire (FFQ), we assessed dietary intake, including 168 food items, and calculated the value of MIND. Metabolic syndrome (MetS) was defined according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) guidelines. We assessed biochemical parameters using Enzymatic methods. Blood pressure and body composition were also determined. RESULTS: Higher tertiles of the MIND diet score were associated with significantly higher energy intake, macronutrients, and brain-healthy food intakes (P < 0.001). Among the brain-unhealthy foods, only the intake of sweets and pastries was significantly lower in the highest versus lowest MIND tertiles. We also observed lower odds of stress (P < 0.05) and higher insulin sensitivity (P < 0.05) in the highest versus lowest MIND diet tertiles. We witnessed no significant changes in other parameters. CONCLUSION: Lower stress levels and higher insulin sensitivity independent of some confounders like age, BMI, sex, and physical activity were associated with the highest tertile of MIND diet score.

Emerging role of human microbiome in cancer development and response to therapy: special focus on intestinal microflora.

In recent years, there has been a greater emphasis on the impact of microbial populations inhabiting the gastrointestinal tract on human health and disease. According to the involvement of microbiota in modulating physiological processes (such as immune system development, vitamins synthesis, pathogen displacement, and nutrient uptake), any alteration in its composition and diversity (i.e., dysbiosis) has been linked to a variety of pathologies, including cancer. In this bidirectional relationship, colonization with various bacterial species is correlated with a reduced or elevated risk of certain cancers. Notably, the gut microflora could potentially play a direct or indirect role in tumor initiation and progression by inducing chronic inflammation and producing toxins and metabolites. Therefore, identifying the bacterial species involved and their mechanism of action could be beneficial in preventing the onset of tumors or controlling their advancement. Likewise, the microbial community affects anti-cancer approaches' therapeutic potential and adverse effects (such as immunotherapy and chemotherapy). Hence, their efficiency should be evaluated in the context of the microbiome, underlining the importance of personalized medicine. In this review, we summarized the evidence revealing the microbiota's involvement in cancer and its mechanism. We also delineated how microbiota could predict colon carcinoma development or response to current treatments to improve clinical outcomes.

Globally Vibrio cholera antibiotics resistance to RNA and DNA effective antibiotics: A systematic review and meta-analysis.

BACKGROUND: Vibrio cholera (V. cholera) is a facultative pathogen that colonizes the small intestine and produces cholerae toxin as the primary virulence factor that causes cholera and fatal diarrhea in humans. In recent decades, V. cholera has emerged as a notorious multidrug-resistant enteric pathogen. This meta-analysis estimated the pooled proportion of V. cholera antimicrobial resistance against RNA and DNA effective antibiotics. METHOD: A systematic search was performed for relevant literature until 05 June 2021 in PubMed, Scopus, Embase, and Web of Science databases. Freeman-Tukey double arcsine transformation was performed to estimate weighted pooled resistance (WPR). RESULTS: The meta-analysis were included 164 articles. The WPR of V. cholera were as follows 76% [67,84] to furazolidone, 65% [29,94] to nitrofurantoin, 55% [44,66] to nalidixic acid, 10% [2,23] to rifampicin, 4%(0, 12) to novobiocin, 4% [2,6] to norfloxacin, 3% [1,4] to ciprofloxacin, 1%(0, 3) to sparofloxacin, 0%(0, 3) to levofloxacin, 0%(0, 2) to ofloxacin, 0%(0, 0) to gatifloxacin. CONCLUSION: V. cholera is a severe problem in Asia and Africa, especially in South Asian countries. The resistance patterns are various in geographical regions. novobiocin 0% (0, 0), and ofloxacin 0% (0, 1) in Africa, gatifloxacin 0% (0, 0), and levofloxacin 0% (0, 6) in Asia and ciprofloxacin 0% (0, 2) in North America are most effective antibiotis. The resistance rate to furazolidone, nalidixic acid, nitrofurantoin, and cephalothin has increased over the years. Monitoring antibiotic resistance and prescribing an appropriate antibiotic is vital to control resistance.

