**1. Introduction**

In the last years, novel and effective immunotherapies for patients with different tumor types are becoming clinically important, because of the remarkable clinical efficacy observed with several immune checkpoint inhibitors such as cytotoxic T lymphocyte antigen 4 (CTLA-4) and the programed death receptor 1 (PD-1) or its ligand (PD-L1) [1–12]. Whereas anti-CTLA-4 antibodies (ipilimumab and tremelimumab), anti-PD-1 antibodies (nivolumab and pembrolizumab), and anti-PD-L1 antibodies (atezolizumab, avelumab, and durvalumab) have produced remarkable results, increasing the survival prognosis in many cancer types, it is still unknown why some tumors do not respond to or relapse after this type of treatment. In this way, increased observations suggest that tumors rich in tumor-associated immune cells (TAICs) may respond to therapies targeting immune system inhibitory or stimulatory mechanisms, and tumors with non-TAICs may require additional interventions aimed at promoting optimal inflammation and innate immune activation in the tumor microenvironment [13–15]. Indeed, characterization of different immune checkpoints as well as tumor microenvironment in patients with cancer has become

a fundamental step in providing evidence for the presence of distinct immunologic phenotypes, based on the presence or absence of various immune cells [1, 16, 17] that can predict the response to the therapy. In this way, the study of immune checkpoints and TAICs and their interaction prompt the need for multiplexed analyses of tumor tissues. To address this need, in the last years, multiplex imaging platforms have emerged as an important tool to provide critical information about cancer microenvironment, prognosis, therapy, and relapse [18–22]. Different components in the tumor microenvironment can be examined simultaneously using multiplex methodologies, providing insight into biological cross-talk present at the tumor-host interface and from subcellular levels to entered cell populations. In addition, the precision of these new techniques can be used to evaluate the special distribution of multiple biomarkers detected simultaneously, and their coexpressions or interactions between cells are becoming a essential tool to study tumor tissues [22] and to ultimately enhance disease diagnosis and better inform timely patient care [23].

Multiplex technologies are being used to identify the presence of multiple biological markers as immune checkpoint and TAICs on a single tissue sample [24]. The multiplex imagining techniques provide unique biological information that in many cases cannot be obtained by other imaging methods or by single immunohistochemistry (IHC) techniques. As mentioned, individual cells can be accessed with extraordinary fidelity equal to that achievable in the bulk population, such that even rare cell populations can be studied to understand their important role in translational research, and this knowledge can be applied in cancer prevention and treatment. In this chapter, we will discuss one of the most reliable and a very well-known methodology to identify simultaneous biomarkers in formalin-fixed, paraffin-embedded (FFPE) specimens as well as its imaging analysis platform as an important tool for potential application in future cancer immunotherapy biomarker discoveries.


*6.2.1 Biofertilizer (*X. autotrophicus*) for bioremediation of environment polluted by chemical agents*

In that sense EPGPB (likes PGPM or/and PGPR can be classified as biofertilizers when they sustainable options to plant nourishment and enrichment source that would useful for bioremediation and/or phytoremediation (double actions plants and biofertilizer) for soil contaminated by chemical agents [87, 88]. There for *X. autotrophicus* is has been applied in bioaugmentation trials for cleaning up any environmental impacted by chemical agents [86] which due to powerful genetic capacity is able to degradate a wide range of chemical agents under several environmental conditions either soil and or water in that sense it been reported that *X. autotrophicus* is able to biodegradate of 1,2- dichloroethane (DCE) one of the largest Xanthobacter autotrophicus *an Endophytic Beneficial Bacterium for Wheat and Other Plants… DOI: http://dx.doi.org/10.5772/intechopen.102066*

chlorinated industrial chemical, most of it being used for synthesis of vinyl chloride and smaller amounts for ethylene diamine and other chemicals. It was also used as a solvent. Groundwater contamination is mainly due to leakages and improper waste disposal. *X. autotrophicus* can attack DCE by using some specific enzimes under oxic conditions was investigated in the 1980s [89, 90] required for prolonged groundwater bioremediation polluted by DCE. Such systems are operated under non-sterile conditions, and long-term survival of enzymes would require separate enzyme production and a process allowing for physical separation of the biocatalyst from groundwater. There may be attractive application opportunities if biotransformation of synthetic chemicals in waste streams leads to products that can be recycled, e.g., when a wastewater product can cleaning up. This issue that received attention during the development of strains of *X. autotrophicus* growing on 1,2,3-trichloropropane (TCP) and another xenobiotic compound that polluted wastewater [86, 90–92].

