**5. Conclusions**

Ps affecting the health of numerous individuals worldwide has a multifactorial pathogenesis and recently it was shown that alterations in the skin and intestinal microbiome are involved in the pathogenesis of Ps, therefore microbiome restoration becomes a promising preventive/therapy strategy in this pathology. In our pre-clinical design study, using a mice model of induced psoriatic dermatitis, we have tested the proof-of-concept that IgY raised against pathological human bacteria resistant to antibiotics can alleviate psoriatic lesions and restore immune parameters. We pin-pointed that the IgY specific compound can be a possible pre-biotic alternative adjuvant in Ps. As IgY preparation can be raised against individualized microbiome using this compound can open also the personalized medicine domain in Ps.

**Supplementary Materials:** The following are available online at https://www.mdpi.com/article/ 10.3390/jpm11090841/s1, Table S1: Individual experimental data for erythema (E), skin scaling (S), thickening (T) and PASI score. Table S2: Individual histological parameters for each mouse from groups control, naturally remitted, psoriasis and IgY treated (- represents the absence of the investigated parameter, + low presence; ++ medium presence; +++ intense presence; ++++ extremely high presence).

**Author Contributions:** Conceptualization, M.S., C.C. (Carolina Constantin) and M.N.; methodology, M.S., A.M., G.I., C.C. (Carolina Constantin) and A.I.; writing—original draft preparation, M.S., A.M.; writing—review and editing, C.C. (Constantin Caruntu), M.S. and M.N.; supervision, M.N. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research was funded by Competitiveness Operational Program (COP), IntelBiomed project, SMIS code 105631, ID: P\_40\_197, Grant No. 52/2016, and by Romanian Ministry of Research, Innovation and Digitization, grant PN 19.29.01.01 and PN 19.29.02.03.

**Institutional Review Board Statement:** The study was approved by the Ethics Committee from Victor Babes, Institute (no 88/20 January 2021) and National Sanitary Veterinary and Food Safety Authority (no 598/8 February 2021).

**Informed Consent Statement:** Not applicable.

**Data Availability Statement:** The datasets used and/or analyzed during current study are available from corresponding author on reasonable request.

**Acknowledgments:** Authors would like to thank Emilia Manole (Victor Babes National Institute of Pathology) for the histology of the skin sections. Authors would also like to thank all the technicians from the Animal Husbandry (Victor Babes National Institute of Pathology) for their resilience and patience to follow all the technicalities of this animal model design.

**Conflicts of Interest:** The authors declare no conflict of interest.

#### **Abbreviations**

APC, Allophycocyanin; BD, Becton Dickinson; Bregs, regulatory B cells; CD, Cluster of Differentiation; DC, Dendritic Cell; FACS, Fluorescence-Activated Cell Sorting; FBS, Fetal Bovine Serum; H&E, Haematoxylin-Eosin; FITC, Fluorescein Isothiocyanate; IFN, Interferon; Ig, Immunoglobulin; IL, Interleukin; IMQ, Imiquimod; JAK, Janus Kinase; K2-EDTA, Kalium 2 EthyleneDiamine TetraAcetate; KLRG1, Killer Cell Lectin-Like Receptor G1; NK, Natural Killer cells; PASI, Psoriasis Area Severity Index; PE, Phycoerythrin; PE/Cy, Phycoerythrin Complex with Cyanine; PerCP/Cy, Peridinin Chlorophyll Protein Complex with Cyanine; R, Receptor; RORγt, Retinoic acid receptor-related orphan nuclear receptor gamma t; RPMI, Roswell Park Memorial Institute; SD, Standard Deviation; SW/BW, Spleen Weight/Body Weight; Th, Helper T Cells; TLR, Toll-Like Receptor; TNF, Tumor Necrosis Factor; UV, Ultraviolet.

## **References**


**Corina Daniela Ene 1, \*, Simona Roxana Georgescu 2, \*, Mircea Tampa 3, \*, Clara Matei 4 , Cristina Iulia Mitran 5 , Madalina Irina Mitran 5 , Mircea Nicolae Penescu 1,6 and Ilinca Nicolae 2**


dermatology.mt@gmail.com (M.T.)


**Abstract:** The interaction of reactive oxygen species (ROS) with lipids, proteins, nucleic acids and hydrocarbonates promotes acute and chronic tissue damage, mediates immunomodulation and triggers autoimmunity in systemic lupus erythematous (SLE) patients. The aim of the study was to determine the pathophysiological mechanisms of the oxidative stress-related damage and molecular mechanisms to counteract oxidative stimuli in lupus nephritis. Our study included 38 SLE patients with lupus nephritis (LN group), 44 SLE patients without renal impairment (non-LN group) and 40 healthy volunteers as control group. In the present paper, we evaluated serum lipid peroxidation, DNA oxidation, oxidized proteins, carbohydrate oxidation, and endogenous protective systems. We detected defective DNA repair mechanisms via 8-oxoguanine-DNA-glycosylase (OGG1), the reduced regulatory effect of soluble receptor for advanced glycation end products (sRAGE) in the activation of AGE-RAGE axis, low levels of thiols, disulphide bonds formation and high nitrotyrosination in lupus nephritis. All these data help us to identify more molecular mechanisms to counteract oxidative stress in LN that could permit a more precise assessment of disease prognosis, as well as developing new therapeutic targets.

**Keywords:** systemic lupus erythematous; lupus nephritis; lipid peroxidation; DNA oxidation; oxidized proteins; carbohydrate oxidation; antioxidative stress strategies; biomarkers