A comprehensive review of chemokine CXC17 (VCC1) in cancer, infection, and inflammation.

A crucial component of the immune system are chemokiness. Chemokine's dysregulation has been linked to a number of pathological diseases. Recently, CXCL17, a chemokine belonging to the CXC subfamily, was identified. With regard to a number of physiological conditions and disorders, CXCL17 either has homeostatic or pathogenic effects. Some research suggests that CXCL17 is an orphan ligand, despite the fact that G protein-coupled receptor (GPR) 35 has been suggested as a possible receptor for CXCL17. Since CXCL17 is primarily secreted by mucosal epithelia, such as those in the digestive and respiratory tracts, under physiological circumstances, this chemokine is referred to as a mucosal chemokine. Macrophages and monocytes are the cells that express GPR35 and hence react to CXCL17. In homeostatic conditions, this chemokine has anti-inflammatory, antibacterial, and chemotactic properties. CXCL17 promotes angiogenesis, metastasis, and cell proliferation in pathologic circumstances like malignancies. However, other studies suggest that CXCL17 may have anti-tumor properties. Additionally, studies have shown that CXCL17 may have a role in conditions such as idiopathic pulmonary fibrosis, multiple sclerosis, asthma, and systemic sclerosis. Additionally, deregulation of CXCL17 in some diseases may serve as a biomarker for diagnosis and prognosis. Clarifying the underlying mechanism of CXCL17's activity in homeostatic and pathological situations may thus increase our understanding of its role and hold promise for the development of novel treatment strategies.

Role of Myeloid-derived suppressor cell (MDSC) in autoimmunity and its potential as a therapeutic target.

Myeloid suppressor cells (MDSCs) are an important class of immune-regulating cells that can suppress T cell function. Most of our knowledge about the function of MDSC comes from studies of cancer models. Recent studies, however, have greatly contributed to the description of MDSC involvement in autoimmune diseases. They are known as a cell population that may negatively affect immune responses by regulating the function of CD4+ and CD8+ cells, which makes them an attractive target for autoimmune diseases therapy. However, many questions about MDSC activation, differentiation, and inhibitory functions remain unanswered. In this study, we have summarized the role of MDSCs in various autoimmune diseases, and the potential of targeting them for therapeutic benefits has been discussed.

Myeloid-derived suppressor cells (MDSCs) in brain cancer: challenges and therapeutic strategies.

The most fatal malignancy of the central nervous system (CNS) is glioblastoma. Brain cancer is a 'cold' tumor because of fewer immunoregulatory cells and more immunosuppressive cells. Due to the cold nature of brain cancers, conventional treatments which are used to manage glioma patients show little effectiveness. Glioma patients even showed resistance to immune checkpoint blockade (ICB) and no significant efficacy. It has been shown that myeloid-derived suppressor cells (MDSCs) account for approximately 30-50% of the tumor mass in glioma. This study aimed to review MDSC function in brain cancer, as well as possible treatments and related challenges. In brain cancer and glioma, several differences in the context of MDSCs have been reported, including disagreements about the MDSC subtype that has the most inhibitory function in the brain, or inhibitory function of regulatory B cells (Bregs). There are also serious challenges in treating glioma patients. In addition to the cold nature of glioma, there are reports of an increase in MDSCs following conventional chemotherapy treatments. As a result, targeting MDSCs in combination with other therapies, such as ICB, is essential, and recent studies with the combination therapy approach have shown promising therapeutic effects in brain cancer.

Giant Primary Epidural Extraskeletal Ewing Sarcoma in Cervical Spine of an Infant: Case Report and Review of the Literature.

Ewing sarcoma (ES) is a highly malignant tumor originating from bones, exceptionally long bones. ES arising from the epidural extramedullary space, primarily the cervical region, is highly unlikely. There have been only six cases of cervical epidural extraskeletal Ewing sarcoma (EEES) in children reported in the literature, all of whom were older than seven years old. Four of seven cases, including the one mentioned in this study, were male (57%). Herein, we report a 1.5-year-old girl who presented with quadriparesis without cognitive impairment and had initially undergone a metabolic disorder evaluation. The spine MRI revealed a mass in the C2-T6 region, and she underwent a biopsy of the tumor via laminectomy. Microscopic examination confirms a diagnosis of ES based on immunohistochemistry. This is the first literature that presents an infant with EEES.

