👤 Pouya Taheri

Depression is a widespread neuropsychiatric disorder that significantly impacts emotional and cognitive function. Antidepressant medications are frequently accompanied by various adverse effects. C-phycocyanin has been previously shown to exert potent anti-inflammatory, and neuroprotective properties. Therefore, this study evaluated the therapeutic effects of C-phycocyanin against anxiety and depressive-like behaviors, and memory dysfunction in an animal model of chronic unpredictable mild stress (CUMS)-induced depression and explored the underlying mechanisms. Rats were daily exposed for six weeks to CUMS, during which phycocyanin (100 mg/kg, orally) was administered in the final three weeks of the study. Following the assessment of anxiety/ depressive-like behaviors, and memory dysfunction by the open field test (OFT), tail suspension test (TST), elevated plus maze (EPM), and passive avoidance test (PAT), rats were euthanized by decapitation. Then, hippocampal TNF-α and IL-1β concentrations, and hippocampal protein expressions (Iba-1, CD86, NF-κβ, CREB, and BDNF) were determined by an ELISA assay, and western blots, respectively. C-phycocyanin significantly decreased immobility time in OFT and TST, increased open arm time in EPM, and step-through latency time in PAT. Furthermore, C-phycocyanin suppressed CUMS-induced the M1 microglia polarization and neuroinflammation by reducing hippocampal TNF-α and IL-1β concentrations, and the protein expression of Iba-1, CD86, and NF-κβ in the hippocampus of CUMS-exposed rats. It also increased the hippocampal protein expression of CREB and BDNF. C-phycocyanin improved CUMS-induced anxiety and depressive-like behaviors, and memory dysfunction, which could be explained, at least in part, by inhibition of M1 microglial polarization and neuroinflammation, and enhancement of CREB/BDNF signaling. Show less

First-line immune checkpoint inhibitor (ICI) combinations show responses in subsets of hepatocellular carcinoma (HCC) patients. Nearly half of HCCs are Wnt-active with mutations in CTNNB1 (encoding for β-catenin), AXIN1/2, or APC, and demonstrate heterogeneous and limited benefit to ICI due to an immune excluded tumor microenvironment. We show significant tumor responses in multiple β-catenin-mutated immunocompetent HCC models to a novel siRNA encapsulated in lipid nanoparticle targeting CTNNB1 (LNP-CTNNB1). Both single-cell and spatial transcriptomics reveal cellular and zonal reprogramming, along with activation of immune regulatory transcription factors IRF2 and POU2F1, re-engaged type I/II interferon signaling, and alterations in both innate and adaptive immunity upon β-catenin suppression with LNP-CTNNB1 at early- and advanced-stage disease. Moreover, ICI enhances response to LNP-CTNNB1 in advanced-stage disease by preventing T cell exhaustion and through formation of lymphoid aggregates (LA). In fact, expression of an LA-like gene signature prognosticates survival for patients receiving atezolizumab plus bevacizumab in the IMbrave150 phase III trial and inversely correlates with CTNNB1-mutatational status in this patient cohort. In conclusion, LNP-CTNNB1 is efficacious as monotherapy and in combination with ICI in CTNNB1-mutated HCCs through impacting tumor cell-intrinsic signaling and remodeling global immune surveillance, providing rationale for clinical investigations. Show less

Schiff bases derived from 3-acetyl-4-hydroxycoumarin represent a promising yet underexplored scaffold in medicinal chemistry. Here, we report the efficient synthesis of a series of bisimine derivatives (3a-j) through condensation with structurally diverse amines, achieving yields of 68-95%. Spectroscopic characterization (NMR, IR, MS) confirmed their unique architectures, with 3j emerging as a standout candidate exhibiting anticancer activity comparable to doxorubicin but with superior selectivity against MCF-7 and A549 cell lines. Among the tested derivatives, compound 3a exhibited the most potent antibacterial activity, with the lowest MIC values observed against Gram-positive strains. Notably, 3f (a thiourea analog) demonstrated broad-spectrum antifungal efficacy (MICs: 1.95-31.25 µg/mL), while 3c surpassed ascorbic acid in radical scavenging (96.7% DPPH inhibition). Molecular docking revealed robust interactions between lead compounds (3b, 3c, 3j) and key therapeutic targets (FGFR1, cIAP1-BIR3), suggesting a dual inhibitory mechanism. These findings underscore the potential of coumarin bisimines as versatile platforms for addressing antibiotic resistance and oxidative stress-related pathologies. Show less