A bioformulation is not effective until it does not have an impact in field conditions, market existence and reliability and cost effectiveness [93]. Production of bioformulation is not only dependent on the detailed knowledge of microbial as well as plant physiology, but a number of technological challenges are also involved such as fermentation process, formulation type, population of microbe, and delivery systems [94]. Barea [59] has published that in order to get better bioformulation for any domestic crops is important to understand the interaction among EPGPB or PGPM. To reproduce those microorganisms is important the chemical composition of broth media as well as the main and best conditions for each microorganisms need to get enough amount of them for bioformulation applying in open agriculture [95]. Including legal and ecological permission for safe crops production. A key quality of any bioformulation has to be water soluble to make sure a positive effect on any domestic crop Himel et al. [96] and Bateman [97] underline for those bioformulation which are applying in in aerosol based on a droplet size that is sufficient to inoculate seeds and plants with excellent results. For bioformulations applied foliarly, it is important to consider all environmental factors: solar radiation, high temperatures, ultraviolet light, etc. that limit the survival of beneficial plant microorganisms [98]. In this sense, the type of bioformulations must be appropriate to the form and vehicle that transport the beneficial plant microorganisms according to the recommended application directly to the soil, to the seeds or plants so that the forecast of the result favors agricultural production or control of some disease or pest [99]. Therefore, it is important research for the innovation of bioformulation suitable for agricultural crops [58] that comply with the quality and legality standards to satisfy the world market demand for safe food without risk of environmental damage [100]. A fundamental aspect for the world market of biological inoculants has been the necessary implementation of microbiological quality controls with reliable protocols that are endorsed by laws in the world that protect those farmers who, when applying them, have the confidence that they will have positive results in production. agriculture, due in part to the unfortunate experience of bioformulations without microbiological or legal quality that have caused a rejection of some sectors involved in sustainable agricultural production, an aspect that has not yet been resolved in the world [68]. In an integral sense that the biotechnology of the formulation of inoculants requires solid research for the best selection of microorganisms that promote plant growth, as well as the protocols of legal and ethical microbiological quality in the generation of bioformulations that give confidence to be used in the world for a sustainable and harmless agricultural production in harmony with the environment [85].


**5. Conclusion**

The aging mechanism linked to aging is the consequence of multiple heterogeneous processes and is the interplay of several areas including physiological changes, metabolical aging, or cognitive impairment. The HIV-associated aging is distinct from chronological aging and should be treated as well. It will be influenced by the cognitive reserve of the patient, modeled by its social, cultural, physical, and economic environment.


*Review* **Exploitation of Marine-Derived Robust Biological Molecules to Manage Inflammatory Bowel Disease**

**Muhammad Bilal 1,\*, Leonardo Vieira Nunes 2, Marco Thúlio Saviatto Duarte 3, Luiz Fernando Romanholo Ferreira 4,5, Renato Nery Soriano 6 and Hafiz M. N. Iqbal 7,\***

**Abstract:** Naturally occurring biological entities with extractable and tunable structural and functional characteristics, along with therapeutic attributes, are of supreme interest for strengthening the twenty-first-century biomedical settings. Irrespective of ongoing technological and clinical advancement, traditional medicinal practices to address and manage inflammatory bowel disease (IBD) are inefficient and the effect of the administered therapeutic cues is limited. The reasonable immune response or invasion should also be circumvented for successful clinical translation of engineered cues as highly efficient and robust bioactive entities. In this context, research is underway worldwide, and researchers have redirected or regained their interests in valorizing the naturally occurring biological entities/resources, for example, algal biome so-called "treasure of untouched or underexploited sources". Algal biome from the marine environment is an immense source of excellence that has also been demonstrated as a source of bioactive compounds with unique chemical, structural, and functional features. Moreover, the molecular modeling and synthesis of new drugs based on marine-derived therapeutic and biological cues can show greater efficacy and specificity for the therapeutics. Herein, an effort has been made to cover the existing literature gap on the exploitation of naturally occurring biological entities/resources to address and efficiently manage IBD. Following a brief background study, a focus was given to design characteristics, performance evaluation of engineered cues, and point-of-care IBD therapeutics of diverse bioactive compounds from the algal biome. Noteworthy potentialities of marine-derived biologically active compounds have also been spotlighted to underlying the impact role of bio-active elements with the related pathways. The current review is also focused on the applied standpoint and clinical translation of marine-derived bioactive compounds. Furthermore, a detailed overview of clinical applications and future perspectives are also given in this review.

**Keywords:** algal biome; polysaccharides; bioactive entities; engineered cues; therapeutic attributes; inflammatory bowel disease


**Evaluating Meta-Analysis Research of** *Escherichia coli*

Noel Pabalan, Eloisa Singian, Lani Tabangay and Hamdi Jarjanazi

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/67337

### **Abstract**

This chapter summarizes the progress in *Escherichia coli* research that used the meta-analysis approach. Using systematic searches for *E. coli* literature, we tracked meta-analysis publications and analyzed them based on a number of parameters. These included subject/topic (epidemiology, clinical/intervention/prevention and environmental), geographical region (the Americas, Europe and Australasia) and clinical syndrome (enteric, renal, and sepsis/meningitis). These parameters were plotted in terms of time span to obtain a sense of dynamic change or its absence through the years since the turn of the twentieth century. In terms of region, topic and syndrome, highest meta-analysis productivity was attributed to the Americas, clinical/intervention/prevention and enteric, all of which took place in the last 5 years (2011–2016). Over the combined time span of 16 years, the Americas significantly dominated meta-analysis outputs when compared to Europe and Australasia (P = 0.003). In conclusion, our findings facilitate awareness of the progress in this field wherein the studied parameters were analyzed for patterns over time and differential rates of publication productivity.

**Keywords:** *Escherichia coli*, meta-analysis