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Huntington's disease (HD) is a rare genetic neurodegenerative disorder caused by an expansion of CAG repeats in the Huntingtin (HTT) gene. One hypothesis suggests that the mutant HTT gene contributes to HD neuropathology through transcriptional dysregulation involving microRNAs (miRNAs). In particular, the miR-132/212 cluster is strongly diminished in the HD brain. This study explores the effects of miR-132/212 deficiency specifically in adult HD zQ175 mice. The absence of miR-132/212 did not impact body weight, body temperature, or survival rates. Surprisingly, miR-132/212 loss seemed to alleviate, in part, the effects on endogenous Htt expression, HTT inclusions, and neuronal integrity in HD zQ175 mice. Additionally, miR-132/212 depletion led to age-dependent improvements in certain motor functions. Transcriptomic analysis revealed alterations in HD-related networks in WT- and HD zQ175-miR-132/212-deficient mice, including significant overlap in BDNF and Creb1 signaling pathways. Interestingly, however, a higher number of miR-132/212 gene targets was observed in HD zQ175 mice lacking the miR-132/212 cluster, especially in the striatum. These findings suggest a nuanced interplay between miR-132/212 expression and HD pathogenesis, providing potential insights into therapeutic interventions. Further investigation is needed to fully understand the underlying mechanisms and therapeutic potential of modulating miR-132/212 expression during HD progression., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Nateghi, Keraudren, Boulay, Bazin, Goupil, Canet, Loiselle, St-Amour, Planel, Soulet and Hébert.)

Huntington's disease (HD) is an inherited neurodegenerative disorder caused by an expansion of CAG repeats in the Huntingtin (HTT) gene. Accumulating evidence suggests that the microtubule-associated tau protein participates in the pathogenesis of HD. Recently, we have identified changes in tau alternative splicing of exons 2, 3 and 10 in the putamen of HD patients (St-Amour et al, 2018). In this study, we sought to determine whether tau mis-splicing events were equally observed in other brain regions that are less prone to neurodegeneration. Using Western blot and PCR, we characterized the relationship between MAPT splicing of exons 2, 3 and 10, tauopathy and Htt pathologies, as well as neurodegeneration markers in matching putamen and cortical samples from HD (N = 48) and healthy control (N = 25) subjects. We first show that levels of 4R-tau (exon 10 inclusion) isoforms are higher in both the putamen and the cortex of individuals with HD, consistent with earlier findings. On the other hand, higher 0N-tau (exclusion of exons 2 and 3) and lower 1N-tau (exclusion of exon 3) isoforms were seen exclusively in the putamen of HD individuals. Interestingly, investigated splicing factors were deregulated in both regions whereas exon 2 differences coincided with increased tau hyperphosphorylation, aggregation and markers of neurodegeneration. Overall, these results imply a differential regulation of tau exon 2 and exon 10 alternative splicing in HD putamen that could provide a useful biomarker or therapeutic target., (Copyright © 2022 IBRO. All rights reserved.)

MicroARNAs (miRNAs) are linked to a variety of cancers, which resulted in molecular pathway dysregulation in chronic lymphocytic leukemia (CLL). Using five dysregulated miRNAs identified by literature mining and in silico analysis, we were able to demonstrate the critical role that the TGFBR1 and TGFB receptor signaling pathways play in the state of CLL. Assays using real-time PCR were run on 30 patients and 30 healthy controls. This study showed that patient samples have considerably higher levels of miR-574 and miR-499. Notably, the same groups had lower expression levels of miR-125b, miR-106a, and miR-9. Furthermore, we suggested that TGFBR1 and TGFBR2 expression levels were decreased in patients, and we suggested that these genes could be targets for our profile miRNAs. In the current study, we hypothesized that miR-574, miR-499, miR-125b, miR-106a, and miR-9 are likely five new potential biomarkers for early diagnosis. Our research also showed that these profile miRNAs have a role in the formation of CLL, possibly through controlling the TGFBR1 and TGFBR2 pathways. This suggests that these profile miRNAs could serve as biomarkers for the diagnosis and prognosis of CLL., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

Objective: Multiple sclerosis (MS) is a complex multifactorial neuro-inflammatory disorder. This complexity arises from the evidence suggesting that MS is developed by interacting with environmental and genetic factors. This study aimed to evaluate the miR-106a, miR-125b, and miR330- expression levels in relapsing-remitting multiple sclerosis (RRMS) patients. The miRNAs' impact on TNFSF4 and Sp1 genes through the NF-кB/TNF-α signaling pathway was analyzed by measuring the expression levels in case and controls., Materials and Methods: In this in silico-experimental study, we evaluated the association of miR-106a, miR- 125b, and miR330- with TNFSF4 and SP1 gene expression levels in 60 RRMS patients and 30 healthy controls by real-time polymerase chain reaction (PCR)., Results: The expression levels of miR-330, miR-106a, and miR125-b in blood samples of RRMS patients were predominantly reduced. The expression of TNFSF4 in patients demonstrated a significant enhancement, in contrast to the diminishing Sp1 gene expression level in controls., Conclusion: Our findings indicated an association between miR-106a and miR-330 and miR125-b expression and RRMS in our study population. Our data suggested that the miR106-a, miR125-b, and mir330- expression are correlated with TNFSF4 and Sp1 gene expression levels.