Primary breast lymphomas (PBLs) are rare tumors that originate in the breast without systemic disease at diagnosis. Lymphoplasmacytic lymphoma (LPL), usually associated with Waldenström's macroglobulinemia, is exceptionally uncommon in this location. We report a case of a 36-year-old woman with no significant medical history who presented with a rapidly enlarging right breast mass. Imaging revealed a suspicious right breast lesion classified as Breast Imaging Reporting and Data System (BI-RADS) Category 4. Core needle biopsy with histopathology and immunohistochemistry confirmed CD20-negative LPL, an indolent B-cell lymphoma. The patient was treated with bendamustine-based chemotherapy and corticosteroids, with marked clinical and radiological improvement. This case emphasizes the importance of considering hematologic malignancies in the differential diagnosis of breast lesions to avoid unnecessary surgical management and ensure appropriate systemic therapy. Show less

Clearance of accumulated protein aggregates is one of the functions of autophagy. Recently, a clearer understanding of non-coding RNAs (ncRNAs) functions documented that ncRNAs have important roles in several biological processes associated with the development and progression of neurodegenerative disorders. Subtypes of ncRNA, including microRNA (miRNA), long noncoding RNA (lncRNA), and circular RNA (circRNA), are commonly dysregulated in neurodegenerative disorders such as Alzheimer and Parkinson diseases. Dysregulation of these non-coding RNAs has been associated with inhibition or stimulation of autophagy. Decreased miR-124 led to decreased/increased autophagy in experimental model of Alzheimer and Parkinson diseases. Increased BACE1-AS showed enhanced autophagy in Alzheimer disease by targeting miR-214-3p, Beclin-1, LC3-I/LC3-II, p62, and ATG5. A significant increase in NEAT1led to stimulated autophagy in experimental model of PD by targeting PINK1, LC3-I, LC3-II, p62 and miR-374c-5p. In addition, increased BDNF-AS and SNHG1 decreased autophagy in MPTP-induced PD by targeting miR-125b-5p and miR-221/222, respectively. The upregulation of circNF1-419 and circSAMD4A resulted in an increased autophagy by regulating Dynamin-1 and miR-29c 3p, respectively. A detailed discussion of miRNAs, circRNAs, and lncRNAs in relation to their autophagy-related signaling pathways is presented in this study. Show less

Schizophrenia (SCZ) is a serious mental condition with an unknown cause. According to the reports, Brodmann Area 10 (BA10) is linked to the pathology and cortical dysfunction of SCZ, which demonstrates a number of replicated findings related to research on SCZ and the dysfunction in tasks requiring cognitive control in particular. Genetics' role in the pathophysiology of SCZ is still unclear. Therefore, it may be helpful to understand the effects of these changes on the onset and progression of SCZ to find novel mechanisms involved in the regulation of gene transcription. In order to determine the molecular regulatory mechanisms affecting the SCZ, the long non-coding RNA (lncRNA)-associated competing endogenous RNAs (ceRNAs) axes in the BA10 area were determined using a bioinformatics approach in the present work. A microarray dataset (GSE17612) consisted of brain post-mortem tissues of the BA10 area from SCZ patients and matched healthy subjects was downloaded from the Gene Expression Omnibus (GEO) database. This dataset included probes for both lncRNAs and mRNAs. Using the R software's limma package, the differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) were found. The RNA interactions were also discovered using the DIANA-LncBase and miRTarBase databases. In the ceRNA network, positive correlations between DEmRNAs and DElncRNAs were evaluated using the Pearson correlation coefficient. Finally, lncRNA-associated ceRNA axes were built by using the co-expression and DElncRNA-miRNA-DEmRNA connections. We identified the DElncRNA-miRNA-DEmRNA axes, which included two key lncRNAs ( Show less

