Chemokine-cytokine networks in the head and neck tumor microenvironment

Head and neck squamous cell carcinomas (HNSCCs) are aggressive diseases with a dismal patient prognosis. Despite significant advances in treatment modalities, the five-year survival rate in patients with HNSCC has improved marginally and therefore warrants a comprehensive understanding of the HNSCC biology. Alterations in the cellular and non-cellular components of the HNSCC tumor micro-environment (TME) play a critical role in regulating many hallmarks of cancer development including evasion of apoptosis, activation of invasion, metastasis, angiogenesis, response to therapy, immune escape mechanisms, deregulation of energetics, and therefore the development of an overall aggressive HNSCC phenotype. Cytokines and chemokines are small secretory proteins produced by neoplastic or stromal cells, controlling complex and dynamic cell–cell interactions in the TME to regulate many cancer hallmarks. This review summarizes the current understanding of the complex cytokine/chemokine networks in the HNSCC TME, their role in activating diverse signaling pathways and promoting tumor progression, metastasis, and therapeutic resistance development.This study was supported by Ramalingaswami Fellowship (Grant number: D.O.NO.BT/HRD/35/02/2006) from the Department of Biotechnology, Govt. of India, New Delhi to Muzafar A. Macha. Sidra Medicine Precision Program funded this research to Mohammad Haris (5081012001, 5081012001) and Ajaz A. Bhat (5081012003)

Tumor Microenvironment: An Evil Nexus Promoting Aggressive Head and Neck Squamous Cell Carcinoma and Avenue for Targeted Therapy

Head and neck squamous cell carcinoma (HNSCC) is a very aggressive disease with a poor prognosis for advanced-stage tumors. Recent clinical, genomic, and cellular studies have revealed the highly heterogeneous and immunosuppressive nature of HNSCC. Despite significant advances in multimodal therapeutic interventions, failure to cure and recurrence are common and account for most deaths. It is becoming increasingly apparent that tumor microenvironment (TME) plays a critical role in HNSCC tumorigenesis, promotes the evolution of aggressive tumors and resistance to therapy, and thereby adversely affects the prognosis. A complete understanding of the TME factors, together with the highly complex tumor-stromal interactions, can lead to new therapeutic interventions in HNSCC. Interestingly, different molecular and immune landscapes between HPV+ve and HPV-ve (human papillomavirus) HNSCC tumors offer new opportunities for developing individualized, targeted chemoimmunotherapy (CIT) regimen. This review highlights the current understanding of the complexity between HPV+ve and HPV-ve HNSCC TME and various tumor-stromal cross-talk modulating processes, including epithelial-mesenchymal transition (EMT), anoikis resistance, angiogenesis, immune surveillance, metastatic niche, therapeutic resistance, and development of an aggressive tumor phenotype. Furthermore, we summarize the recent developments and the rationale behind CIT strategies and their clinical applications in HPV+ve and HPV-ve HNSCC

Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. Methods: GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. Findings: Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990–2010 time period, with the greatest annualised rate of decline occurring in the 0–9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10–24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10–24 years were also in the top ten in the 25–49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50–74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. Interpretation: As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and developm nt investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens

Circular DNA: How Circular DNA Assists Cancer Roll with Therapeutic Punches

DNA within cells is either present in the form of long strands as in eukaryotes or circular shapes in Yeast plasmids, mitochondrial DNA, and double minutes in tumor cells. Apart from them, ribosomal or telomeric DNA has been found to produce specialized forms of extrachromosomal circular DNA (eccDNA). eccDNA was discovered in both normal and cancer cells in recent times, indicating a much more significant role. The eccDNA has been found to promote tumor proliferation, survival, and aggressiveness in almost half of all cancers by increasing oncogene copy numbers. This chapter will discuss the biogenesis and function of eccDNA and how it promotes tumor adaption under changing microtumour environmental conditions, as in the case of drugs

Excessive Sitting & Cancer Risk in Times of COVID-19 Lockdowns

30-31With much of the time spent inside homes studying, watching TV, reading, or even playing games – all the while sitting – there must be a heavy price to pay

