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Coronary artery disease (CAD) due to atherosclerosis is one of the important reasons for death worldwide. Recent evidence has suggested the essential role of inflammation in the progression of atherosclerosis. Interleukin (IL)-37 is a critical anti-inflammatory member of the IL-1 family which regulates the inflammatory processes. The aim of this study was to compare the serum levels of IL-37 in patients with CAD compared with the control group and its correlation with oxidative stress, cholesterol homeostasis, and inflammation in patients with CAD. A total of 42 patients with CAD and 42 sex-matched and age- matched controls who underwent coronary angiography were included in this study. The serum levels of IL-37 were evaluated via ELISA. Serum levels of biochemical risk factors were determined by enzymatic methods. Serum levels of IL-37 in the CAD group subjects were significantly lower than in the control group and IL-37 was significantly increased in men with CAD than in women with CAD. IL-37 significantly had an inverse correlation with IL-6, tumor necrosis factor-α, IL-32, high-sensitivity C reactive protein, oxidized low-density lipoprotein, and malondialdehyde. Also, IL-37 had a significantly positive correlation with ferric-reducing antioxidant power (FRAP) assay. In addition, IL-37 has positively correlated with ATP-binding cassette transporter A1 and G1 gene expression in peripheral blood mononuclear cells and serum levels of the FRAP. A receiver operating characteristic test displayed that IL-37 level ratios were a relatively significant CAD predictor. Our results indicated that decreased serum levels of IL-37 in patients with CAD and its relationship with inflammatory cytokines and reverse cholesterol transport genes are more likely to be associated in the inflammatory process with disease pathology.

Background: Schizophrenia is a disease of the nervous system, and immune system disorders can affect its pathogenesis. Activation of microglia, proinflammatory cytokines, disruption of the blood-brain barrier due to inflammation, activation of autoreactive B cells, and consequently the production of autoantibodies against system antigens are among the immune processes involved in neurological diseases. Interleukin-32 (IL-32) is a proinflammatory cytokine that is essential in activating innate and adaptive immune responses. This study aimed to measure the serum level of IL-32 as well as the frequency of autoantibody positivity against several nervous system antigens in patients with schizophrenia. Material and Methods: This study was conducted on 40 patients with schizophrenia and 40 healthy individuals in the control group. Serum IL-32 levels were measured by ELISA. The frequency of autoantibodies against Hu, Ri, Yo, Tr, CV2, amphiphysin, SOX1, Zic4, ITPR1, CARP, glutamic acid decarboxylase GAD, recoverin, titin, and ganglioside antigens was measured by the indirect immunofluorescence method. Results: Serum IL-32 levels in patients with schizophrenia were significantly higher compared to the control group. The frequency of autoantibodies against GAD and RI antigens in patients with schizophrenia was significantly higher than in the control group. Autoantibodies were positive in 8 patients for GAD antigen and 5 patients for RI antigen. Autoantibodies were also positive in 2 patients for CV2, 1 patient for Hu, and 1 patient for CARP. Negative results were reported for other antigens. Conclusion: Our findings suggest that elevated the serum IL-32 level and autoantibodies against GAD and RI antigens may be a reflection of immune system dysregulation in patients with schizophrenia.

Bladder cancer (BC) is one of the most prevalent cancers around the world and, if not treated well, has high morbidity and mortality. Many studies have indicated that there may be various roles for the aryl hydrocarbon receptor (AHR) in the immune system. The aim of this study was to determine the frequency of Foxp3(+) regulatory T (Treg) and T helper 17 cells (Th17) in BC tissue in comparison with controls and determine the relationship between AHR, Foxp3(+) Treg and Th17 cells in BC. A total of 40 patients with BC were enrolled in this study. The control group was selected from non‐tumoural parts of bladder tissues from the patients who have undergone cystoscopy. The percentage of regulatory T cells (Foxp3(+)/CD4(+)) and Th17 (IL‐17(+)/CD4(+)), as well as AHR(+) cells in BC tissues and controls, were determined by immunohistochemistry. The results of this study showed that the number of Foxp3(+) Treg and Th17 is significantly higher in bladder tumour tissues in comparison with non‐tumoural tissues. Also, the percentage of AHR(+) lymphocytes and AHR(+) cells was increased significantly in bladder tumour tissues rather than non‐tumoural tissues. This study also found a relation between AHR and Foxp3(+)/CD4(+) T lymphocytes ratio cells in BC. The percentage of Foxp3(+) Tregs and AHR(+) cells were significantly correlated with the grade and stage of BC. An increase in the percentage of Foxp3(+) Treg and Th17 cells may play an important role in tumour immunity; and determining the relationship between AHR and differentiation of Th17/Foxp3(+)Treg in BC can lead to a potential cancer therapeutic possibility.