Potential promising anticancer applications of ß-glucans: a review.

ß-Glucans are valuable functional polysaccharides distributed in nature, especially in the cell walls of fungi, yeasts, bacteria, and cereals. The unique features of ß-glucans, such as water solubility, viscosity, molecular weight, and so on, have rendered them to be broadly applied in various food systems as well as in medicine to improve human health. Moreover, inhibition of cancer development could be achieved by an increase in immune system activity via ß-glucans. ß-glucans, which are part of a class of naturally occurring substances known as biological response modifiers (BRMs), have also shown evidence of being anti-tumorogenic, anti-cytotoxic, and anti-mutagenic. These properties make them attractive candidates for use as pharmaceutical health promoters. Along these lines, they could activate particular proteins or receptors, like lactosylceramide (LacCer), Dickin-1, complement receptor 3 (CR3), scavenge receptors (SR), and the toll-like receptor (TLR). This would cause the release of cytokines, which would then activate other antitumor immune cells, like macrophages stimulating neutrophils and monocytes. These cells are biased toward pro-inflammatory cytokine synthesis and phagocytosis enhancing the elicited immunological responses. So, to consider the importance of ß-glucans, the present review introduces the structure characteristics, biological activity, and antitumor functions of fungal ß-glucans, as well as their application.

Lymphopenia associated with survivin and its downstream pathway in COVID-19 serving as a potential route in COVID-19 pathogenesis.

PURPOSE: Starting in 2019, coronavirus disease 2019 (COVID-19) caused an epidemic that was growing rapidly and has harmed millions of people globally. It has been demonstrated that survivin regulates lymphocyte survival, a main route involved in COVID-19 pathogenesis. Survivin belongs to the inhibitor of apoptosis protein (IAP) family, and its primary functions comprise regulating mitosis and inhibiting apoptosis. Since lower survivin expression has been shown to increase the sensitivity of lymphocytes to apoptotic induction, we looked into the function of survivin and its corresponding pathways in COVID-19 pathogenesis. MATERIALS AND METHODS: The expression of survivin, X-linked inhibitor of apoptosis protein (XIAP), caspases 3, 7, 9, and poly (ADP-ribose) polymerase (PARP) was evaluated at both mRNA and protein levels in peripheral blood mononuclear cells (PBMCs) derived from healthy donors and patients with severe and moderate COVID-19 by qRT-PCR and Western blotting, respectively. Then, we enforced apoptosis to COVID-19 patient-derived lymphocytes, and the percent was assessed by flow cytometry. RESULTS: Survivin and XIAP were less expressed in PBMCs derived from COVID-19 patients as apoptosis inhibitors than PARP, cleaved-PARP, caspase 9, and cleaved caspases 3 and 7, according to the results of real-time PCR and Western blot analysis. Additionally, according to the flow cytometry results, the down-regulation of survivin served as a potential factor in the lymphocyte depletion observed in patients with COVID-19. CONCLUSION: The role of survivin and its related pathway was first discovered in the development of COVID-19 and may serve as a potential prognostic and therapeutic target.

The therapeutic effects of mesenchymal stem cell (MSCs) exosomes in covid-19 disease; Focusing on dexamethasone therapy.

The study of diseases, specifically their aetiologies, their step-by-step progressions (pathogenesis), and their impact on normal structure and function, is the focus of pathology, a branch of science and medicine. In therapeutic fields, it is critical to decrease significantly elevated levels of proinflammatory cytokines. The immunomodulatory drugs such as dexamethasone have been used in several of inflammatory diseases such as Covid-19. The use of dexamethasone alone or in combination with other drugs or method such as mesenchymal stem cell (MSC) is one of the most up-to-date discussions about Covid-19. In this review, we first examined the effects of dexamethasone as monotherapy on inflammatory cytokines and then examined studies that used combination therapy of dexamethasone and other drugs such as Baricitinib, Tofacitinib and tocilizumab. Also, therapeutic aspects of MSCs are examined in this review.