Altered microRNA (miRNA) expression is a common feature of Huntington's disease (HD) and could participate in disease onset and progression. However, little is known about the underlying causes of miRNA disruption in HD. We and others have previously shown that mutant Huntingtin binds to Ago2, a central component of miRNA biogenesis, and disrupts mature miRNA levels. In this study, we sought to determine if miRNA maturation per se was compromised in HD. Towards this end, we characterized major miRNA biogenesis pathway components and miRNA maturation products (pri-miRNA, pre-miRNA, and mature) in human HD (N = 41, Vonsattel grades HD2-4) and healthy control (N = 25) subjects. Notably, the striatum (putamen) and cortex (BA39) from the same individuals were analyzed in parallel. We show that Ago2, Drosha, and Dicer were strongly downregulated in human HD at the early stages of the disease. Using a panel of HD-related miRNAs (miR-10b, miR-196b, miR-132, miR-212, miR-127, miR-128), we uncovered various types of maturation defects in the HD brain, the most prominent occurring at the pre-miRNA to mature miRNA maturation step. Consistent with earlier findings, we provide evidence that alterations in autophagy could participate in miRNA maturation defects. Notably, most changes occurred in the striatum, which is more prone to HTT aggregation and neurodegeneration. Likewise, we observed no significant alterations in miRNA biogenesis in human HD cortex and blood, strengthening tissue-specific effects. Overall, these data provide important clues into the underlying mechanisms behind miRNA alterations in HD-susceptible tissues. Further investigations are now required to understand the biological, diagnostic, and therapeutic implications of miRNA/RNAi biogenesis defects in HD and related neurodegenerative disorders., (© 2022. The Author(s).)

A new porous coordination polymer (PCP/MOF), ZRTE-10 , based on a tetrahedral 1,3,5,7-tetra(carboxyphenyl)benzene ligand (H 4 L 4 ) was synthesized using formic or acetic acids as modulators. The low symmetry ( C 2/ c ) framework, [Zr 6 (μ 3 -O) 4 (μ 3 -OH) 4 (L 4 )(HL 4 ) 2 (OH) 2 (H 2 O) 2 ], is built upon a rare 10-connected Zr 6 cluster. Two-thirds of the ligands bear one nondeprotonated carboxy group, and the framework has a complex trinodal 3,4,10-c, {4 14 .6 24 .8 7 }{4 3 } 2 {4 5 .6}, underlying net. Supercritical CO 2 drying and mild degassing at 120 °C yielded a porous material with S BET = 1190 m 2 g -1 . When heated up to ∼200 °C, ZRTE-10 converts to another crystalline framework, ZRTE-11 . The latter was identified to be identical to the expected fluorite ( flu ) observed previously for other tetrahedral ligands. The high symmetry ( I 4/m) framework is built upon 8-connected Zr 6 clusters and has a formula of [Zr 6 (μ 3 -O) 4 (μ 3 -OH) 4 (OH) 4 (L 4 ) 2 ]. The complicated trinodal network of ZRTE-10 and the simple flu net in ZRTE-11 are topologically interrelated via the operation of the merging of two neighbor three-connected nodes to one four-connected one. The thermally induced conversion of ZRTE-10 proceeds with expulsion of one ligand per Zr 6 node in the pores of the framework, resulting in a relatively low S BET = 585 m 2 g -1 for the activated H 4 L 4 @ ZRTE-11 . A mixed ligand approach for ZRTE-10,11 was attempted using 1,3,5-tetra(carboxyphenyl)benzene (H 3 L 3 ), which is a truncated analog of H 4 L 4 with one missing branch. The monocrystalline sample of ZRTE-10 obtained in small yields demonstrated only minor inclusion of H 3 L 3 . However, the high-yielding (∼80%) procedure with HCl as a modulator allows near proportional incorporation of the ligands. The formed materials are semiamorphous with powder XRDs intermediary between pure ZRTE-10 and -11 . Thermal treatment of the semiamorphous materials increases their crystallinity and allows S BET = 400-550 m 2 g -1 surface areas to be reached for pure H 4 L 4 and H 3 L 3 or their mixture alike. The approach proposes a viewpoint on the H 3 L 3 trifunctional ligand as a model of a ligand platform, suitable for bearing a large functionality on the fourth "truncated" branch. The significance of ZRTE-10 as a material for postsynthetic introduction of metal-based cluster functionality and as a model of functionality encapsulation, an alternative to the ship-in-the-bottle method, is discussed.

Introduction: With the introduction of new surgical equipment, there is always the need for new, more advanced training. The authors try to answer whether the use of the newest generation tools has an impact on achieving better results in single incision laparoscopic surgery (SILS) technique during the exercises in the surgical skills laboratory., Material and Methods: There were 51 participants in the study: 44 'novices' and 7 'experts'. All subjects performed the 'advanced grasping' exercise according to the FLS programme manual using four types of laparoscopic approach including two SILS ports and SILS-dedicated instruments. The outcome measures involved task completion time and the number of errors., Results: Tasks using straight laparoscopic instruments set together with classic three-port access as well as SILS access ports were finished significantly faster when compared with SILS-dedicated instruments (p < 0.05). There were no significant differences in performance times between the two setups with straight instruments (p < 0.05) and both setups with SILS-dedicated instruments, irrespective of the use of curved or dynamic articulated tools. Students with no previous laparoscopic experience had significantly worse task completion times in all tasks in comparison to students with laparoscopic laboratory training and the 'experts' group., Conclusions: The use of the straight instruments in the SILS technique remain similar to its performance in full triangulation. SILS-dedicated instruments paradoxically increase the task completion time irrespective of possessed skills. The study showed the necessity of a SILS-dedicated tools training programme.