Potential role of the lncRNA "HOTAIR"/miRNA "206"/BDNF network in the alteration in expression of synaptic plasticity gene arc and BDNF level in sera of patients with heroin use disorder through the PI3K/AKT/mTOR pathway compared to the controls.

INTRODUCTION: Heroin use disorder (HUD) is a seriously increasing health issue, accounting for most deaths among drug abusers. Studying non-coding ribonucleic acid gene expression among drug abusers is a promising approach, as it may be used in diagnosis and therapeutics. PARTICIPANTS AND METHODS: A total of 49 male heroin-dependent patients and 49 male control participants were recruited from Kasr Al Ainy Psychiatry and Addiction outpatient clinics, Faculty of Medicine, Cairo University. Sera were gathered. qRT-PCR was utilized for the detection of gene expression of non-coding RNAs such as "HOX transcript antisense RNA" (HOTAIR), micro-RNA (miRNA-206), phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), mechanistic target of rapamycin (mTOR), and Activity Regulated Cytoskeleton Associated Protein (Arc). Sera Brain-Derived Neurotrophic Factor (BDNF) levels were assessed using ELISA. Using a western blot made it possible to determine the protein expression of PI3K, AKT, and mTOR. RESULTS: The study demonstrated that gene expressions of HOTAIR, AKT, PI3K, and Arc were considerably lowered between cases and controls, while gene expressions of miR-206 and mTOR1 were significantly raised. PI3K and AKT protein expressions were downregulated, while mTOR expressions were upregulated. BDNF levels were significantly decreased in some cases. CONCLUSION: The results of this study suggest that decreased HOTAIR in HUD relieves miR-206 inhibition, which thus increases and affects downstream PI3K/AKT/mTOR, ARC, and BDNF expression. This may be shared in addictive and relapsing behaviors.

Expression patterns of lncRNA MALAT-1 in SARS-COV-2 infection and its potential effect on disease severity via miR-200c-3p and SIRT1.

Downregulating Angiotensin Converting Enzyme2 (ACE2) expression may be a shared mechanism for RNA viruses. Aim: Evaluate the expressions of ACE2 effectors: the long non-coding RNA 'MALAT-1', the micro-RNA 'miR-200c-3p' and the histone deacetylase 'SIRT1' in SARS-COV-2 patients and correlate to disease severity. Sera samples from 98 SARS-COV-2 patients and 30 healthy control participants were collected. qRT-PCR was used for MALAT-1 and miR-200c-3p expression. SIRT1 was measured using ELISA. Results: In sera of COVID-19 patients, gene expression of miR-200c-3p is increased while MALAT-1 is decreased. SIRT1 protein level is decreased (P value < 0.001). Findings are accentuated with increased disease severity. Serum MALAT-1, miR-200c-3p and SIRT1 could be used as diagnostic markers at cut off values of 0.04 (95.9 % sensitivity), 5.59 (94.9 % sensitivity, 99 % specificity), and 7.4 (98 % sensitivity) respectively. A novel MALAT-1-miR-200c-3p-SIRT1 pathway may be involved in the regulation of SARS-COV-2 severity.

Evaluating the protective role of trimetazidine versus nano-trimetazidine in amelioration of bilateral renal ischemia/reperfusion induced neuro-degeneration: Implications of ERK1/2, JNK and Galectin-3 /NF-κB/TNF-α/HMGB-1 signaling.

BACKGROUND: Renal ischemia/reperfusion (I/R) is a primary culprit of acute kidney injury. Neurodegeneration can result from I/R, but the mechanisms are still challenging. We studied the implications of bilateral renal I/R on brain and potential involvement of the oxidative stress (OS) driven extracellular signal-regulated kinase1/2, c-Jun N-terminal kinase (ERK1/2, JNK) and Galectin-3 (Gal-3)/nuclear factor Kappa B (NF-қB)/tumor necrosis factor-alpha (TNF-α), high mobility group box-1 (HMGB-1), and caspase-3 paths upregulation. We tested the impact of Nano-trimetazidine (Nano-TMZ) on these pathways being a target of its neuroprotective effects. METHODS: Study groups; Sham, I/R, TMZ+I/R, and Nano-TMZ+I/R. Kidney functions, cognition, hippocampal OS markers, Gal-3, NF-қB, p65 and HMGB-1 gene expression, TNF-α level, t-JNK/p-JNK and t-ERK/p-ERK proteins, caspase-3, glial fibrillary acidic protein (GFAP) and ionized calcium binding protein-1 (Iba-1) were assessed. RESULTS: Nano-TMZ averted renal I/R-induced hippocampal impairment by virtue of its anti: oxidative, inflammatory, and apoptotic properties. CONCLUSION: Nano-TMZ is more than anti-ischemic.

Hydrogen sulfide modulates SIRT1 and suppresses oxidative stress in diabetic nephropathy.

DN is recognized as not only a leading cause of end stage renal disease (ESRD) but also an independent risk factor for cardiovascular disease (CVD). Novel therapeutic approaches to diabetic nephropathy (DN) are needed, or else, healthcare resources will be overwhelmed by the expected worldwide increase in associated cases of ESRD and CVD. Reactive oxygen species (ROS) and advanced glycation end product (AGE) are implicated in the development of DN. Hydrogen sulfide (H2S) is known for its antioxidant and antiapoptotic characteristics. Simultaneously diabetics have lower H2S levels. Thus, it is worth investigating the use of H2S in treatment of DN. To investigate the potential therapeutic role of H2S in DN. Sixty male rats were divided into four groups: control, DN, DN+NaHS30 µmol/kg/day and DN+NaHS100 µmol/kg/day. Fasting blood sugar (FBS), kidney function tests, SIRT1 activity, superoxide dismutase activity (SOD), malondialdehyde (MDA) and expression of caspase3 and p53 in renal tissues were assessed. Kidney was examined histopathologically. DN rats had higher FBS, renal dysfunction, decreased SIRT1 and SOD activity levels, increased caspase3 and p53 relative expression and increased MDA in renal tissues. NaHS increased SIRT1 and reversed biochemical, apoptotic, oxidant and pathologic parameters characteristic of DN, with better results using a dose of 100 µmol/kg/day. H2S has a protective role against DN through decreasing FBS, ROS, apoptosis and upregulating SIRT1, thus preserving renal cells from further damage caused by DM.