A comprehensive review of the role of lncRNAs in gastric cancer (GC) pathogenesis, immune regulation, and their clinical applications.

Gastric cancer (GC) is the fifth most common malignant tumor and the third leading cause of cancer-related deaths worldwide. Although numerous studies have been conducted on advanced GC, the molecular mechanisms behind it remain obscure. Long non-coding RNAs (lncRNAs) are a family of RNA transcripts capable of regulating target genes at transcriptional, post-transcriptional, and translational stages. They do this by modifying mRNAs, miRNAs, and proteins. These RNAs are critical regulators of many biological processes, including gene epigenetics, transcription, and post-transcriptional levels. This article highlights recent results on lncRNAs involved in drug resistance, proliferation, migration, angiogenesis, apoptosis, autophagy, and immune response in GC. The potential clinical implications of lncRNAs as biomarkers and therapeutic targets in GC are also discussed.

Targeting programmed cell death protein 1 (PD-1) for treatment of non-small-cell lung carcinoma (NSCLC); the recent advances.

The immune system uses various immune checkpoint axes to adjust responses, support homeostasis, and deter self-reactivity and autoimmunity. Nevertheless, non-small-cell lung carcinoma (NSCLC) can use protective mechanisms to facilitate immune evasion, which leads to potentiated cancer survival and proliferation. In this light, many blocking anti-bodies have been developed to negatively regulate checkpoint molecules, in particular, programmed cell death protein 1 (PD-1) / PD-ligand 1 (L1), and bypass these immune suppressive mechanisms. Meanwhile, anti-PD-1 anti-bodies such as nivolumab, pembrolizumab, cemiplimab, and sintilimab have shown excellent competence in successfully inspiring immune responses versus NSCLC. Accordingly, the United States Food and Drug Administration (FDA) has recently approved nivolumab (alone or in combination with ipilimumab) and pembrolizumab (alone or in combination with chemotherapy) as first-line treatment for advanced NSCLC patients. However, PD-1 blockade monotherapy remains inefficient in more than 60% of NSCLC patients, and many patients don't respond or acquire resistance to this modality. Also, toxicities related to anti-PD-1 anti-body have been progressively identified in clinical trials and oncology practice. Herein, we will outline the clinical benefits of PD-1 blockade therapy alone or in combination with other treatments (e.g., chemotherapy, radiotherapy, anti-angiogenic therapy) in NSCLC patients. Moreover, we will take a glimpse into the recently identified predictive biomarkers to determine patients most likely to suffer serious adverse events to decrease untoward toxicity risk and diminish treatment costs.

Recent advances in pre-conditioned mesenchymal stem/stromal cell (MSCs) therapy in organ failure; a comprehensive review of preclinical studies.

Mesenchymal stem/stromal cells (MSCs)-based therapy brings the reassuring capability to regenerative medicine through their self-renewal and multilineage potency. Also, they secret a diversity of mediators, which are complicated in moderation of deregulated immune responses, and yielding angiogenesis in vivo. Nonetheless, MSCs may lose biological performance after procurement and prolonged expansion in vitro. Also, following transplantation and migration to target tissue, they encounter a harsh milieu accompanied by death signals because of the lack of proper tensegrity structure between the cells and matrix. Accordingly, pre-conditioning of MSCs is strongly suggested to upgrade their performances in vivo, leading to more favored transplantation efficacy in regenerative medicine. Indeed, MSCs ex vivo pre-conditioning by hypoxia, inflammatory stimulus, or other factors/conditions may stimulate their survival, proliferation, migration, exosome secretion, and pro-angiogenic and anti-inflammatory characteristics in vivo. In this review, we deliver an overview of the pre-conditioning methods that are considered a strategy for improving the therapeutic efficacy of MSCs in organ failures, in particular, renal, heart, lung, and liver.

A review of the effect of COVID-19 on immune responses of the body.