<em>Trichuris</em>: A Critical Review

Trichuris (whipworms) is a type of roundworm that is responsible for trichuriasis in human beings. Globally, 600–800 million people are infected by this helminthic worm per year. Trichuris is more prevalent in some tropical and sub-tropical areas such as East Asia, China, Sub-Saharan Africa, and the Americas. These parasitic nematodes affect the small intestines of mammals, causing a great deal of discomfort. Their life cycle is completed in two stages; mammals and the external environment. The zoonotic transmission of the disease is responsible for huge infections and deaths around the world. In recent times, researchers have gained a lot of understanding about the genetics and parasitology of Trichuris. In this chapter, we will discuss the origin, phylogeny, life cycle, diagnosis, and zoonotic transmission of the parasite. At the same time, the chapter discusses the genomics of the parasite and the future directions that can help us contain this parasitic nematode

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Not AvailableEnvironmental protection has fascinated the attention of the varied section of people globally thereby creating global issue amongst researchers and scientists working in this area. Pesticides are toxic to aquatic biota which form important components of the food chain such as fishes. Fishes are important sources of protein in nation-state’s diet. So a detailed understanding of the pollutant effect on fishes would be rewarding for fish conservation and fishery development. Cypermethrin, a synthetic pyrethroid pesticide and potential toxic pollutant contaminating aquatic ecosystems, was investigated in the present study for acute toxicity. Indian major carp (Cirrhinus mrigala) were selected for the bioassay experiments. Experimental fish were subjected to different concentrations of cypermethrin ranging from 0.40 to 6.40μg/l for 96 hrs in test containers. The static renewal test method of acute toxicity test was used. Water temperature was regulated at 26.8 ± 3° C. In addition, behavioral changes such as loss of schooling behaviour, swimming near the water surface, hyper activity, erratic movements, seizures, loss of buoyancy, darting movements and hitting against the walls of test tanks at each cypermethrin concentration were observed for the individual fish. Data acquired from the cypermethrin acute toxicity tests were evaluated using the arithmetic method of Karber. The 96 hr LC50 value for Cirrhinus mrigala was estimated as 4.57μg/l. The possible variation in the LC 50 values can be attributed to toxicant sensitivity, its concentration and duration of exposure.Indian Council of Agricultural Research (ICAR

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Not AvailableEurycomanone (EN), a quassinoid present in E. longifolia plants acts as a testosterone booster in male animals. The present study was aimed to explore the role of EN in females using fish as model organism. Chitosan nano-conjugated EN nanoparticles were synthesised and tested for their role in reproductive response in female catfish. Three injections of the formulation were given for a period of 21 days and the mRNA expression profile of important genes as well as serum hormones involved in steroid hormone synthesis were evaluated. In gonads, the mRNA expression of genes was upregulated except CYP19a1 (aromatase), that significantly decreased in the treatment groups. The hormone genes, FSH-β and LH-β mRNA levels in brain were upregulated whereas CYP19a2 was sharply downregulated following treatments. The testosterone varied non-significantly while the estradiol-17β serum hormone was significantly diminished. The effect was sustained in chitosan conjugated treatments compared to EN alone. The Gonadosomatic index (GSI) varied non-significantly in different treatments and control. In treatment groups, histological analysis showed the ovarian follicles in the regressed phase. Analysis of the results of the undertaken research leads to conclusion that that EN may not be beneficial for female reproduction due to its obstructive role in estrogenic production.Not Availabl

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Not AvailableThe present study was carried out to investigate the antimicrobial and immunomodulatory activity of Myrica esculenta ethanolic leaf extract (MeALE) in rainbow trout. The juvenile fish were immersed in 20 mg/l (T1) and 40 mg/l (T2) MeALE for 2 and 6 h and then challenged with pathogenic bacteria, A. hydrophila (ATCC 7966, USA) after 6 h post immersion in MeALE. The immuno-haematological parameters and relative percentage survival were recorded over 7 days post-exposure. The amino acid interaction of functional proteins of bacteria with myricetin, the active ingredient of M. esculenta was performed by AutoDock Vina software. FTIR detected the characteristic peak values and revealed the presence of various functional groups, viz. alkenes, amines, alcohols, phenols and aromatic compounds. The MIC of MeALE was found to be 2 mg/ml while MBC was recorded to be 25 mg/ml. Molecular docking revealed a strong affinity between myricetin and functional proteins of the pathogen. The fish immersed in 40 mg/l MeALE showed a significant increase in haematological indices and non-specific immunological parameters. The current study reports the successful use of MeALE as an antimicrobial and immunostimulatory agent in rainbow trout and recommends the dosage of 40 mg/l MeALE for preventing Aeromonas infection.Not Availabl