BackgroundProstate cancer (PCa) is the second most prevalent cancer among men worldwide. This study presents estimates of PCa prevalence, incidence, death, years-of-life-lost (YLLs), years-lived-with-disability (YLDs), disability-adjusted-life-years (DALYs), and the burden attributable to smoking during 1990-2019 in North Africa and Middle East using data of Global Burden of Diseases (GBD) Study 2019.MethodsThis study is a part of GBD 2019. Using vital registration and cancer registry data, the estimates on PCa burden were modeled. Risk factor analysis was performed through the six-step conceptual framework of Comparative Risk Assessment.ResultsThe age-standardized rates (95% UI) of PCa incidence, prevalence, and death in 2019 were 23.7 (18.5-27.9), 161.1 (126.6-187.6), and 11.7 (9.4-13.9) per 100,000 population. While PCa incidence and prevalence increased by 77% and 144% during 1990-2019, respectively, the death rate stagnated. Of the 397% increase in PCa new cases, 234% was due to a rise in the age-specific incidence rate, 79% due to population growth, and 84% due to population aging. The YLLs, YLDs, and DALYs of PCa increased by 2% (-11.8-23.1), 108% (75.5-155.1), and 6% (-8.9-28.1). The death rate and DALYs rate attributable to smoking have decreased 12% and 10%, respectively. The DALYs rate attributable to smoking was 37.4 (15.9-67.8) in Lebanon and 5.9 (2.5-10.6) in Saudi Arabia, which were the highest and lowest in the region, respectively.ConclusionsThe PCa incidence and prevalence rates increased during 1990-2019; however, the death rate stagnated. The increase in the incidence was mostly due to the rise in the age-specific incidence rate, rather than population growth or aging. The burden of PCa attributable to smoking has decreased in the past 30 years.

Adoptive cell immunotherapy with chimeric antigen receptor T (CAR-T) cell has brought a revolutionary means of treatment for aggressive diseases such as hematologic malignancies and solid tumors. Over the last decade, the United States Food and Drug Administration (FDA) approved five types of CAR-T cell therapies for hematologic malignancies, including Idecabtagene vicleucel (Abecma), Lisocabtagene maraleucel (Breyanzi), Brexucabtagene autoleucel (Tecartus), Tisagenlecleucel (Kymriah), and Axicabtagene ciloleucel (Yescarta). Despite outstanding results gained from different clinical trials, CAR-T cell therapy is not free from side effects and toxicities, and needs careful investigations and improvements. Gene-editing technology, clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system, has emerged as a promising tool to address some of the CAR-T therapy hurdles. Using CRISPR/Cas9 technology, CAR expression as well as other cellular pathways can be modified in various ways to enhance CAR-T cells antitumor function and persistence in immunosuppressive tumor microenvironment. CRISPR/Cas9 technology can also be used to decrease CAR-T cell toxicities and side effects. Hereby, we discussed the practical challenges and hurdles related to the accuracy, efficiency, efficacy, safety, and delivery of CRISPR/Cas9 technology to the genetically engineered-T cells. Combining of these two state-of-the-art technologies, CRISPR/Cas9 and CAR-T cells, the field of oncology has an extraordinary opportunity to enter a new era of immunotherapy, which offers novel therapeutic options for different types of tumors.

Prostate cancer (PCa) is one of the most epidemic types of cancer in men. The tumor microenvironment (TME) of PCa is involved in the emergence of immunosuppressive factors such as myeloid-derived suppressor cells (MDSC), which regulate the immune system by several mechanisms, including interleukin (IL)-10 production. On the other hand, IL-17+ helper T cells (Th17) induce MDSCs and chronic inflammation in TME by producing IL-17. This study demonstrated that the frequency of CD33+ pSTAT3+ MDSC and IL-17+ lymphocyte as well as IL-10 messenger RNA (mRNA) expression were significantly higher in the PCa patients than in the benign prostatic hyperplasia (BPH) group. Moreover, there was no significant relationship between the frequency of CD33+ pSTAT3+ MDSC, and IL-17+ lymphocyte with Gleason scores in the PCa group. We suggested that the higher frequency of CD33+ pSTAT3+ MDSC and IL-17+ lymphocyte and the more frequent expression of IL-10 mRNA in PCa patients may play roles in tumor progression from BPH to PCa.