After the world faced the epidemic of COVID-19 caused by the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), novel clinical evidence and genetics related to this virus are emerging. This virus presents a broad range of clinical manifestations that mainly include various asymptomatic infections and severe pneumonia that are followed by multiple organ failures which could lead to death. The immune system has a critical role in the protection of the body against viruses and diseases and the production of antibodies against pathogens. The present study aimed to investigate the effect of COVID-19 on immune responses of the body. A comprehensive collection of related clinical trials and reviews on the issue of COVID-19 were searched. The main focus of the reviewed studies was on immune response in COVID-19. In this regard, various databases of PubMed, EMBASE, Scopus, CINAHL Plus, Cochrane Library, and Google Scholar were reviewed and all related articles from 2010 to 2021 were investigated. All records were searched in the English language and finally records with the highest thematic relevance were included in the main criteria of the study. It is well-known that the immune system's response to the SARS-CoV-2 virus involves all the components of the immune system that are responsible for viral elimination and recovery of the body. However, these immune system responses are involved in the progression of COVID-19 to a severe and lethal process. When the period of COVID-19 in the body increases, the regulation between protective and altered responses will be lost because of exacerbation of the inflammatory components. Therefore, all the responsible factors which affect immunity should be investigated just like that performed in this study.

Screen Time and Body Mass Index Among Children and Adolescents: A Systematic Review and Meta-Analysis.

Background: There is no summative quantitative study that report the difference in BMI in high screen user children and adolescents or give a difference in screen time in children and adolescents with obesity vs. children and adolescents without obesity. In the current meta-analysis we systematically summarized the association between obesity and screen time and meta-analyzed the results. Methods: A systematic search from Scopus, PubMed and Embase electronic databases. Studies that evaluated the association between screen time and obesity up to June 2021. Results: Results revealed that those at the highest screen time category had 0.7 kg/m2 higher BMI (WMD = 0.703; CI = 0.128, 1.278; P < 0.016; I 2 = 95.8%). Moreover, children and adolescents with obesity had a mean value of 0.313 h higher screen time compared with children and adolescents without obesity (WMD: 0.313; OR = 0.219, 0.407; P < 0.001; I 2 = 96%). The results of subgrouping showed that study quality, continent and sample size could reduce the heterogeneity values. No evidence of publication bias was reported according to visual asymmetry of funnel plots and the results of Begg's and Egger's tests. Conclusion: For the first time, the current systematic review and meta-analysis revealed a positive association between screen time and obesity among children and adolescents. Due to the cross-sectional design of the included studies, causal inference is impossible, therefore, further studies in separate analysis of both genders are suggested to better elucidate gender-specific results. Systematic Review Registration: [www.ClinicalTrials.gov], identifier [CRD4202123 3899].

Vitamin D supplementation and cardiac tissue inflammation in obese rats.

OBJECTIVE: The current study was aimed to evaluate the effects of active form of vitamin D on TGF- ß, NF-κB and MCP-1 in heart tissue of obese rats. METHODS: Forty rats were allocated into groups of normal diet and high fat diet for sixteen weeks; then each group was divided into two groups that received either 500 IU/kg vitamin D or placebo for five weeks. Biochemical parameters were assessed by ELISA kits. RESULTS: Vitamin D reduced TGF-ß in obese rats supplemented with vitamin D compared with other groups (P = 0.03). Moreover, vitamin D reduced MCP-1 concentrations in the heart tissues of both vitamin D administered groups compared to placebo one (P = 0.002). NF-κB in the heart of HFD + vitamin D group was significantly lower (P = 0.03). Current study also showed that vitamin D improves glycemic status and reduce insulin resistance significantly in HFD group (P = 0.008). CONCLUSION: Vitamin D was a potential anti- inflammatory mediator of cardiovascular disease and markers of glycemic status in obese rats. Further investigations are needed to better identify the therapeutic role of this vitamin in CVD and to elucidate the underlying mechanisms.

Human Responses in Public Health Emergencies for Infectious Disease Control: An Overview of Controlled Topologies for Biomedical Applications.