Hypertension is a multifactorial condition in which several genetic and environmental elements contribute. Recent investigations have revealed contribution of non-coding region of the transcriptome in this trait. CDKN2B-AS1, AK098656, MEG3, H19, PAXIP1-AS1, TUG1, GAS5, CASC2 and CPS1-IT are among long non-coding RNAs participating in the pathophysiology of hypertension. Several miRNAs have also been found to be implicated in this disorder. miR-296, miR-637, miR-296, miR-637, hsa-miR-361-5p, miR-122-5p, miR-199a-3p, miR-208a-3p, miR-423-5p, miR-223-5p and miR-140-5p are among dysregulated miRNAs in this condition whose application as diagnostic biomarkers for hypertension has been evaluated. Finally, hsa-circ-0005870, hsa_circ₀₀₃₇₉₁₁ and hsa_circ₀₀₁₄₂₄₃ are examples of dysregulated circular RNAs in hypertensive patients. In the current review, we describe the role of these non-coding RNAs in the pathophysiology of hypertension. Show less

Kleine-Levin syndrome (KLS) is characterized by relapsing-remitting episodes of hypersomnia, cognitive impairment, and behavioral disturbances. We quantified cerebrospinal fluid (CSF) and serum proteins in KLS cases and controls. SomaScan was used to profile 1133 CSF proteins in 30 KLS cases and 134 controls, while 1109 serum proteins were profiled in serum from 26 cases and 65 controls. CSF and serum proteins were both measured in seven cases. Univariate and multivariate analyses were used to find differentially expressed proteins (DEPs). Pathway and tissue enrichment analyses (TEAs) were performed on DEPs. Univariate analyses found 28 and 141 proteins differentially expressed in CSF and serum, respectively (false discovery rate <0.1%). Upregulated CSF proteins included IL-34, IL-27, TGF-b, IGF-1, and osteonectin, while DKK4 and vWF were downregulated. Pathway analyses revealed microglial alterations and disrupted blood-brain barrier permeability. Serum profiles show upregulation of Src-family kinases (SFKs), proteins implicated in cellular growth, motility, and activation. TEA analysis of up- and downregulated proteins revealed changes in brain proteins (p < 6 × 10-5), notably from the pons, medulla, and midbrain. A multivariate machine-learning classifier performed robustly, achieving a receiver operating curve area under the curve of 0.90 (95% confidence interval [CI] = 0.78-1.0, p = 0.0006) in CSF and 1.0 (95% CI = 1.0-1.0, p = 0.0002) in serum in validation cohorts, with some commonality across tissues, as the model trained on serum sample also discriminated CSF samples of controls versus KLS cases. Our study identifies proteomic KLS biomarkers with diagnostic potential and provides insight into biological mechanisms that will guide future research in KLS. Show less

End-stage renal disease (ESRD) is a public health problem with a high burden. The condition is associated with abnormalities in lipid metabolism. The fatty acid desaturase (FADS) gene cluster includes three genes that are significantly correlated with a number of pathologic conditions related to abnormal lipid levels. In the current study, we genotyped rs174556, rs99780, and rs7115739 single nucleotide polymorphisms within the Show less

