Corrigendum: Inhibition of coronavirus HCoV-OC43 by targeting the eIF4F complex.

[This corrects the article DOI: 10.3389/fphar.2022.

Association of plasma endocan levels with metabolic parameters and predictive value of endocan for the development of complications in patients with type 2 diabetes mellitus: An observational study.

The aim of the current research was to investigate the association between plasma endocan levels and metabolic control parameters, as well as to evaluate its predictive value for clinical complications in patients with type 2 diabetes mellitus (DMT2). A total of 100 DMT2 patients participated in this prospective observational study. Plasma endocan levels were significantly elevated in DMT2 patients with HbA1c > 7% (1.

Targeting eIF4G1-dependent translation in melanoma.

Elevated expression of components of eIF4F translation initiation complex has been documented in cancer, resulting in enhanced translation of mRNAs encoding pro-tumorigenic factors, including oncogenic proteins. We previously identified SBI-756, a small molecule that interferes with the eIF4F assembly and overcomes melanoma resistance to BRAF inhibitors. SBI-756 enhanced anti-tumor immunity in pancreatic cancer and was effective in the treatment of diffuse large B cell lymphoma.

Analysis of excessive corticosteroid use as an indicator of poor quality of care in patients with inflammatory bowel disease.

Aim: To evaluate the clinical impact of corticosteroids (CS) overuse in inflammatory bowel disease (IBD) patients. Excessive use of CS could delay more efficacious treatment and may indicate poor quality of care.

Method: This is a two-phase study that used Steroid Assessment Tool (SAT) to measure corticosteroid exposure in IBD patients.

SMYD5 methylation of rpL40 links ribosomal output to gastric cancer.

Dysregulated transcription due to disruption in histone lysine methylation dynamics is an established contributor to tumorigenesis. However, whether analogous pathologic epigenetic mechanisms act directly on the ribosome to advance oncogenesis is unclear. Here we find that trimethylation of the core ribosomal protein L40 (rpL40) at lysine 22 (rpL40K22me3) by the lysine methyltransferase SMYD5 regulates mRNA translation output to promote malignant progression of gastric adenocarcinoma (GAC) with lethal peritoneal ascites.

Short-term efficacy of vedolizumab in patients with inflammatory bowel disease in real-life settings in Bosnia and Herzegovina.

Inflammatory bowel disease (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), necessitates effective management strategies. This study aims to evaluate the real-world efficacy of vedolizumab, a newer biological therapy, in treating IBD in Bosnia and Herzegovina. A retrospective observational study was conducted across six medical centers, involving 139 IBD patients, 76 with UC and 63 with CD.

MTOR modulation induces selective perturbations in histone methylation which influence the anti-proliferative effects of mTOR inhibitors.

Emerging data suggest a significant cross-talk between metabolic and epigenetic programs. However, the relationship between the mechanistic target of rapamycin (mTOR), which is a pivotal metabolic regulator, and epigenetic modifications remains poorly understood. Our results show that mTORC1 activation caused by the abrogation of its negative regulator tuberous sclerosis complex 2 (TSC2) coincides with increased levels of the histone modification H3K27me3 but not H3K4me3 or H3K9me3.

A second-generation eIF4A RNA helicase inhibitor exploits translational reprogramming as a vulnerability in triple-negative breast cancer.

In this study, we aimed to address the current limitations of therapies for macro-metastatic triple-negative breast cancer (TNBC) and provide a therapeutic lead that overcomes the high degree of heterogeneity associated with this disease. Specifically, we focused on well-documented but clinically underexploited cancer-fueling perturbations in mRNA translation as a potential therapeutic vulnerability. We therefore developed an orally bioavailable rocaglate-based molecule, MG-002, which hinders ribosome recruitment and scanning via unscheduled and non-productive RNA clamping by the eukaryotic translation initiation factor (eIF) 4A RNA helicase.

Myeloid cell ACE shapes cellular metabolism and function in PCSK-9 induced atherosclerosis.

