BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder that progresses over time. Fourier Transform Infrared Spectroscopy (FTIR) analysis gives identification of the main metabolic changes that happen during neurodegeneration, by monitoring biochemical and molecular structure alterations that can help in AD diagnosis or treatment approach.

OBJECTIVE: The aim of the present work is to assess AD hallmarks in molecular structure of retina and monitor accumulation of amyloid beta(Aβ) in brain and retina during disease progression.

METHODS: AD induced in rats by Aluminum Chloride (AlCl). Retinal molecular structure during disease progression for 2,4,6 and 8 weeks was assessed by Fourier-transform infrared spectroscopy (FTIR) and the incidence of the disease was confirmed by a behavioural assessment; the Morris Water Maze test. Aβ levels in the brain and retina were also measured.

RESULTS: The results indicated that cognitive impairment starting from 6 weeks of AlCl administration. Retinal concentration of Aβ was significant increase ( < 0.05) from 2 weeks that precedes the observed increase of Aβ in the brain which appeared after 4 weeks of AlCl administration. Multivariate principal component analysis discovers that the variance noticed in the infrared spectra due to AD condition and it is time dependent for progression of the disease.

CONCLUSIONS: The accumulation of Aβ is a sensitive early biomarker in retina for AD. FTIR analysis of the retina revealed changes in hydrogen bond formation or destruction, alterations in lipid chain length and branching accompanied by depleted lipid content and carbonization, as well as degeneration of the retinal tissue due to AD.

Lipoid congenital adrenal hyperplasia (LCAH) is characterized by disturbance of adrenal and gonadal steroidogenesis (OMIM:201710). It is caused by mutation in the Steroidogenic Acute Regulatory Protein (StAR). We report a classic case of LCAH in a neonate (46, XY) with phenotypic female genitalia who presented with significant salt loss with a novel homozygous variant mutation c.745-1G>C p. in StAR gene.

Chemotherapy-accompanied reproductive dysfunction has lately begun to draw the attention of the scientific community owing to the irreversible impact on the patient's quality of life. Here we tended to investigate the potential role of liraglutide (LRG) in modulating the canonical Hedgehog (Hh) signaling in doxorubicin (DXR)-induced gonadotoxicity in rats. Female virgin Wistar rats were divided into 4 groups; control, DXR-treated (25 mg/kg, single i.p. injection), LRG-treated (150 μg/Kg/day, s.c) and itraconazole (ITC; 150 mg/kg/day, p.o)-pretreated group, as the Hh pathway inhibitor. Treatment with LRG potentiated the PI3K/AKT/p-GSK3β cascade and relieved the oxidative burden-induced by the DXR-driven immunogenic cell death (ICD). LRG also upregulated the expression of the Desert hedgehog ligand (DHh) and the patched-1 (PTCH1) receptor and augmented the protein level of Indian hedgehog (IHh) ligand, Gli1 and cyclin-D1 (CD1). Besides, hypertranscription of IHh, DHh, Ptch1, Smo, Gli1/2 and CD1 genes along with a transcriptional recession of Gli3 gene were reported in LRG-treated group. ITC pre-administration partially abrogated this positive effect of LRG, proving the implication of the examined pathway. Microscopically, LRG ameliorated the follicular atresia noticed in the DXR group; effect that was, at least partially, declined by ITC pre-treatment. These findings end to a conclusion that LRG treatment might hinder the DXR-associated reproductive toxicity, resultant from ROS generated by the cells undergoing ICD, and trigger follicular growth and repair by the PI3K/AKT- dependent switching-on of the canonical Hh pathway.

Psoriasis is a persistent inflammatory skin disorder driven by T cells. The disease is characterized by aberrant keratinocytes (KCs) differentiation, epidermal proliferation, and excessive hyperplasia of veins and arteries. The purpose of the study was to identify the levels of circulating , , and Sirtuin 1 () in psoriatic patients, evaluate their possible roles as diagnostic biomarkers, and link their levels with the development of metabolic syndrome during psoriasis progression. This study included 176 participants. The subjects were divided into four groups, with 44 participants in each group. All patients have undergone a complete history taking and clinical examination. Laboratory investigations included Low-density lipoprotein (LDL), High-density lipoprotein (HDL), Triglycerides (TG), Fasting blood sugar (FBS), and cholesterol plasma levels. Serum levels of and were examined by qRT-PCR. Serum levels of were examined by ELISA. The serum concentrations of and were significantly higher in psoriatic participants compared to controls. Psoriatic patients' serum concentrations of were much lower than those of healthy individuals. There was a negative association between concentration and BMI, disease duration, PASI score, LDL, and cholesterol levels. The blood levels of , , and in psoriasis patients provide a promising role as diagnostic biomarkers in patients with and without metabolic syndrome.