Introduction and purpose Indoleamine 2, 3- dioxygenase (IDO) plays an important role in immunosuppressive pathway, as inhibits responses of T cells and promotes immune tolerance. Host response to Helicobacter pylori (H. pylori) is involved in the infection persistence and it is also associated with different clinical outcomes. The aim of this study was to investigate the role of IDO in H. pylori-infected patients with gastritis diseases and peptic ulcer diseases (PUD) through the assessment of the relationship among IDO protein expression and the numbers of T helper (Th)-1, Th17, Th22, and T regulator (Treg) cells. Materials and methods Antrum biopsy was obtained from H. pylori-negative patients (n = 48) and H. pylori-positive subjects (55 patients with gastritis and 47 patients with PUD), for performing H. pylori status and histopathological assessments. IDO protein expression was evaluated by Western blotting. Results IDO protein expression was significantly higher in gastric biopsies from H. pylori-positive subjects compared to the H. pylori-negative subjects, and also in H. pylori-positive subjects with gastritis disease compared to H. pylori-positive subjects with PUD. Moreover, in H. pylori-positive subjects, a positive correlation was observed between IDO protein expression and the frequency of Treg cells. In addition, a negative correlation was observed between IDO protein expression and the number of Th1, Th17, and Th22. Conclusion Increased IDO protein expression is able to change the number of Th1, Th17, Th22, and Treg cells and these changes are possibly associated with an increase in the risk of PUD development in H. pylori-infected patients.

Background Helicobacter pylori (H. pylori) infection causes inflammation and increases the risk of developing peptic ulcer disease (PUD); however, the exact molecular mechanisms of PUD development remain unclear. The aim of this study was to investigate the expression of CCL18, CCL28, and CXCL13 in H. pylori-positive subjects in comparison with H. pylori-negative subjects, and to determine its association with different clinical outcomes and virulence factors. Methods In total, 55 H. pylori-positive subjects with gastritis, 47 H. pylori-positive subjects with PUD, and 48 H. pylori-negative subjects were enrolled in this study. CCL18, CCL28, and CXCL13 expression were determined using real time polymerase chain reaction (PCR). The virulence factors of H. pylori such as cytotoxin-associated gene A (cagA), outer inflammatory protein A (oipA), blood group antigen-binding adhesin (babA), and vacuolating cytotoxin A (VacA) genes were evaluated using PCR. Results CCL18, CCL28, and CXCL13 expression in H. pylori-positive subjects were significantly higher than H. pylori-negative subjects. CCL18 and CXCL13 expression in H. pylori-positive subjects with oipA+ and babA2+were significantly higher than H. pylori-positive subjects with oipA¯ and babA2¯. CCL18 and CXCL13 expression were found to be significantly elevated in H. pylori-positive subjects with gastritis compared with H. pylori-positive subjects with PUD. CCL28 expression was significantly higher in H. pylori-positive subjects with PUD compared with H. pylori-positive subjects with gastritis. Conclusions The increased of CCL18 and CXCL13 may be involved in the pathogenesis of H. pylori-associated gastritis, while the increased of CCL28 may be involved in the pathogenesis of H. pylori-associated PUD.

In the dark path of tumorigenesis, the more carefully the cancer biology is studied, the more brilliant answers could be given to the countless questions about its orchestrating derivers. The identification of the correlation between Toll‐like receptors (TLRs) and different processes involved in carcinogenesis was one of the single points of blinding light highlighting the interconnection between the immune system and cancer. TLRs are a wide family of single‐pass membrane‐spanning receptors that have developed through the evolution to recognize the structurally conserved molecules derived from microorganisms or damaged cells. But this is not everything about these receptors as they could orchestrate several downstream signalling pathways leading to the formation or suppression of cancer cells. The present review is tempted to provide a concise schematic about the biology and the characters of TLRs and also summarize the major findings of the regulatory role of TLRs and their associated signalling in the pathogenesis of human cancers.