The pathogenesis of atherosclerosis is defined by impaired lipid handling by macrophages which increases intracellular lipid accumulation. This dysregulation of macrophages triggers the accumulation of apoptotic cells and chronic inflammation which contributes to disease progression. We previously reported that mice with increased macrophage-specific angiotensin-converting enzyme, termed ACE10/10 mice, resist atherosclerosis in an adeno-associated virus-proprotein convertase subtilisin/kexin type 9 (AAV-PCSK9)-induced model.

A sex-specific thermogenic neurocircuit induced by predator smell recruiting cholecystokinin neurons in the dorsomedial hypothalamus.

Olfactory cues are vital for prey animals like rodents to perceive and evade predators. Stress-induced hyperthermia, via brown adipose tissue (BAT) thermogenesis, boosts physical performance and facilitates escape. However, many aspects of this response, including thermogenic control and sex-specific effects, remain enigmatic.

Inhibition of coronavirus HCoV-OC43 by targeting the eIF4F complex.

The translation initiation complex 4F (eIF4F) is a rate-limiting factor in protein synthesis. Alterations in eIF4F activity are linked to several diseases, including cancer and infectious diseases. To this end, coronaviruses require eIF4F complex activity to produce proteins essential for their life cycle.

Distinct, opposing functions for CFIm59 and CFIm68 in mRNA alternative polyadenylation of Pten and in the PI3K/Akt signalling cascade.

Precise maintenance of PTEN dosage is crucial for tumor suppression across a wide variety of cancers. Post-transcriptional regulation of Pten heavily relies on regulatory elements encoded by its 3'UTR. We previously reported the important diversity of 3'UTR isoforms of Pten mRNAs produced through alternative polyadenylation (APA).

Sustained chemogenetic activation of locus coeruleus norepinephrine neurons promotes dopaminergic neuron survival in synucleinopathy.

Dopaminergic neuron degeneration in the midbrain plays a pivotal role in motor symptoms associated with Parkinson's disease. However, non-motor symptoms of Parkinson's disease and post-mortem histopathology confirm dysfunction in other brain areas, including the locus coeruleus and its associated neurotransmitter norepinephrine. Here, we investigate the role of central norepinephrine-producing neurons in Parkinson's disease by chronically stimulating catecholaminergic neurons in the locus coeruleus using chemogenetic manipulation.

Mitochondrial complex IV defects induce metabolic and signaling perturbations that expose potential vulnerabilities in HCT116 cells.

Mutations in genes encoding cytochrome c oxidase (mitochondrial complex IV) subunits and assembly factors [e.g., synthesis of cytochrome c oxidase 2 (SCO2)] are linked to severe metabolic syndromes.

Olfactory system and energy metabolism: a two-way street.

Olfactory perception guides daily decisions regarding food consumption, social interactions, and predator avoidance in all mammalian species. Volatile inputs, comprising odorants and pheromones, are relayed to the olfactory bulb (OB) from nasal sensory neurons cells and transferred to secondary processing regions within the brain. Olfaction has recently been shown to shape homeostatic and maladaptive processes of energy intake and expenditure through neuronal circuits involving the medial basal hypothalamus.

PABP prevents the untimely decay of select mRNA populations in human cells.

Gene expression is tightly regulated at the levels of both mRNA translation and stability. The poly(A)-binding protein (PABP) is thought to play a role in regulating these processes by binding the mRNA 3' poly(A) tail and interacting with both the translation and mRNA deadenylation machineries. In this study, we directly investigate the impact of PABP on translation and stability of endogenous mRNAs in human cells.

Fragment-type 4-azolylcoumarin derivatives with anticancer properties.

Several coumarin derivatives with a directly attached azole substituent at C-4 were synthesized and biologically studied for their anticancer properties. The cell lines used for this investigation (HeLa, K-562, MDA-MB-53, and MCF-7) demonstrated different sensitivities. The best response in the MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide) assay was shown by K-562 cells, with compounds displaying activity (3c, IC 3.

Sensory neurons expressing calcitonin gene-related peptide α regulate adaptive thermogenesis and diet-induced obesity.

