Depression, Somatization and Anxiety in Female Patients with Temporomandibular Disorders (TMD)

The aim of this research was to determine the possible differences in degrees of depression, somatization and anxiety between the acute and chronic female patients with temporomandibular disorders (TMD), and whether these differences exist in healthy female patients. Ninety female patients were involved in this research; 60 of them were TMD patients of the Dental Polyclinic, while other 30 females came for a rutine recall visit and had no problem related to TMD. Patients were aged 22 to 67 years, the average age being 38.5±12 years. All patients were asked to fill in the RDC/TMD protocol and three psychological tests (Emotions Profile Index, Somatization Scale and life Events Scale). Following the analysis of the RDC/TMD protocol and psychological tests, it was determined that the chronic female patients had higher depression and somatization scores in comparison with the acute patients (p<0.01); the acute patients self-perceive higher levels of anxiety in relation to the control group; furthermore, the patients reporting higher levels of depression were more inclined to somatization and had experienced a greater number of stress events in the past six months. It is beyond doubt that patients suffering from the TMD’s exhibit higher levels of depression, somatization and anxiety compared to the healthy ones, which proves that physiological factors may play a predisposing role in combination with reduced level of body tolerance to pain, and a decreased tolerance to stress

Afstudeerwerk

Voorwoord bij een nieuwe rubriek met afstudeerwerk Het Bulletin KNOB biedt een podium aan zowel ervaren onderzoekers als aanstormend talent. Met een zekere regelmaat publiceren afgestudeerden een artikel op basis van hun masterscriptie of ander onderzoek dat zij aan de universiteit deden. Maar dit is slechts een topje van de ijsberg. Er is immers veel meer werk van studenten dat de aandacht van de lezer verdient. Daarom starten wij in het Bulletin KNOB een rubriek met afstudeerwerk. Eens in de twee jaar vragen wij een aantal pas afgestudeerden van wie de masterthesis of eindopdracht goed is beoordeeld hiervan een synthese te maken. Voor de eerste aflevering van deze rubriek zijn dat degenen die meedongen naar de KNOB Stimuleringsprijs 2021. Het resultaat vindt u in dit nummer: zeventien bijdragen over uiteenlopende onderwerpen, van Cubex-keuken tot herbestemming van industrieel erfgoed en van klimaatverbetering in steden tot Antwerpse zeemanshuizen. De auteurs zijn alumni van universitaire opleidingen op het gebied van architectuur- en stadsgeschiedenis, erfgoed en (landschaps)architectuur in Nederland en België. Met deze rubriek laten wij onze lezers kennisnemen van door studenten verricht onderzoek en bieden wij beginnende onderzoekers en ontwerpers een gelegenheid hun werk in het Bulletin KNOB te presenteren. Onze dank gaat daarbij uit naar collega Jeroen Goudeau, die ons het idee voor een rubriek met afstudeerwerk aan de hand deed. Wij wensen u veel leesplezier en inspiratie toe. De redactieVoorwoord bij een nieuwe rubriek met afstudeerwerk Het Bulletin KNOB biedt een podium aan zowel ervaren onderzoekers als aanstormend talent. Met een zekere regelmaat publiceren afgestudeerden een artikel op basis van hun masterscriptie of ander onderzoek dat zij aan de universiteit deden. Maar dit is slechts een topje van de ijsberg. Er is immers veel meer werk van studenten dat de aandacht van de lezer verdient. Daarom starten wij in het Bulletin KNOB een rubriek met afstudeerwerk. Eens in de twee jaar vragen wij een aantal pas afgestudeerden van wie de masterthesis of eindopdracht goed is beoordeeld hiervan een synthese te maken. Voor de eerste aflevering van deze rubriek zijn dat degenen die meedongen naar de KNOB Stimuleringsprijs 2021. Het resultaat vindt u in dit nummer: zeventien bijdragen over uiteenlopende onderwerpen, van Cubex-keuken tot herbestemming van industrieel erfgoed en van klimaatverbetering in steden tot Antwerpse zeemanshuizen. De auteurs zijn alumni van universitaire opleidingen op het gebied van architectuur- en stadsgeschiedenis, erfgoed en (landschaps)architectuur in Nederland en België. Met deze rubriek laten wij onze lezers kennisnemen van door studenten verricht onderzoek en bieden wij beginnende onderzoekers en ontwerpers een gelegenheid hun werk in het Bulletin KNOB te presenteren. Onze dank gaat daarbij uit naar collega Jeroen Goudeau, die ons het idee voor een rubriek met afstudeerwerk aan de hand deed. Wij wensen u veel leesplezier en inspiratie toe. De redacti

