Cytokines and their role as immunotherapeutics and vaccine Adjuvants: The emerging concepts.

Cytokines are a protein family comprising interleukins, lymphokines, chemokines, monokines and interferons. They are significant constituents of the immune system, and they act in accordance with specific cytokine inhibiting compounds and receptors for the regulation of immune responses. Cytokine studies have resulted in the establishment of newer therapies which are being utilized for the treatment of several malignant diseases. The advancement of these therapies has occurred from two distinct strategies. The first strategy involves administrating the recombinant and purified cytokines, and the second strategy involves administrating the therapeutics which inhibits harmful effects of endogenous and overexpressed cytokines. Colony stimulating factors and interferons are two exemplary therapeutics of cytokines. An important effect of cytokine receptor antagonist is that they can serve as anti-inflammatory agents by altering the treatments of inflammation disorder, therefore inhibiting the effects of tumour necrosis factor. In this article, we have highlighted the research behind the establishment of cytokines as therapeutics and vaccine adjuvants, their role of immunotolerance, and their limitations.

Multidrug Resistance in Cancer: Understanding Molecular Mechanisms, Immunoprevention and Therapeutic Approaches.

Cancer is one of the leading causes of death worldwide. Several treatments are available for cancer treatment, but many treatment methods are ineffective against multidrug-resistant cancer. Multidrug resistance (MDR) represents a major obstacle to effective therapeutic interventions against cancer. This review describes the known MDR mechanisms in cancer cells and discusses ongoing laboratory approaches and novel therapeutic strategies that aim to inhibit, circumvent, or reverse MDR development in various cancer types. In this review, we discuss both intrinsic and acquired drug resistance, in addition to highlighting hypoxia- and autophagy-mediated drug resistance mechanisms. Several factors, including individual genetic differences, such as mutations, altered epigenetics, enhanced drug efflux, cell death inhibition, and various other molecular and cellular mechanisms, are responsible for the development of resistance against anticancer agents. Drug resistance can also depend on cellular autophagic and hypoxic status. The expression of drug-resistant genes and the regulatory mechanisms that determine drug resistance are also discussed. Methods to circumvent MDR, including immunoprevention, the use of microparticles and nanomedicine might result in better strategies for fighting cancer.

Genomic diversity and molecular dynamics interaction on mutational variances among RB domains of SARS-CoV-2 interplay drug inactivation.

The scientific community has been releasing whole genomic sequences of SARS-CoV-2 to facilitate the investigation of molecular features and evolutionary history. We retrieved 36 genomes of 18 prevalent countries of Asia, Europe and America for genomic diversity and mutational analysis. Besides, we studied mutations in the RBD regions of Spike (S) proteins to analyze the drug efficiency against these mutations. In this research, phylogenenetic analysis, evolutionary modeling, substitution pattern analysis, molecular docking, dynamics simulation, etc. were performed. The genomic sequences showed >99% similarity with the reference sequence of China.TN93 + G was predicted as a best nucleotide substitution model. It was revealed that effective transition from the co-existing SARS genome to the SARS-CoV-2 and a noticeable positive selection in the SARS-CoV-2 genomes occurred. Moreover, three mutations in RBD domain, Val/ Phe367, Val/ Leu 382 and Ala/ Val522, were discovered in the genomes from Netherland, Bangladesh and the USA, respectively. Molecular docking and dynamics study showed RBD with mutation Val/Leu382 had the lowest binding affinity with remdesivir. In conclusion, the SARS-CoV-2 genomes are similar, but multiple degrees of transitions and transversions occurred. The mutations cause a significant conformational change, which are needed to be investigated during drug and vaccine development.

Rodent Ectoparasites in the Middle East: A Systematic Review and Meta-Analysis.