Objectives: Heat-sensory neurons from the dorsal root ganglia (DRG) play a pivotal role in detecting the cutaneous temperature and transmission of external signals to the brain, ensuring the maintenance of thermoregulation. However, whether these thermoreceptor neurons contribute to adaptive thermogenesis remains elusive. It is also unknown whether these neurons play a role in obesity and energy metabolism.

Synthesis, characterization, antimicrobial and cytotoxic activity of novel half-sandwich Ru(II) arene complexes with benzoylthiourea derivatives.

Three new ruthenium(II)-arene complexes, [Ru(η-p-cymene)(L)Cl] (C1) where L is N-((4 methoxyphenyl)carbamothioyl)benzamide; [Ru(η-p-cymene)(L)Cl] (C2) where L is 4-(3-benzoylthioureido)benzoic acid and [Ru(η-p-cymene)(L)Cl] (C3) where L is methyl 4-(3- benzoylthioureido)benzoate have been synthetized, characterized and evaluated for their antimicrobial and anticancer activity. Characterization was performed using H and C NMR, IR spectroscopy, mass spectrometry, electrical conductivity measurements and X-Ray diffraction analysis. X-Ray diffraction analysis of C1 showed typical expected "piano-stool" geometry with ruthenium coordinated to ligand via nitrogen and sulfur atoms of benzoylthiourea derivatives.

Melatonin treatment affects changes in adrenal gene expression of catecholamine biosynthesizing enzymes and norepinephrine transporter in the rat model of chronic-stress-induced depression.

This study investigated the effects of melatonin treatment on adrenal catecholamine content, synthesis, uptake, and vesicular transport induced by the chronic unpredictable mild stress (CUMS) model of depression in rats. This entailed quantifying the norepinephrine, epinephrine, mRNA, and protein levels of tyrosine hydroxylase (TH), dopamine-β-hydroxylase (DBH), phenylethanolamine -methyltransferase (PNMT), norepinephrine transporter (NET), and vesicular monoamine transporter 2 (VMAT2) in the adrenal medulla. CUMS caused a significant depletion of norepinephrine stores and protein levels of TH, DBH, and NET, whereas the gene expression of PNMT was increased.

Oxytocin modulates the expression of norepinephrine transporter, β-adrenoceptors and muscarinic M receptors in the hearts of socially isolated rats.

Social stress produces behavioral alterations, and autonomic and cardiac dysfunction in animals. In addition to the well-known roles of oxytocin on birth and maternal bonding, recent evidence shows that this neuropeptide possesses cardio-protective properties. However less is known about its role in the regulation of the autonomic nervous system.

Preparation of pyrrolizinone derivatives via sequential transformations of cyclic allyl imides: synthesis of quinolactacide and marinamide.

A facile synthetic route has been developed for the preparation of pyrrolizinone derivatives employing N-allyl imides as starting materials. The nucleophilic addition of a vinyl Grignard reagent/RCM/elimination sequence afforded pyrrolizinones in good yields and has been applied for the preparation of naturally occurring quinolactacide and marinamide.

Foveal Avascular Zone in Normal Tension Glaucoma Measured by Optical Coherence Tomography Angiography.

Aim: To measure diameter of foveal avascular zone (FAZ), FAZ area, and vessel density using Optical Coherence Tomography Angiography (OCT-A) in patients with normal tension glaucoma (NTG) and to establish the possible role of OCT-A in diagnosis and follow-up of patients with NTG.

Methods: Twenty-one eyes of 21 patients with NTG and 30 eyes of 30 healthy subjects underwent complete ophthalmic examination as well as OCT-A on ZEISS AngioPlex. 3 × 3 macula scans were used to measure vertical, horizontal, and maximum diameter of FAZ by two graders.

Altered cardiac gene expression of noradrenaline enzymes, transporter and β-adrenoceptors in rat model of rheumatoid arthritis.

Baseline sympathetic activity was found to be elevated in rheumatoid arthritis (RA) patients and it is related to increased cardiovascular risk in these patients. Although many studies have highlighted the association between RA and increased cardiac sympathetic activity, the underlying mechanistic links remain unclear. The aim of the present study was to understand how diseases-triggered changes in gene expression may result in maladaptive physiological changes.