THO complex deficiency impairs DNA double-strand break repair via the RNA surveillance kinase SMG-1

The integrity and proper expression of genomes are safeguarded by DNA and RNA surveillance pathways. While many RNA surveillance factors have additional functions in the nucleus, little is known about the incidence and physiological impact of converging RNA and DNA signals. Here, using genetic screens and genome-wide analyses, we identified unforeseen SMG-1-dependent crosstalk between RNA surveillance and DNA repair in living animals. Defects in RNA processing, due to viable THO complex or PNN-1 mutations, induce a shift in DNA repair in dividing and non-dividing tissues. Loss of SMG-1, an ATM/ATR-like kinase central to RNA surveillance by nonsense-mediated decay (NMD), restores DNA repair and radio-resistance in THO-deficient animals. Mechanistically, we find SMG-1 and its downstream target SMG-2/UPF1, but not NMD per se, to suppress DNA repair by non-homologous end-joining in favour of single strand annealing. We postulate that moonlighting proteins create short-circuits in vivo, allowing aberrant RNA to redirect DNA repair

Modulating mutational outcomes and improving precise gene editing at CRISPR-Cas9-induced breaks by chemical inhibition of end-joining pathways

Gene editing through repair of CRISPR-Cas9-induced chromosomal breaks offers a means to correct a wide range of genetic defects. Directing repair to produce desirable outcomes by modulating DNA repair pathways holds considerable promise to increase the efficiency of genome engineering. Here, we show that inhibition of non-homologous end joining (NHEJ) or polymerase theta-mediated end joining (TMEJ) can be exploited to alter the mutational outcomes of CRISPR-Cas9. We show robust inhibition of TMEJ activity at CRISPR-Cas9-induced double-strand breaks (DSBs) using ART558, a potent polymerase theta (Polϴ) inhibitor. Using targeted sequencing, we show that ART558 suppresses the formation of microhomology-driven deletions in favor of NHEJ-specific outcomes. Conversely, NHEJ deficiency triggers the formation of large kb-sized deletions, which we show are the products of mutagenic TMEJ. Finally, we show that combined chemical inhibition of TMEJ and NHEJ increases the efficiency of homology-driven repair (HDR)-mediated precise gene editing. Our work reports a robust strategy to improve the fidelity and safety of genome engineering

Modulating mutational outcomes and improving precise gene editing at CRISPR-Cas9-induced breaks by chemical inhibition of end-joining pathways

Summary: Gene editing through repair of CRISPR-Cas9-induced chromosomal breaks offers a means to correct a wide range of genetic defects. Directing repair to produce desirable outcomes by modulating DNA repair pathways holds considerable promise to increase the efficiency of genome engineering. Here, we show that inhibition of non-homologous end joining (NHEJ) or polymerase theta-mediated end joining (TMEJ) can be exploited to alter the mutational outcomes of CRISPR-Cas9. We show robust inhibition of TMEJ activity at CRISPR-Cas9-induced double-strand breaks (DSBs) using ART558, a potent polymerase theta (Polϴ) inhibitor. Using targeted sequencing, we show that ART558 suppresses the formation of microhomology-driven deletions in favor of NHEJ-specific outcomes. Conversely, NHEJ deficiency triggers the formation of large kb-sized deletions, which we show are the products of mutagenic TMEJ. Finally, we show that combined chemical inhibition of TMEJ and NHEJ increases the efficiency of homology-driven repair (HDR)-mediated precise gene editing. Our work reports a robust strategy to improve the fidelity and safety of genome engineering

CAR-NK Cells Targeting HER1 (EGFR) Show Efficient Anti-Tumor Activity against Head and Neck Squamous Cell Carcinoma (HNSCC)

