Neurodegeneration is the pathological condition, in which the nervous system or neuron loses its structure, function, or both, leading to progressive degeneration or the death of neurons, and well-defined associations of tissue system, resulting in clinical manifestations. Neuroinflammation has been shown to precede neurodegeneration in several neurodegenerative diseases (NDs). No drug is yet known to delay or treat neurodegeneration. Although the etiology and potential causes of NDs remain widely indefinable, matrix metalloproteinases (MMPs) evidently have a crucial role in the progression of NDs. MMPs, a protein family of zinc (Zn2+)-containing endopeptidases, are pivotal agents that are involved in various biological and pathological processes in the central nervous system (CNS). The current review delineates the several emerging evidence demonstrating the effects of MMPs in the progression of NDs, wherein they regulate several processes, such as (neuro)inflammation, microglial activation, amyloid peptide degradation, blood brain barrier (BBB) disruption, dopaminergic apoptosis, and α-synuclein modulation, leading to neurotoxicity and neuron death. Published papers to date were searched via PubMed, MEDLINE, etc., while using selective keywords highlighted in our manuscript. We also aim to shed a light on pathophysiological effect of MMPs in the CNS and focus our attention on its detrimental and beneficial effects in NDs, with a special focus on Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), Alzheimer’s disease (AD), multiple sclerosis (MS), and Huntington’s disease (HD), and discussed various therapeutic strategies targeting MMPs, which could serve as potential modulators in NDs. Over time, several agents have been developed in order to overcome challenges and open up the possibilities for making selective modulators of MMPs to decipher the multifaceted functions of MMPs in NDs. There is still a greater need to explore them in clinics.

Current therapies for Parkinson’s disease (PD) are palliative, of which the levodopa/carbidopa therapy remains the primary choice but is unable to modulate the progression of neurodegeneration. Due to the complication of such a multifactorial disorder and significant limitations of the therapy, numerous genetic approaches have been proved effective in finding out genes and mechanisms implicated in this disease. Following the observation of a higher frequency of PD in Gaucher’s disease (GD), a lysosomal storage condition, mutations of glycosylceramidase beta (GBA) encoding glucocerebrosidase (GCase) have been shown to be involved and have been explored in the context of PD. GBA mutations are the most common genetic risk factor of PD. Various studies have revealed the relationships between PD and GBA gene mutations, facilitating a better understanding of this disorder. Various hypotheses delineate that the pathological mutations of GBA minimize the enzymatic activity of GCase, which affects the proliferation and clearance of α-synuclein; this affects the lysosomal homeostasis, exacerbating the endoplasmic reticulum stress or encouraging the mitochondrial dysfunction. Identification of the pathological mechanisms underlying the GBA-associated parkinsonism (GBA + PD) advances our understanding of PD. This review based on current literature aims to elucidate various genetic and clinical characteristics correlated with GBA mutations and to identify the numerous pathological processes underlying GBA + PD. We also delineate the therapeutic strategies to interfere with the mutant GCase function for further improvement of the related α-synuclein–GCase crosstalks. Moreover, the various therapeutic approaches such as gene therapy, chaperone proteins, and histone deacetylase inhibitors for the treatment of GBA + PD are discussed.

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Background Before the advent of fibrinolytic therapy as a gold standard method of care for cases of acute ischemic stroke in Romania, issues regarding legal medicine aspects involved in this area of medical expertise were already presented and, in the majority of cases, the doctors seem to be unprepared for these situations. Main text The present research illustrates some of the cases in which these aspects were involved, that adressed a clinical center having 6 years of professional experience in the application of fibrinolytic treatment for stroke. The following cases report either situations in which the afore mentioned therapy was not rightfully administrated or legal aspects regarding the obtainment of informed consent. Conclusion Obtaining informed consent is a mandatory procedure, which takes time, to the detriment of application of fibrinolytic treatment.

Cutaneous melanoma is the most severe skin neoplasia with an increased incidence in the recent decades, particularly due to the intense exposure to sunlight. Our study analyzed the characteristics of malignant melanoma and the role of sentinel node biopsy in the diagnosis and prognosis of the patients with cutaneous melanoma by identifying the regional metastasis. The small or large clusters of circulating cancer cells are expressing epitops identified by some chemical reaction. These reagents are usually monoclonal antibodies with high sensitivity and specificity which are matching with the right receptor from the melanoma cells. The result is an antibody-antigen complex high-light in the microscopic examination by 3,3`-diaminobenzidine (DAB). The study was conducted on a sample of 151 patients diagnosed with melanoma in different developmental stages: 62 had Breslow index between 1-4 mm, 71 patients had Breslow index � 4 mm and 18 patients had Breslow index [ 1 mm. 45 patients (out of 62) with Breslow index between 1-4 mm had SLN positive. The mortality rate was 5% in the case of the patients with SLN positive. Comparing the rate of mortality by considering the Breslow index, 65% of the patients with Breslow index � 4 mm died. The correct identification of the patients with negative sentinel node or positive sentinel node improves staging and can facilitate the subsequent therapeutic decision, which is useful for early identification of the micro metastases and of the patients who require regional complete lymph node dissection.

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Toxoplasmosis is a zoonotic disease caused by the Toxoplasma gondii protozoan parasite. The aim of this study was to determine the frequency of acute toxoplasmosis or its presence in the medical history of 240 pregnant women, depending on age and geographical background. The second purpose was to analyze several medical aspects (clinical and paraclinical) in pregnant women with acute toxoplasmosis. The study identified several serological changes including positive toxoplasma IgM, IgG, and IgA antibodies. The chemiluminescence immunoassay (CLIA) method was used to detect T. gondii-specific IgM and IgG antibodies and the enzyme immunoassay (EIA) method to detect T. gondii-specific IgA antibodies. Of the 96 pregnant women (40%) infected with T. gondii, approximately 1/3 had acquired acute infection and 2/3 had a history of prior acute infection (P<0.0001). No statistically significant differences according to age groups (P= 0.9384) were found in terms of serological profile. The number of patients with negative serology was significantly higher in urban areas than in rural areas (P<0.0001). The highest incidence among the pregnant women with acute toxoplasmosis with a single chain of ganglia affected was represented by those with the involvement of cervical lymph nodes (75%), the difference compared to the involvement of other chains of ganglia being statistically significant (P=0.0087). All 35 pregnant women with acute toxoplasmosis tested positive for T. gondii-specific IgM antibodies. Most pregnant women with acute T. gondii infection (57.1%) tested negative for T. gondii-specific IgM antibody serum titres within 3-6 months of presentation. The difference compared to other intervals from the moment pregnant women sought care was statistically significant (P= 00002). Only 80% of all pregnant women with acute toxoplasmosis tested positive for T. gondii-specific IgA antibodies. Pregnant women with acute toxoplasmosis have a 3.3 times higher risk of pregnancy loss.