Accumulating evidence has shown an abnormal expression of several non-coding RNAs in ovarian tissues which might be closely linked with the pathogenesis of PCOS. The aim of this study was to identify competing endogenous (ce) RNA network: long non-coding RNA (lncRNA), microRNA (miRNA) and their target genes: androgen receptor (AR), follistatin (FST) and insulin receptor substrate-2 (IRS-2), which are relevant to PCOS, to underline the molecular pathogenesis of PCOS and assist in early diagnosis and treatment. Bioinformatic analysis was performed to retrieve a ceRNA network: [lncRNA (NEAT1 and MALAT1) - miRNA (miR-30a-5p and miR-30d-5p) - mRNA (AR, FST and IRS-2)] linked to PCOS. Expression of the selected RNAs was examined by qPCR in peripheral blood leukocytes obtained from 73 PCOS patients (41 obese and 32 non-obese) and 31 healthy controls. PCOS patients showed significantly higher expression levels of NEAT1, miR-30a-5p, AR, FST and IRS-2, with significantly lower expression levels of MALAT1 and miR-30d-5p relative to controls especially in obese versus non-obese patients. Receiver operating characteristic (ROC) curve analysis indicated that most of the selected RNAs could serve as potential early diagnostic markers for PCOS with the highest efficiency obtained upon combining NEAT1 and miR-30d-5p or MALAT1 and miR-30a-5p with either of PCOS target genes. Moreover, all addressed RNAs had been proved as potential predictors of PCOS. The obtained data of ceRNA network raised the possibility that NEAT1 overexpression may increase the expression levels of AR, FST and IRS-2 by sponging miR-30d-5p, while low expression of MALAT1 may allow higher expression of the above genes via increasing miR-30a-5p, suggesting their involvement in PCOS pathogenesis and promising role for future diagnosis and targeted therapy.

Accumulating evidence has shown an abnormal expression of several non-coding RNAs in ovarian tissues which might be closely linked with the pathogenesis of PCOS. The aim of this study was to identify competing endogenous (ce) RNA network: long non-coding RNA (lncRNA), microRNA (miRNA) and their target genes: androgen receptor (AR), follistatin (FST) and insulin receptor substrate-2 (IRS-2), which are relevant to PCOS, to underline the molecular pathogenesis of PCOS and assist in early diagnosis and treatment. Bioinformatic analysis was performed to retrieve a ceRNA network: [lncRNA (NEAT1 and MALAT1) - miRNA (miR-30a-5p and miR-30d-5p) - mRNA (AR, FST and IRS-2)] linked to PCOS. Expression of the selected RNAs was examined by qPCR in peripheral blood leukocytes obtained from 73 PCOS patients (41 obese and 32 non-obese) and 31 healthy controls. PCOS patients showed significantly higher expression levels of NEAT1, miR-30a-5p, AR, FST and IRS-2, with significantly lower expression levels of MALAT1 and miR-30d-5p relative to controls especially in obese versus non-obese patients. Receiver operating characteristic (ROC) curve analysis indicated that most of the selected RNAs could serve as potential early diagnostic markers for PCOS with the highest efficiency obtained upon combining NEAT1 and miR-30d-5p or MALAT1 and miR-30a-5p with either of PCOS target genes. Moreover, all addressed RNAs had been proved as potential predictors of PCOS. The obtained data of ceRNA network raised the possibility that NEAT1 overexpression may increase the expression levels of AR, FST and IRS-2 by sponging miR-30d-5p, while low expression of MALAT1 may allow higher expression of the above genes via increasing miR-30a-5p, suggesting their involvement in PCOS pathogenesis and promising role for future diagnosis and targeted therapy.

INTRODUCTION: Ulcerative colitis (UC) is a chronic disease that alters the colonic and rectal mucosa. The high prevalence rates of UC make it a worldwide healthcare problem. However, its underlying molecular mechanisms remain vague.

AIM OF THE STUDY: To investigate the molecular mechanisms underlying UC and to study the cross-talk among the regulatory role of the lncRNAs UCA1, CRNDE, and miR-145 on TLR4/NF-κB/TNF-α signaling pathway. Moreover, the study was extended to examine the beneficial effects of 3,3-Diindolylmethane (DIM) on relieving UC.

METHODS: UC was induced in rats by injecting 2 ml of 4% acetic acid (AA) solution transrectally. After 24 h, rats were treated with either DIM (20 mg/kg) or sulphasalazine (SSZ) (500 mg/kg) orally for 7 days.

RESULTS: The present study revealed that the gene expression of the lncRNAs UCA1 and CRNDE were significantly upregulated in the AA-induced UC model compared with the control group, whereas miR-145 was significantly downregulated. There was a significant association between the expression of these non-coding RNAs and TLR4/ NF-κB/TNF-α axis as well as malondialdehyde and glutathione levels. Favorably, the DIM-treated group showed significant downregulation of the lncRNAs UCA1 and CRNDE along with upregulated miR-145 compared with the AA-induced UC model. Furthermore, DIM showed remarkable inhibition of the TLR4/ NF-κB /TNF-α cascade compared with non-treated UC rats.

CONCLUSIONS: The present study is the first to document the interrelated role of the lncRNAs UCA1 and CRNDE in UC via orchestrating miR-145/TLR4/ NF-κB /TNF-α inflammatory cascade. Furthermore, the study demonstrated a new molecular basis for the pleiotropic activities of DIM in relieving UC.