Rodents carry many ectoparasites, such as ticks, lice, fleas, and mites, which have potential public health importance. Middle Eastern countries are hotspots for many emerging and re-emerging infectious diseases, such as plague, leishmaniasis, Crimean Congo hemorrhagic fever, and Q fever, due to their ecological, socioeconomic, and political diversity. Rodent ectoparasites can act as vectors for many of these pathogens. Knowledge of rodent ectoparasites is of prime importance in controlling rodent ectoparasite-borne zoonotic diseases in this region. The current systematic review and meta-analysis performs a comprehensive synthesis of the available knowledge, providing an evidence-based overview of the ectoparasites detected on rodents in Middle Eastern countries. Following a systematic search in Pubmed, Scopus, and Web of Science, a total of 113 published articles on rodent ectoparasites were studied and analyzed. A total of 87 rodent species were documented, from which Mus musculus, Rattus norvegicus, and Rattus rattus were found to be the most common. Fleas were the most reported ectoparasites (87 articles), followed by mites (53), ticks (44), and lice (25). Xenopsylla cheopis, Polyplax spinulosa, Ornithonyssus bacoti, and Hyalomma rhipicephaloides were the most commonly described fleas, lice, mites, and ticks, respectively. Based on the reviewed articles, the median flea, louse, mite, and tick indices were highest in Israel (4.15), Egypt (1.39), Egypt (1.27), and Saudi Arabia (1.17), respectively. Quantitative meta-analysis, using a random-effects model, determined the overall pooled flea prevalence in the Middle East as 40% (95% CI: 25-55, I2 = 100%, p < 0.00001), ranging between 13% (95% CI: 0-30, I2 = 95%, p < 0.00001) in Iran and 59% (95% CI: 42-77, I2 = 75%, p < 0.00001) in Israel. The overall pooled louse prevalence was found to be 30% (95% CI: 13-47, I2 = 100%, p < 0.00001), ranging between 25% in Iran (95% CI: 1-50, I2 = 99%) and 38% in Egypt (95% CI: 7-68, I2 = 100%). In the case of mites, the pooled prevalence in this region was 33% (95% CI: 11-55, I2 = 100%, p < 0.00001), where the country-specific prevalence estimates were 30% in Iran (95% CI: 4-56, I2 = 99%) and 32% in Egypt (95% CI: 0-76, I2 = 100%). For ticks, the overall prevalence was found to be 25% (95% CI: 2-47, I2 = 100%, p < 0.00001), ranging from 16% in Iran (95% CI: 7-25, I2 = 74%) to 42% in Egypt (95% CI: 1-85, I2 = 100%). The control of rodent ectoparasites should be considered to reduce their adverse effects. Using the One Health strategy, rodent control, and precisely control of the most common rodent species, i.e., Mus musculus, Rattus norvegicus, and Rattus rattus, should be considered to control the rodent-borne ectoparasites in this region.

Helminth Parasites among Rodents in the Middle East Countries: A Systematic Review and Meta-Analysis.

Rodents can be a source of zoonotic helminths in the Middle East and also in other parts of the world. The current systematic review aimed to provide baseline data on rodent helminths to recognize the threats of helminth parasites on public health in the Middle East region. Following a systematic search on PubMed, Scopus, and Web of Science, a total of 65 research studies on rodent cestodes, nematodes, and trematodes, which were conducted in the countries of the Middle East, were analyzed. The study identified 44 rodent species from which Mus musculus, Rattus norvegicus, and Rattus rattus were most common (63%) and recognized as the primary rodent hosts for helminth infestation in this region. Cestodes were the most frequently reported (n = 50), followed by nematodes (49), and trematodes (14). The random effect meta-analysis showed that the pooled prevalence of cestode (57.66%, 95%CI: 34.63-80.70, l2% = 85.6, p < 0.001) was higher in Saudi Arabia, followed by nematode (56.24%, 95%CI: 11.40-101.1, l2% = 96.7, p < 0.001) in Turkey, and trematode (15.83%, 95%CI: 6.25-25.1, l2% = 98.5, p < 0.001) in Egypt. According to the overall prevalence estimates of individual studies, nematodes were higher (32.71%, 95%CI: 24.89-40.54, l2% = 98.6, p < 0.001) followed by cestodes (24.88%, 95%CI: 19.99-29.77, l2% = 94.9, p < 0.001) and trematodes (10.17%, 95%CI: 6.7-13.65, l2% = 98.3, p < 0.001) in the rodents of the Middle East countries. The review detected 22 species of helminths, which have zoonotic importance. The most frequent helminths were Capillaria hepatica, Hymenolepis diminuta, Hymenolepis nana, and Cysticercus fasciolaris. There was no report of rodent-helminths from Bahrain, Jordan, Lebanon, Oman, United Arab Emirates, and Yemen. Furthermore, there is an information gap on rodent helminths at the humans-animal interface level in Middle East countries. Through the One Health approach and countrywide detailed studies on rodent-related helminths along with their impact on public health, the rodent control program should be conducted in this region.