COVID-19 originated in Wuhan city of Hubei Province in China in December three years ago. Since then, it has spread to more than 210 countries and territories. This disease is caused by Severe Acute Respiratory Syndrome Coronavirus 2. The virus has a size of one to two nanometers and a single-stranded positive RNA. Droplets spread the virus from coughing and sneezing. This condition causes coughing, fever, acute respiratory problems, and even death. According to the WHO, the virus can survive outside the body for several hours. This research aimed to determine how environmental factors influenced the COVID-19 virus's survival and behavior, as well as its transmission, in a complex environment. Based on the results, virus transmissions are influenced by various human and environmental factors such as population distribution, travel, social behavior, and climate change. Environmental factors have not been adequately examined concerning the transmission of this epidemic. Thus, it is necessary to examine various aspects of prevention and control of this disease, including its effects on climate and other environmental factors.

Clinical characteristics of 200 COVID-19 patients in Mashhad, Iran, February and March 2020.

Introduction: Coronavirus disease 2019 (COVID-19) is a pulmonary involvement which was reported for the first time in December 2019 in the city of Wuhan, Hubei province, China. The aim of the study was to describe the demographic, clinical, laboratory, and radiological characteristics of 204 definitive laboratory-confirmed COVID-19 patients hospitalized in Mashhad, Khorasan Razavi province, Iran. Patients and Methods: This study was performed on 204 laboratory-confirmed COVID-19 patients. A set of laboratory tests combined with various patient information and results from lung high-resolution computed tomography (HRCT) were gathered in a checklist and analyzed to give us a better view of patients who are hospitalized due to the complications caused by this disease. Results: The average age of our patients was 58.83 ± 15.93 years. There were 122 (59.8%) male and 82 (40.2%) female patients, and almost all of our patients had at least one underlying disease. Nine (4.4%) of our patients reported having gone for a trip to COVID-19-epidemic areas in the last 2 weeks. The most common signs shared among all our patients were cough, fever, and decreased O2 saturation; the average respiratory rate was 25.50 ± 6.74/min, average axillary body temperature was 37.69°C ± 0.69°C, and average O2 saturation was 88.34% ± 7.34%. Conclusion: Based on our results, the most common signs of this disease are fever, cough, and shortness of breath, similar to seasonal influenza. Our data on disease severity showed that 33 (16.2%) patients had moderate disease, 139 (68.1%) had severe disease, and 28 (13.7%) were critical; 22 (10.8%) of our hospitalized patients died due to the complications of this disease.

The Role of Atypical Chemokine Receptor D6 (ACKR2) in Physiological and Pathological Conditions; Friend, Foe, or Both?

Chemokines exert crucial roles in inducing immune responses through ligation to their canonical receptors. Besides these receptors, there are other atypical chemokine receptors (ACKR1-4) that can bind to a wide range of chemokines and carry out various functions in the body. ACKR2, due to its ability to bind various CC chemokines, has attracted much attention during the past few years. ACKR2 has been shown to be expressed in different cells, including trophoblasts, myeloid cells, and especially lymphoid endothelial cells. In terms of molecular functions, ACKR2 scavenges various inflammatory chemokines and affects inflammatory microenvironments. In the period of pregnancy and fetal development, ACKR2 plays a pivotal role in maintaining the fetus from inflammatory reactions and inhibiting subsequent abortion. In adults, ACKR2 is thought to be a resolving agent in the body because it scavenges chemokines. This leads to the alleviation of inflammation in different situations, including cardiovascular diseases, autoimmune diseases, neurological disorders, and infections. In cancer, ACKR2 exerts conflicting roles, either tumor-promoting or tumor-suppressing. On the one hand, ACKR2 inhibits the recruitment of tumor-promoting cells and suppresses tumor-promoting inflammation to blockade inflammatory responses that are favorable for tumor growth. In contrast, scavenging chemokines in the tumor microenvironment might lead to disruption in NK cell recruitment to the tumor microenvironment. Other than its involvement in diseases, analyzing the expression of ACKR2 in body fluids and tissues can be used as a biomarker for diseases. In conclusion, this review study has tried to shed more light on the various effects of ACKR2 on different inflammatory conditions.