Cardiovascular disease is the leading cause of death globally. Coronary artery disease (CAD) is a chronic inflammatory disease usually caused by atherosclerosis, in which the coronary arteries become narrowed by atheromatous plaque. Plaques in atherosclerosis are formed through the accumulation of lipids and various immune cells. Both adaptive and innate immune systems are involved in the pathogenesis of atherosclerosis and facilitate plaque formation and disease progression. Almost all immune system cells, including neutrophils, B cells, T cells monocytes, macrophages, foam cells, and dendritic cells (DCs), play a vital role in atherosclerotic plaque. Atherogenesis, the normal function of the endothelium, is initially disrupted and, then, cells of the immune system are recruited to the endothelium following increased expression of cell adhesion molecules. Accumulation of immune cells and lipids leads to the formation of a necrotic nucleus. As the disease progresses, smooth muscle cells form fibrous layers, whose rupture results in exposing the necrotic nucleus and thrombosis. Accordingly, the present review was conducted to determine the role of different cells in innate and adaptive immune systems in inhibition and progression of atherosclerosis.

According to the WHO, breast cancer is the most common cancer in women worldwide. Identification of underlying mechanisms in breast cancer progression is the main concerns of researches. The mechanical forces within the tumor microenvironment, in addition to biochemical stimuli such as different growth factors and cytokines, activate signaling cascades, resulting in various changes in cancer cell physiology. Cancer cell proliferation, invasiveness, migration, and, even, resistance to cancer therapeutic agents are changed due to activation of mechanotransduction signaling. The mechanotransduction signaling is frequently dysregulated in breast cancer, indicating its important role in cancer cell features. So far, a variety of experimental investigations have been conducted to determine the main regulators of the mechanotransduction signaling. Currently, the role of miRNAs has been well-defined in the cancer process through advances in molecular-based approaches. miRNAs are small groups of RNAs (∼22 nucleotides) that contribute to various biological events in cells. The central role of miRNAs in the regulation of various mediators involved in the mechanotransduction signaling has been well clarified over the last decade. Unbalanced expression of miRNAs is associated with different pathologic conditions. Overexpression and downregulation of certain miRNAs were found to be along with dysregulation of mechanotransduction signaling effectors. This study aimed to critically review the role of miRNAs in the regulation of mediators involved in the mechanosensing pathways and clarify how the cross-talk between miRNAs and their targets affect the cell behavior and physiology of breast cancer cells.

Background CD19+IL-10+B cells are considered as a particular subset of immunosuppressive cells by producing interleukin 10 (IL-10), which plays an important role in infectious and autoimmune diseases. The aim of this study was to determine the number of CD19+IL-10+B cells in Helicobacter pylori (H. pylori) positive patients in comparison with H. pylori negative patients, and to determine the association with different clinical outcomes, such as gastritis and peptic ulcer disease (PUD), in infected patients. Methods and materials We studied 25 infected patients with gastritis, 25 infected patients with PUD, and 25 patients negative for H. pylori. The number of CD19+IL-10+B cells was determined by immunofluorescence. Results The number of CD19+IL-10+B cells in patients infected with H. pylori was significantly 2.5-fold higher than uninfected patients (P Conclusions These results demonstrate that the increased number of CD19+IL-10+B cells in infected patients and its association with other cells may play an important role in the pathogenesis of H. pylori infection.

Interleukin (IL)-22 is a member of IL-10 family cytokines with various immunologic functions. As its name implies, IL-22 is known to be secreted mainly by Th22 cells, a recently discovered lineage of CD4+ T cells. Also, Th17, Th1, natural killer cells, γδT cells, and innate immune cells along with some nonlymphoid cells have been confirmed as secondary cellular sources of IL-22. Different cell types such as bronchial and intestinal epithelial cells, keratinocytes, hepatocytes, dermal fibroblasts, and tubular epithelial cells are affected by IL-22. Both pathologic and protective roles have been attributed to IL-22 in maintaining gut homeostasis and inflammation. According to the latest fast-growing investigations, IL-22 is significantly involved in various pathologies including allergic diseases, infection, autoimmunity, and cancer development. Regulating gut immune responses, barrier integrity, and inflammation is dependent on a diverse complex of cytokines and mediators which are secreted by mucosal immune cells. Several investigations have been designed to recognize the role of IL-22 in gastrointestinal immunity. This article tries to discuss the latest knowledge on this issue and clarify the potential of IL-22 to be used in the future therapeutic approaches of intestinal disorders including inflammatory bowel diseases and colon cancer.