(1) Background: HNSCC is a highly heterogeneous and relapse-prone form of cancer. We aimed to expand the immunological tool kit against HNSCC by conducting a functional screen to generate chimeric antigen receptor (CAR)-NK-92 cells that target HER1/epidermal growth factor receptor (EGFR). (2) Methods: Selected CAR-NK-92 cell candidates were tested for enhanced reduction of target cells, CD107a expression and IFNγ secretion in different co-culture models. For representative HNSCC models, patient-derived primary HNSCC (pHNSCC) cell lines were generated by employing an EpCAM-sorting approach to eliminate the high percentage of non-malignant cells found. (3) Results: 2D and 3D spheroid co-culture experiments showed that anti-HER1 CAR-NK-92 cells effectively eliminated SCC cell lines and primary HNSCC (pHNSCC) cells. Co-culture of tumor models with anti-HER1 CAR-NK-92 cells led to enhanced degranulation and IFNγ secretion of NK-92 cells and apoptosis of target cells. Furthermore, remaining pHNSCC cells showed upregulated expression of putative cancer stem cell marker CD44v6. (4) Conclusions: These results highlight the promising potential of CAR-NK cell therapy in HNSCC and the likely necessity to target multiple tumor-associated antigens to reduce currently high relapse rates

Identification of microRNAs in skeletal muscle associated with lung cancer cachexia

BACKGROUND: Cachexia, highly prevalent in patients with non-small cell lung cancer (NSCLC), impairs quality of life and is associated with reduced tolerance and responsiveness to cancer therapy and decreased survival. MicroRNAs (miRNAs) are small non-coding RNAs that play a central role in post-transcriptional gene regulation. Changes in intramuscular levels of miRNAs have been implicated in muscle wasting conditions. Here, we aimed to identify miRNAs that are differentially expressed in skeletal muscle of cachectic lung cancer patients to increase our understanding of cachexia and to allow us to probe their potential as therapeutic targets. METHODS: A total of 754 unique miRNAs were profiled and analysed in vastus lateralis muscle biopsies of newly diagnosed treatment-naïve NSCLC patients with cachexia (n = 8) and age-matched and sex-matched healthy controls (n = 8). miRNA expression analysis was performed using a TaqMan MicroRNA Array. In silico network analysis was performed on all significant differentially expressed miRNAs. Differential expression of the top-ranked miRNAs was confirmed using reverse transcription-quantitative real-time PCR in an extended group (n = 48) consisting of NSCLC patients with (n = 15) and without cachexia (n = 11) and healthy controls (n = 22). Finally, these miRNAs were subjected to univariate and multivariate Cox proportional hazard analysis using overall survival and treatment-induced toxicity data obtained during the follow-up of this group of patients. RESULTS: We identified 28 significant differentially expressed miRNAs, of which five miRNAs were up-regulated and 23 were down-regulated. In silico miRNA-target prediction analysis showed 158 functional gene targets, and pathway analysis identified 22 pathways related to the degenerative or regenerative processes of muscle tissue. Subsequently, the expression of six top-ranked miRNAs was measured in muscle biopsies of the entire patient group. Five miRNAs were detectable with reverse transcription-quantitative real-time PCR analysis, and their altered expression (expressed as fold change, FC) was confirmed in muscle of cachectic NSCLC patients compared with healthy control subjects: miR-424-5p (FC = 4.5), miR-424-3p (FC = 12), miR-450a-5p (FC = 8.6), miR-144-5p (FC = 0.59), and miR-451a (FC = 0.57). In non-cachectic NSCLC patients, only miR-424-3p was significantly increased (FC = 5.6) compared with control. Although the statistical support was not sufficient to imply these miRNAs as individual predictors of overall survival or treatment-induced toxicity, when combined in multivariate analysis, miR-450-5p and miR-451a resulted in a significant stratification between short-term and long-term survival. CONCLUSIONS: We identified differentially expressed miRNAs putatively involved in lung cancer cachexia. These findings call for further studies to investigate the causality of these miRNAs in muscle atrophy and the mechanisms underlying their differential expression in lung cancer cachexia