WHERE PATHOLOGY, MICROBIOLOGY AND VIROLOGY CONVERGE: PROFESSOR VICTOR BABEȘ

"Providential personalities are an essential, unifying, element across cultures, omnipresent in the world’s history [1]. Professor Victor Babeș, a distinguished figure in pathology, microbiology and virology, attended high school in Budapest and pursued his higher medical education in Budapest and Wien. He lectures at the pathology department of the University of Budapest at only 18 years of age. In 1885, he co-authored the first Bacteriology Treaty in Paris alongside Cornil. In 1887, he went on to establish the pathology and bacteriology departments at the Faculty of Medicine, in Bucharest. He contributed to the medical world literature with over 1000 papers, written in different languages. Professor Victor Babeș studied bacteria, viruses, parasites and influenced preventive medicine. Overall, he discovered more than 50 new microbes. An entire book may be devoted just to his pathological discoveries (cancer, leprosy, tuberculosis, diphtheria, actinomycosis, anthrax, syphilis, plague, rabies, etc.). In 1912 he published (in Paris) a vast treaty on rabies; he dedicated 90 of his best works to rabies. Victor Babeș National Institute of Research and Development in Pathology and Biomedical Sciences has been founded on the 28th of April 1887 by Professor Victor Babeș. Initially constituted as a “Bacteriology and Pathology Institute”, it was able to comply with one of the most demanding medical needs of the time and it has contributed to finding realistic solutions regarding medical organization. In terms of importance and activity, the institute represented a prefiguration of the future Ministry of Health [2]. Professor Babeș's life should be remembered for his works that marked the opening of new horizons and for a personality whose genius echoes to this day. "

SEVELAMER CARBONATE MODULATES THE NLRP3 AND NLRP6 INFLAMMASOME EXPRESSION IN PATIENTS WITH DIABETIC NEPHROPATHY

Interaction of microorganisms with the host innate immune system is a crucial factor that could modify diabetes and its associated complications. Recent reports have elucidated the role of NLRP3 inflammasome in diabetes, but to our knowledge there is no data regarding the role of other inflammasomes in diabetes-induced inflammation. To investigate this, blood samples were collected from type 2 diabetes (T2DM) patients with nephropathy as well as from healthy volunteers. After red blood cell lysis, RNA was isolated from all collected blood samples. The expression of NLRP 6, NLRP3, ASC, PRO-IL1Β, and PRO-IL18 was assessed by quantitative Real Time PCR (qRT-PCR). Patients with diabetic nephropathy showed higher NLRP3 inflammasome expression compared to healthy controls whereas no significant differences were observed in case of NLRP6 inflammasome. In addition, Pentraxin 3 expression was elevated in patients with diabetic nephropathy. A detailed analysis of the patient’s clinical data revealed the fact that subjects receiving sevelamer carbonate in their treatment plan harboured low expression of Pentraxin 3 (PTX3) and NLRP3 associated genes.

Molecular Targets and Oxidative Stress Biomarkers in HPV Infection

"Recent research has highlighted the role of oxidative stress in the pathogenesis of HPV-related lesions, especially in neoplastic diseases. Oxidative stress and chronic inflammation are the most important cofactors that HPV requires to persist and induce a malignant process. Data on the role of oxidative stress in benign lesions associated with HPV infection, such as genital and non-genital warts, is scarce and further research is needed. We have determined markers of oxidative stress in the serum of 26 patients with palmoplantar warts and 28 healthy subjects. We have investigated representative markers for the four main molecular targets of oxidative stress, nucleic acids – 8-hydroxy-2’-deoxyguanosine (8-OHdG), lipids – 4-hydroxynonenal (4-HNE), carbohydrates – pentosidine, and proteins – thiol-disulfide homeostasis parameters (TDHP): total thiol (TT), native thiol (NT), and disulfides (DS). The serum levels of oxidative stress markers, 4-HNE, 8-OHdG, and pentosidine, were statistically significantly higher in patients with warts in comparison to the control group (p < 0.01). Regarding TDHP, we have found that TT levels were statistically significantly higher in the patient group compared to the control one (p < 0.05). Even though NT and DS levels were reported to be higher in the patient group compared to the control one, no statistical significance was established (p > 0.05). Our results show enhanced oxidative stress damage in patients with palmoplantar warts and provide valuable data in understanding the molecular mechanisms involved in the pathogenesis of HPV infection. To the best of our knowledge, this is the first study to evaluate both 4-HNE and pentosidine in patients with palmoplantar warts. Keywords: oxidative stress, HPV, warts, thiol-disulfide homeostasis."

MYCOBACTERIUM AVIUM COMPLEX ASSOCIATED IMMUNE RECONSTITUTION INFLAMMATORY SYNDROME IN HIV- INFECTED PATIENT

The incidence of Mycobacterium avium Complex (MAC) Disease in HIV-infected individuals has significantly decreased in recent years due to the introduction of Highly Active Antiretroviral Therapy (HAART) and the initiation of Clarithromycin prophylaxis. We present the case of a patient with advanced AIDS, with generalized lymphadenopathy and digestive symptoms, diagnosed with disseminated MAC, a diagnosis which was based on the results obtained from axillary lymph node and intestinal biopsies. Considering the time of the MAC diagnosis in relation to the recent introduction of antiretroviral (ARV) therapy, we considered immune reconstitution inflammatory syndrome (IRIS) with good evolution under azithromycin, ethambutol and moxifloxacin treatment.