Exosomes, as natural occurring vesicles, play highly important roles in the behavior and fate of ischemic diseases and different tumors. Secretion, composition, and function of exosomes are remarkably influenced by hypoxia in ischemic diseases and tumor microenvironment. Exosomes secreted from hypoxic cells affect development, growth, angiogenesis, and progression in ischemic diseases and tumors through a variety of signaling pathways. In this review article, we discuss how hypoxia affects the quantity and quality of exosomes, and review the mechanisms by which hypoxic cell-derived exosomes regulate ischemic cell behaviors in both cancerous and noncancerous cells.

Introduction: Aminoglycosides have been long used for antibacterial treatment and are still commonly used in clinical practice. Despite their extensive application and positive effects, drug-related toxicity is considered as the main obstacle for aminoglycosides. Aminoglycosides induce nephrotoxicity through the endocytosis and accumulation of the antibiotics in the epithelial cells of proximal tubule. Most importantly, however, a number of pharmacological agents were demonstrated to have protective activities against nephrotoxicity in experimental animals.Areas covered: In the present systematic review, the authors provide and discuss the mechanisms and epidemiological features of aminoglycoside-induced nephrotoxicity, and focus mainly on recent discoveries and key features of pharmacological interventions. In total, 39 articles were included in this review.Expert opinion: The majority of studies investigated gentamicin-induced nephrotoxicity in animal models. Antioxidants, chemicals, synthetic drugs, hormones, vitamins, and minerals showed potential values to prevent gentamicin-induced nephrotoxicity. Indicators used to evaluate the effectiveness of nephroprotection included antioxidative indexes, inflammatory responses, and apoptotic markers. Among the nephroprotective agents studied, herbs and natural antioxidant agents showed excellent potential to provide a protective strategy against gentamicin-induced nephrotoxicity.

