Gingivitis and periodontitis are induced by numerous pathogenic microbiota hosted in the subgingival biofilm that first trigger the innate immune response. Innate immune response is part of a homeostatic system which is the first line defence and defines the host inherited resistance to infection. Both genetic and environmental factors are involved in variable individual susceptibility to inflammation of periodontal tissues. That is why, although more than 600 bacterial species have been detected in the periodontal plaque, the type of bacteria incriminated in the development of the inflammation is still unclear. Moreover, in the last decade gene polymorphisms have been largely recognised as important conditions associated with increased susceptibility to periodontal diseases. Manipulating the immune response by the development of drugs that inhibit adverse host reactions and promote beneficial effects might be of therapeutic or prophylactic importance. This work intends to assess the importance of Toll-like receptors as main effectors of the innate immune response in the triggering, maintenance and progression of periodontal inflammation, as well as of the involvement of synthetic molecules targeting TLR signalling pathways in treating periodontal diseases.

Tissular hypoxia stimulates vascular morphogenesis. Vascular morphogenesis shapes the cell and, consecutively, tissue growth. The development of new blood vessels is intermediated substantially through the tyrosine kinase pathway. There are several types of receptors inferred to be located in the blood vessel structures. Vascular endothelial growth factor A (VEGF-A) is the leading protagonist of angiogenesis. VEGF-A’s interactions with its receptors VEGFR1, VEGFR2, and VEGFR3, together with disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1), connective tissue growth factor (CTGF), and neuropilin-1 (NRP1), independently, are studied computationally. Peripheral artery disease (PAD), which results in tissue ischemia, is more prevalent in the senior population. Presently, medical curatives used to treat cases of PAD—antiplatelet and antithrombotic agents, statins, antihypertensive remedies with ACE (angiotensin-converting enzyme) impediments, angiotensin receptor blockers (ARB) or β- blockers, blood glucose control, and smoking cessation—are not effective. These curatives were largely established from the treatment of complaint cases of coronary disease. However, these medical curatives do not ameliorate lower limb perfusion in cases of PAD. Likewise, surgical or endovascular procedures may be ineffective in relieving symptoms. Eventually, after successful large vessel revascularization, the residual microvascular circulation may well limit the effectiveness of curatives in cases of PAD. It would thus feel rational to attempt to ameliorate perfusion in PAD by enhancing vascular rejuvenescence and function. Likewise, stimulating specific angiogenesis in these cases (PAD) can ameliorate the patient’s symptomatology. Also, the quality of life of PAD patients can be improved by developing new vasodilative and angiogenetic molecules that stimulate the tyrosine kinase pathway. In this respect, the VEGFA angiogenetic pathway was explored computationally. Docking methodologies, molecular dynamics, and computational molecular design methodologies were used. VEGFA’s interaction with its target was primarily studied. Common motifs in the vascular morphogenesis pathway are suggested using conformational energy and Riemann spaces. The results show that interaction with VEGFR2 and ADAMTS1 is pivotal in the angiogenetic process. Also, the informational content of two VEGFA complexes, VEGFR2 and ADAMTS1, is crucial in the angiogenesis process.

The connection between central obesity and the development and metastasis of various visceral tumors is largely accepted and one of the main causes seems to be the local synthesis of proangiogenic molecules. Progranulin (PRG), recently identified as an adipokine, is a novel pleiotropic growth factor acting on the proliferation and development of fast-growing epithelial cells, cancer cells, and also a proangiogenic factor whose expression is induced in activated endothelial cells. One of the molecules that seems to trigger the angiogenic activity of PRG is vascular endothelial growth factor (VEGF). Two groups of human subjects were considered and adipose tissue was processed for an immunohistochemical and morphometric study after surgery for abdominal tumoral or non-tumoral pathology. The presence of PRG in adipose pads of the omentum was analyzed and its association with VEGF, CD34 and collagen IV in tumoral and non-tumoral visceral pathology was examined. The results showed that PRG but not VEGF expression was upregulated in adipose tissue in tumoral visceral pathology. In conclusion, the involvement of the proangiogenic activity of PRG and VEGF in adipose tissue under tumor conditions may be dependent on the visceral tumor type.

Infections represent a possible risk factor for parkinsonism and Parkinson’s disease (PD) based on information from epidemiology and fundamental science. The risk is unclear for the majority of agents. Moreover, the latency between infection and PD seems to be very varied and often lengthy. In this review, the evidence supporting the potential involvement of infectious microorganisms in the development of Parkinson’s disease is examined. Consequently, it is crucial to determine the cause and give additional treatment accordingly. Infection is an intriguing suggestion regarding the cause of Parkinson’s disease. These findings demonstrate that persistent infection with viral and bacterial microorganisms might be a cause of Parkinson’s disease. As an initiating factor, infection may generate a spectrum of gut microbiota dysbiosis, engagement of glial tissues, neuroinflammation, and alpha-synuclein accumulation, all of which may trigger and worsen the onset in Parkinson’s disease also contribute to its progression. Still uncertain is the primary etiology of PD with infection. The possible pathophysiology of PD infection remains a matter of debate. Furthermore, additional study is required to determine if PD patients develop the disease due to infectious microorganisms or solely since they are more sensitive to infectious causes.

Relapsing polychondritis (RP), falls into the category of rare diseases. The true incidence and prevalence of this rare disease is unknown. The ocular implications in relapsing polychondritis (RP) are numerous and variable, including mainly inflammation in different structures of the eye. As a complication of this inflammatory condition, a closed secondary angle glaucoma has been described. The purpose of our work is to highlight the diversity of ocular determinations of the same rare disease, including different types of glaucoma that may occur under the same circumstances and to make a detailed analysis of chemical therapies based on drug treatment pathways. The paper includes a report of the cases series admitted to the Clinic of Ophthalmology in St. Andrew Emergency Clinical Hospital, Constanta, between 2007 and 2018, cases analyzed and compared with international literature. One of the cases is a 43-year-old male patient with bilateral open-angle bilateral glaucoma. Other cases with RP, are patients of 41 and 46 years old, respectively, presented with unilateral episcleritis. This case series report aims to show that RP can associate even more protean ocular manifestations than already discussed in the literature, with specific chemical therapies and to emphasize the need for team approach and ophthalmological monitoring in the care of RP patients with chemical therapy (drug treatment) for each patient.

Benzoquinolines are used in many drug design projects as starting molecules subject to derivatization. This computational study aims to characterize e benzoquinone drug space to ease future drug design processes based on these molecules. The drug space is composed of all benzoquinones, which are active on topoisomerase II and ATP synthase. Topological, chemical, and bioactivity spaces are explored using computational methodologies based on virtual screening and scaffold hopping and molecular docking, respectively. Topological space is a geometrical space in which the elements composing it can be defined as a set of neighbors (which satisfy a particular axiom). In such space, a chemical space can be defined as the property space spanned by all possible molecules and chemical compounds adhering to a given set of construction principles and boundary conditions. In this chemical space, the potentially pharmacologically active molecules form the bioactivity space. Results show a poly-morphological chemical space that suggests distinct characteristics. The chemical space is correlated with properties such as steric energy, the number of hydrogen bonds, the presence of halogen atoms, and membrane permeability-related properties. Lastly, novel chemical compounds (such as oxadiazole methybenzamide and floro methylcyclohexane diene) with drug-like potential, active on TOPO II and ATP synthase have been identified.