INSIGHTS INTO THE VIRULENCE FACTORS OF ACINETOBACTER BAUMANNII AND THEIR ROLES IN PERSISTENCE AND INFECTIOUS PROCESS

Acinetobacter baumannii is a Gram-negative opportunistic pathogen, which is responsible for a significant and ever-increasing number of health care associated severe infections (such as pneumonia, sepsis, meningitis, wound and urinary tract infections), mainly in severely ill patients. With only a limited number of “traditional” virulence factors, the mechanisms underlying the success of this opportunistic and nosocomial pathogen remain of great interest. With the advent of whole genome sequencing and bioinformatic analysis, some virulence features, including motility, iron-acquisition systems, biofilm development, capsule production, porins, and enzymes, among others have been described. The main purpose of this minireview was to present an update on the main virulence markers of A. baumannii strains and their role in the persistence, infection process and modulation of host immune response.

ANTIBACTERIAL ACTIVITY OF SOME NANO-ANTIMICROBIAL POLY(AMIDOAMINE) (PAMAM) DENDRIMERIC PRODUCTS

"Dendrimers are synthetic, branched macromolecules. Compared to linear polymers, dendrimers hold multiple advantages as potential carrier molecules: high capacity to incorporate pharmacologically active substances, chemical stability of micelles under physiological conditions, increased bioavailability of active substances covalently or noncovalently bound to dendrimers, due to increased dendrimers capacity to cross biological barriers. The carrier potential of dendrimers has been evaluated in combination with different antibiotics, as an alternative way to address the increasing resistance of Gram-positive and Gram-negative bacteria. This paper presents a study on the intrinsic antibacterial properties of the following poly(amidoamino) (PAMAM) ethylenediamine core dendrimers: PAMAM generation 3.5, PAMAM generation 4.0 and PAMAM-OH generation 4.0. The following bacterial strains were used: Staphylococcus aureus ATCC 29213, Staphylococcus aureus ATCC 6538, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 15442, Enterococcus faecalis ATCC 51299 and a multi-drug resistant (MDR) Acinetobacter baumannii clinical isolate. The dendrimers’ concentrations used in the experiment were established within the range of admissibility obtained following cytotoxicity testing on human cell cultures. The dendrimers’ antibacterial activity varied depending on the concentration and the bacterial species. The antibacterial efficacy was quantified by calculating the percentage and logarithmic reduction of the number of viable microorganisms. The logarithmic reduction varied between 0.06 and 1.10, corresponding to percentage reductions between 13% and 92%. The strongest antibacterial activity of all dendrimers used in this study was registered for the D3.5 dendrimer (50 μg/mL) against Acinetobacter baumannii and Pseudomonas aeruginosa ATCC 15442 reference strain. For A. baumannii, a logarithmic reduction of bacterial activity of 1.10 log10 (percentage reduction in the number of CFU of 92%) was registered, while for P. aeruginosa ATCC 15442 the logarithmic reduction was 0.75 log10 (percentage reduction of 82%)."

ADJUVANT AND BENEFICIAL PROBIOTIC THERAPY FOR WOMEN HEALTH

Probiotics are living microbial strains, also considered functional foods, that improve the human intestine and mucosal sites' functionality and normalize the immune system balance. This symbiosis between the human body and microorganisms has attracted scientists and showed a notable role in maintaining human health. The microbiota composition within different sites of the organs can change rapidly and unfavorably, leading to the development of infections or abnormal conditions. The treatments with antibiotics affect and disturb the overall normal microflora, and specifically to the vaginal tract, by inhibiting the spread of the normal microflora of Lactobacillus species. In this sense, probiotics have shown to be an integrative and complementary therapy for the amelioration and prevention of vaginal infections in women. The main objective of the current review is to highlight the importance of probiotics to prevent and treat antibiotic-associated acute and chronic diseases and highlight their possible beneficial impact on women reproductive health. Moreover, the review discusses the recent clinical findings of probiotic therapy concerning protection against vaginal diseases, well-being, infant development, and human body detoxification from the chemical compounds.

MICROEVOLUTION OF DESULFOVIBRIO VULGARIS CO-CULTURED WITH METHANOSARCINA BARKERI REVEALED BY GENOME RE-SEQUENCING AND SINGLE-CELL RT-QPCR ANALYSIS

An integrative approach of adaptive laboratory evolution, whole-genome sequencing and single-cell analysis was used to explore mechanisms related to establishment and maintenance of syntrophic interaction between sulfate-reducing Desulfovibrio vulgaris and methanogen Methanosarcina barkeri. Adaptive laboratory evolution of the D. vulgaris and M. barkeri dual-cultures under two different concentrations of electron donor lactate (38 mM and 50 mM) was conducted by propagating continuously for 50 transfers (~200 generations). Physiological analysis showed that, compared with the initial dual-cultures, the adapted dual-cultures (E38 and E50) have increased growth rates (1.1-fold and 1.2 -fold) and higher biomass yields (3.0-fold and 3.8-fold) on 38 mM and 50 mM lactate, respectively. Whole-genome re-sequencing of D. vulgaris in the adapted dual-cultures revealed 11 and 12 mutations in the D. vulgaris genomes of E38 and E50 dual-cultures, respectively, among which 4 mutations were found in both adapted dual-cultures. RT-qPCR analysis showed that the expression levels of 8 mutated genes were gradually up-regulated in D. vulgaris along with the evolution process. In addition, their heterogeneity was found decreased along with the evolution, as revealed by single-cell RT-qPCR analysis, reflecting adjustments of both gene expression and gene heterogeneity to the gradually established syntrophic relationship.