Background: Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. Methods: The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk-outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. Findings: Globally, in 2019, the risk factors included in this analysis accounted for 4·45 million (95% uncertainty interval 4·01-4·94) deaths and 105 million (95·0-116) DALYs for both sexes combined, representing 44·4% (41·3-48·4) of all cancer deaths and 42·0% (39·1-45·6) of all DALYs. There were 2·88 million (2·60-3·18) risk-attributable cancer deaths in males (50·6% [47·8-54·1] of all male cancer deaths) and 1·58 million (1·36-1·84) risk-attributable cancer deaths in females (36·3% [32·5-41·3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20·4% (12·6-28·4) and DALYs by 16·8% (8·8-25·0), with the greatest percentage increase in metabolic risks (34·7% [27·9-42·8] and 33·3% [25·8-42·0]). Interpretation: The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden. We are grateful to the surveillance systems, including cancer registries, that generated and shared observed cancer burden data. S M Aljunid acknowledges the Department of Health Policy and Management, College of Public Health, Kuwait University for the approval and support to participate in this research project. H Ariffin acknowledges support from the Ministry of Higher Education, Malaysia (grant FRGS/1/2021/SKK0/UM/01/1). F Barra acknowledges support from Lega Italiana per la Lotta contro i Tumori - LILT - Bando 5 x 1000 anno 2019. L Belo and M Carvalho acknowledge the support from FCT in the scope of the project UIDP/04378/2020 and UIDB/04378/2020 of UCIBIO and the project LA/P/0140/2020 of i4HB. A J Cohen was supported by the Health Effects Institute, Boston, MA, USA. J Conde acknowledges financial support from the European Research Council - ERC Starting Grant 848325. V M Costa acknowledges her grant (SFRH/BHD/110001/2015), received by Portuguese national funds through Fundação para a Ciência e Tecnologia (FCT), IP, under the Norma Transitória DL57/2016/CP1334/CT0006. T C Ekundayo was supported by the African-German Network of Excellence in Science (AGNES), the Federal Ministry of Education and Research (BMBF) and the Alexander von Humboldt Foundation (AvH). N Ghith acknowledges support from a grant from Novo Nordisk Foundation (NNF16OC0021856). J C Glasbey is support by a Doctoral Research Fellowship from the National Institute of Health Research (NIHR300175). V K Gupta and V B Gupta acknowledge funding support from National Health and Medical Research Council (NHMRC), Australia. C Herteliu, A Pana, and M Ausloos acknowledge partial support by a grant of the Romanian National Authority for Scientific Research and Innovation, CNDS-UEFISCDI, project number PN-III-P4-ID-PCCF-2016-0084. C Herteliu is also partially supported by a grant of the Romanian Ministry of Research Innovation and Digitalization, MCID, project number ID-585-CTR-42-PFE-2021. S Hussain was supported from Operational Programme Research, Development and Education–Project, Postdoc2MUNI (number CZ.02.2. 69/0.0/0.0/18_053/0016952). M Jakovljevic acknowledges partial support through the grant OI 175 014 of the Ministry of Education Science and Technological Development of the Republic of Serbia. J H Kauppila acknowledges research grants from Sigrid Jusélius Foundation and the Finnish Cancer Foundation. M N Khatib acknowledges support from Datta Meghe Institute of Medical Sciences (deemed-to-be-university). Y J Kim was supported by the Research Management Centre, Xiamen University Malaysia [XMUMRF/2020-C6/ITCM/0004]. S L Koulmane Laxminarayana acknowledges institutional assistance by Manipal Academy of Higher Education, Manipal. K Krishan is supported by the UGC Centre of Advanced Study (Phase II), awarded to the Department of Anthropology, Panjab University, Chandigarh, India. I Landires is a member of the Sistema Nacional de Investigación (SNI), which is supported by Panama’s Secretaría Nacional de Ciencia, Tecnología e Innovación (SENACYT). M-C Li was supported by the Ministry of Science and Technology, Taiwan (MOST 110-2314-B-003-001). G Liu acknowledges support from the CREATE Hope scientific fellowship from Lung Foundation Australia. J Liu acknowledges support from the National Natural Science Foundation (72122001). J A Loureiro was supported by Scientific Employment Stimulus (FCT; CEECINST/00049/2018). E Mathews is supported by a Clinical and Public Health Early Career Fellowship (grant number IA/CPHE/17/1/503345) from the DBT India Alliance/Wellcome Trust Department of Biotechnology, India Alliance (2018–2023). T J Meretoja was supported by an unrestricted grant from Cancer Foundation Finland sr. S Mohammed acknowledges a fellowship grant from Alexander von Humboldt Foundation, outside the submitted work. M Molokhia is supported by the National Institute for Health Research Biomedical Research Center at Guy’s and St Thomas’ National Health Service Foundation Trust and King’s College London. L Monasta received support from the Italian Ministry of Health at the Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste - Italy (RC 34/2017). U Mons is supported by the Marga and Walter Boll Foundation, Kerpen, Germany. M A Moosavi acknowledges the financial support of National Institute of Genetics Engineering and Biotechnology (NIGEB). J Musa acknowledges support from the NIH/FICK43TW011416 for research-protected time for cervical cancer research and career development at University of Jos. V Nuñez-Samudio is a member of the Sistema Nacional de Investigación (SNI), which is supported by Panama’s Secretaría Nacional de Ciencia, Tecnología e Innovación (SENACYT). O O Odukoya acknowledges support by the Fogarty International Center of the National Institutes of Health under the award number K43TW010704 for research-protected time. The content is solely the responsibility of all the authors and does not necessarily represent the official views of the National Institutes of Health. A S Oguntade acknowledges funding by a doctoral scholarship from the Nuffield Department of Population Health, University of Oxford (Oxford Population Health). J R Padubidri acknowledges Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal for their constant support in research collaborations. R G Pestell acknowledges support from NIH grant W81XWH1810605 Breast Cancer Research, Breakthrough Grant R21 CA235139-01. Z Z Piracha acknowledges the International Center of Medical Sciences Research (ICMSR), Islamabad (44000), Pakistan. R A Radhakrishnan acknowledges support from Wellcome Trust/DBT India Alliance - IA/CPHI/18/1/503927. U Saeed acknowledges the International Center of Medical Sciences Research (ICMSR), Islamabad, Pakistan. A M Samy acknowledges the support from Ain Shams University and the Egyptian Fulbright Mission Program. F Sha was supported by the Shenzhen Science and Technology Program (grant number KQTD20190929172835662). H R Shahsavari acknowledges the Institute for Advanced Studies in Basic Sciences (IASBS) Research Council. A Shetty acknowledges Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal for all the academic support. D A S Silva acknowledges financing in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brazil (CAPES)—Finance Code 001 and D A S Silva is supported in part by CNPq-Brazil (309589/2021-5). L M L R Silva was supported by project CENTRO-04-3559-FSE-000162, Fundo Social Europeu (FSE). Am Singh is supported by the International Graduate Research Scholarship, University of Tasmania. R Suliankatchi Abdulkader acknowledges support from ICMR—National Institute of Epidemiology. B Unnikrishnan acknowledges Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal. H Xiao acknowledges support from the Public Health Sciences Division of the Fred Hutchinson Cancer Research Center. X Xu is supported by the University of New South Wales (Australia) Scientia Program. C Yu was supported by the National Natural Science Foundation of China (grant number 82173626) and Wuhan Medical Research Program of Joint Fund of Hubei Health Committee (grant number WJ2019H304). Sí