Hepatocellular carcinoma (HCC) is among the utmost deadly human malignancies. This type of cancer has been associated with several environmental, viral, and lifestyle risk factors. Among the epigenetic factors which contribute in the pathogenesis of HCC is dysregulation of long non-coding RNAs (lncRNAs). These transcripts modulate expression of several tumor suppressor genes and oncogenes and alter the activity of cancer-related signaling axes. Several lncRNAs such as NEAT1, MALAT1, ANRIL, and SNHG1 have been up-regulated in HCC samples. On the other hand, a number of so-called tumor suppressor lncRNAs namely CASS2 and MEG3 are down-regulated in HCC. The interaction between lncRNAs and miRNAs regulate expression of a number of mRNA coding genes which are involved in the pathogenesis of HCC. H19/miR-15b/CDC42, H19/miR-326/TWIST1, NEAT1/miR-485/STAT3, MALAT1/miR-124-3p/Slug, MALAT1/miR-195/EGFR, MALAT1/miR-22/SNAI1, and ANRIL/miR-144/PBX3 axes are among functional axes in the pathobiology of HCC. Some genetic polymorphisms within non-coding regions of the genome have been associated with risk of HCC in certain populations. In the current paper, we describe the recent finding about the impact of lncRNAs in HCC. Show less

Epithelial to mesenchymal transition (EMT) is a course of action that enables a polarized epithelial cell to undertake numerous biochemical alterations that allow it to adopt features of mesenchymal cells such as high migratory ability, invasive properties, resistance to apoptosis, and importantly higher-order formation of extracellular matrix elements. EMT has important roles in implantation and gastrulation of the embryo, inflammatory reactions and fibrosis, and transformation of cancer cells, their invasiveness and metastatic ability. Regarding the importance of EMT in the invasive progression of cancer, this process has been well studies in in this context. Non-coding RNAs (ncRNAs) have been shown to exert critical function in the regulation of cellular processes that are involved in the EMT. These processes include regulation of some transcription factors namely SNAI1 and SNAI2, ZEB1 and ZEB2, Twist, and E12/E47, modulation of chromatin configuration, alternative splicing, and protein stability and subcellular location of proteins. In the present paper, we describe the influence of ncRNAs including microRNAs and long non-coding RNAs in the EMT process and their application as biomarkers for this process and cancer progression and their potential as therapeutic targets. Show less

Cholesteryl ester transfer protein (CETP) inhibitors increase serum high-density lipoprotein cholesterol (HDL-c) concentration; however, their impact on cardiovascular outcomes is not clear. This systematic review examines the effect of CETP inhibitors on serum lipid profiles, cardiovascular events, and all-cause mortality. We searched MEDLINE, Embase, and the Cochrane Library of Clinical Trials for placebo-controlled randomized controlled trials (RCTs) that examined the effect of a CETP inhibitor (dalcetrapib, anacetrapib, evacetrapib, or TA-8995) on all-cause mortality, major adverse cardiovascular events (MACE), or the components of MACE at ≥6 months. Data were pooled using random-effects models. A total of 11 RCTs (n = 62,431) were included in our systematic review; 4 examined dalcetrapib (n = 16,612), 6 anacetrapib (n = 33,682), and 1 evacetrapib (n = 12,092). Compared to dalcetrapib, ana-cetrapib and evacetrapib were more efficacious at raising HDL-c levels (∼100-130 vs. ∼30%). Anacetrapib and evacetrapib also decreased low-density lipoprotein cholesterol (LDL-c) by approximately 30% while dalcetrapib did not affect the LDL-c level. Overall, CETP inhibitors were not associated with the incidence of MACE (pooled relative risk [RR]: 0.97; 95% confidence interval [CI]: 0.91-1.04). CETP inhibitors may decrease the risks of nonfatal myocardial infarction (MI) (RR: 0.93; 95% CI: 0.87-1.00) and cardiovascular death (RR: 0.92; 95% CI: 0.83-1.01), though these trends did not reach statistical significance. CETP inhibitors are not associated with an increased risk of MACE or all-cause mortality. There is a trend towards small reductions in nonfatal MI and cardiovascular death, though the clinical im-portance of such reductions is likely modest. Show less