Cervical cancer, caused by human papillomavirus (HPV), is the fourth most common type of cancer among women worldwide. While HPV prophylactic vaccines are available, they have no therapeutic effects and do not clear up existing infections. This study aims to design a therapeutic vaccine against cervical cancer using reverse vaccinology. In this study, the E6 and E7 oncoproteins from HPV16 were chosen as the target antigens for epitope prediction. Cytotoxic T lymphocytes (CTL) and helper T lymphocytes (HTL) epitopes were predicted, and the best epitopes were selected based on antigenicity, allergenicity, and toxicity. The final vaccine construct was composed of the selected epitopes, along with the appropriate adjuvant and linkers. The multi-epitope vaccine was evaluated in terms of physicochemical properties, antigenicity, and allergenicity. The tertiary structure of the vaccine construct was predicted. Furthermore, several analyses were also carried out, including molecular docking, molecular dynamics (MD) simulation, and in silico cloning of the vaccine construct. The results showed that the final proposed vaccine could be considered an effective therapeutic vaccine for HPV; however, in vitro and in vivo experiments are required to validate the efficacy of this vaccine candidate.

Prostate cancer is the second most common cancer and the fifth leading cause of cancer-associated death in men. Previous studies have revealed a surprising ability for an immature population of myeloid cells called myeloid-derived suppressor cells (MDSCs) in the commencement and development of many tumors, including those of prostate cancer. Herein, the molecular and cellular changes of MDSCs in prostate cancer in both human and nonhuman models are reviewed. The suppressive function of MDSCs are also discussed with a particular focus on the role of IL-6 and JAK/STAT3 signaling pathways in the induction of their suppressive activity. Ultimately, a brief review of MDSC-targeting approaches for potential cancer therapy is presented.

Cytotoxic small-molecule drugs have a major influence on the fate of antibody-drug conjugates (ADCs). An ideal cytotoxic agent should be highly potent, remain stable while linked to ADCs, kill the targeted tumor cell upon internalization and release from the ADCs, and maintain its activity in multidrug-resistant tumor cells. Lessons learned from successful and failed experiences in ADC development resulted in remarkable progress in the discovery and development of novel highly potent small molecules. A better understanding of such small-molecule drugs is important for development of effective ADCs. The present review discusses requirements making a payload appropriate for antitumor ADCs and focuses on the main characteristics of commonly-used cytotoxic payloads that showed acceptable results in clinical trials. In addition, the present study represents emerging trends and recent advances of payloads used in ADCs currently under clinical trials.

Background Peptic ulcer disease (PUD) is a common disease worldwide moreover known as stomach ulcer or peptic ulcer. Increased the number of T CD4+ helper cells in response to gastric infection by Helicobacter pylori (H. pylori) play an important role in the development of PUD. The aim of this study was to determine the frequency of T-bet+ cells in H. pylori-infection, its interaction with Th17/Treg cells and its association with the clinical consequences of the infection. Methods A total of 63 patients with PUD, 89 patients with gastritis and 48 H. pylori-negative subjects were enrolled in this study. The number of T-bet+ cells were determined by immunohistochemistry. Results The numbers of T-bet+ cells and INF-γ expression in infected patients were significantly higher than uninfected. Moreover, the number of T-bet+ cells and INF-γ expression in infected patients with PUD were significantly higher than infected patients with gastritis. Additionally, the number of T-bet+ cells and INF-γ expression were found to be inversely correlated with degree of H. pylori density and chronic inflammation score (CIS) in infected patients with gastritis disease, but this correlation was positive in the infected patients with PUD. The number of T-bet+ cells was found to be positively correlated with the number of Th17 cells and inversely correlated with the number of Treg cells in infected patients with gastritis and PUD. Conclusion Abnormal hyper-activation of T-bet+ cells during H. pylori-infection may lead to tissue damage caused by immunopathologic reactions.

Background and study aims Helicobacter pylori (H. pylori) has been implicated in the pathogenesis of most important gastro-duodenal diseases, such as gastritis, peptic ulcer disease (PUD) and gastric cancer. H. pylori upregulates the expression and activity of several matrix metalloproteinases (MMPs) in the gastric mucosa, but the role of MMP-3 and MMP-9 in infected patients with H. pylori have not been clearly defined yet. We examined mucosal MMP-3 and MMP-9 mRNA levels in gastric mucosa of H. pylori infected patients and evaluated the effects of virulence factors cagA and vacA allelic variants on these levels. We also determined correlation between mucosal MMP-3 and MMP-9 mRNA levels and types of disease. Patients and methods Total RNA was extracted from gastric biopsies of 50 H. pylori-infected patients and 50 H. pylori-negative patients. Mucosal MMP-3 and MMP-9 mRNA expression level in H. pylori-infected and non-infected gastric biopsies were determined by real time-polymerase chain reaction (PCR). Presence of vacA (vacuolating cytotoxin A) and cagA (cytotoxin associated gene A) virulence factors were evaluated using PCR. Results The levels of MMP-3 in gastric mucosa were not different between H. pylori-positive and H. pylori-negative patients. There was no correlation between MMP-3 mRNA expression and virulence factor (cagA and vacA allelic variants) and the different types of disease (gastritis and PUD) in infected patients. But MMP-9 mRNA expression was significantly higher in biopsies of H. pylori-infected patients compared to H. pylori-negative patients. Also mucosal MMP-9 mRNA expression in H. pylori-infected patients was significantly associated with cagA status PUD. Conclusion Our results suggest that MMP-9 might be involved in the pathogenesis of H. pylori. PUD could be associated with cag PAI-dependent MMP-9 upregulation.

Prostate cancer (PCa) is one of the most epidemic types of cancer in men. The tumor microenvironment (TME) of PCa is involved in the emergence of immunosuppressive factors such as myeloid-derived suppressor cells (MDSC), which regulate the immune system by several mechanisms, including interleukin (IL)-10 production. On the other hand, IL-17

Coronary Artery Disease (CAD) is a chronic inflammatory disease caused by atherosclerosis and arteries become clogged due to plaque formation, fat accumulation, and various sorts of immune cells. IL-32 is a new proinflammatory cytokine, which enhances inflammation through inducing different inflammatory cytokines. The purpose of current research was to assess IL-32 serum levels in coronary artery disease subjects and its relationship with serum levels of IL-6 and TNF-α. Forty-two subjects diagnosed with CAD and thirty-nine control subjects were enrolled in the research. Serum levels of IL-6, TNF-α, and IL-32 were measured using the enzyme-linked immunosorbent assay (ELISA). IL-32, TNF-α, and IL-6 serum levels were significantly higher by 2.7, 3.48, and 3.2-fold in the CAD subjects than in control subjects, respectively. Moreover, no significant difference was found in TNF-α, IL-6 and IL-32 serum levels with the clogged arteries number in the CAD group. TNF-α and IL-32 serum levels in the CAD subjects with cardiac arterial stenosis in one major vessel were significantly increased than CAD subjects with cardiac arterial stenosis in more than one major vessels. ROC curve analysis revealed that serum levels of IL-32, TNF-α, and IL-6 showed good abilities in predicting CAD. Also, Multiple logistic regression analyses suggested that TNF-α, IL-6, and IL-32, serum levels of LDL and ox-LDL were independently related to the presence of CAD, while HDL serum levels were not. TNF-α, IL-32, and IL-6 showed an increase in CAD group and serum levels of these cytokines showed good abilities in predicting CAD. Our data suggested the involvement of TNF-α and IL-32 in the early stage of CAD.

At the forefront of the battle against pathogens or any endogenously released molecules, toll-like receptors (TLRs) play an important role as the most noble pattern recognition receptors. The ability of these receptors in distinguishing "self" and "non-self" antigens is a cornerstone in the innate immunity system; however, misregulation links inflammatory responses to the development of human cancers. It has been known for some time that aberrant expression and regulation of TLRs not only endows cancer cells an opportunity to escape from the immune system but also supports them through enhancing proliferation and angiogenesis. Over the past decades, cancer research studies have witnessed a number of preclinical and clinical breakthroughs in the field of TLR modulators and some of the agents have exceptionally performed well in advanced clinical trials. In the present review, we have provided a comprehensive review of different TLR agonists and antagonists and discuss their limitations, toxicities, and challenges to outline their future incorporation in cancer treatment strategies.