MicroRNA-29a (miR-29a) has been shown to ameliorate hepatocellular damage, such as in the context of non-alcoholic fatty liver disease (NAFLD), steatohepatitis (NASH), and cholestatic injury. However, the mechanism mediating the hepatoprotective effect of miR-29a in diet-induced NASH remains elusive. In the present study, C57BL/6 mice of wild-type (WT) or miR-29a overexpression were fed with methionine-choline sufficient (MCS) or methionine-choline-deficient (MCD) diet for four weeks. The C57BL/6 mice harboring miR-29a overexpression presented reduced plasma AST, hepatic CD36, steatosis, and fibrosis induced by MCD. The TargetScan Release7.2-based bioinformatic analysis, KEGG pathway analysis, and luciferase reporter assay confirmed that miR-29a targets 3'UTR of glycogen synthase kinase 3 beta (Gsk3b) mRNA in the HepG2 hepatocyte cell line. Furthermore, miR-29a overexpression in the MCD-fed group resulted in inhibition of Gsk3b mRNA and GSK3β protein levels in the liver. GSK3β was notably expressed jointly with the extent of aggregated protein, which was then identified to be associated with mitochondrial unfolded protein response (UPRmt), but not with endoplasmic reticulum UPR (UPRER). Additionally, in silico analysis of protein-protein interaction, in vivo, and in vitro correlation analyses of protein expression demonstrated that GSK3β closely associated with sirtuin 1(SIRT1). Finally, the implication of SIRT1-mediated mitochondrial biogenesis in the perturbation of proteostasis was observed. We herein provide novel insight into a hepatoprotective pathway, whereby miR-29a inhibits GSK3β to repress SIRT1-mediated mitochondrial biogenesis, leading to alleviation of mitochondrial proteostatic stress and UPRmt in the context of NASH. miR-29a, GSK3β, and SIRT1 could thus serve as possible therapeutic targets to improve the treatment of NAFLD/NASH.In patients with stage III colon cancer (CC), adjuvant chemotherapy with the combination of oxapliplatin to a fluoropyrimidine (FOLFOX or CAPOX) is a standard of care. The duration of treatment can be reduced from 6 months to 3 months, depending on the regimen, for patients at low risk of recurrence, without loss of effectiveness and allowing a significant reduction in the risk of cumulative sensitive neuropathy. However, our capacity to identify patients that do really need this doublet adjuvant treatment remains limited. In fact, only 30% at the most will actually benefit from this adjuvant treatment, 50% of them being already cured by the surgery and 20% of them experiencing disease recurrence despite the adjuvant treatment. Thus, it is necessary to be able to better predict individually for each patient the risk of recurrence and the need for adjuvant chemotherapy together with the need of new treatment approaches for specific subgroups. Many biomarkers have been described with their own prognostic weight, without leading to any change in clinical practices for now. In this review, we will first discuss the recommendations for adjuvant chemotherapy, and then the different biomarkers described and the future perspectives for the management of stage III CC.First-generation cysteine-based site-specific antibody-drug conjugates (ADCs) are limited to one drug per cysteine. However, certain applications require a high drug to antibody ratio (DAR), such as when low-potency payloads are used. Higher drug load can be achieved using classical cysteine conjugation methods, but these result in heterogeneity, suboptimal efficacy and pharmacokinetics. Here, we describe the design, synthesis and validation of heterobifunctional linkers that can be used for the preparation of ADCs with a DAR of two, three and four in a site-specific manner per single cysteine conjugation site, resulting in site-specific ADCs with a DAR of four, six and eight. The designed linkers carry a sulfhydryl-specific iodoacetyl reactive group, and multiple cyclic diene moieties which can efficiently react with maleimide-carrying payloads through the Diels-Alder reaction. As a proof of concept, we synthesized site-specific DAR four, six and eight ADCs carrying tubulysin (AZ13601508) using engineered antibodies with a cysteine inserted after position 239 in the antibody CH2 domain. We evaluated and compared the in vitro cytotoxicity of ADCs obtained via the site-specific platform described herein, with ADCs prepared using classical cysteine conjugation. Our data validated a novel cysteine-based conjugation platform for the preparation of site-specific ADCs with high drug load for therapeutic applications.The abilities of children diagnosed with Obstetric Brachial Palsy (OBP) are limited by brachial plexus injuries. Thus, their participation in the community is hindered, which involves a lower quality of life due to worse performance in activities of daily living as a consequence of the functional limitations of the affected upper limb. Conventional Mirror Therapy (Conventional MT) and Virtual Therapy improve the affected upper limb functionality. Therefore, the aim of this study was to compare the effects of Conventional MT and Virtual Reality MT on the spontaneous use of the affected upper limb and quality of life of children with upper Obstetric Brachial Palsy between 6 and 12 years of age. A randomized pilot study was performed. Twelve children were randomly assigned to perform Conventional Mirror Therapy or Virtual Reality Mirror Therapy for four weeks. Ten children completed the treatment. Two assessments (pre/post-intervention) were carried out to assess the spontaneous use of the affected upper limb an would be a home-based therapeutic complement to increase independent bimanual tasks using grasp in the affected upper limb and improve the quality of life of children diagnosed with upper OBP in the age range of 6-12 years.Psoriasis is a long-term skin disorder without a cure, whose patients are particularly susceptible to mental health diseases. Using a sample of patients diagnosed with psoriasis, this study aimed to (1) identify the clinical and positive psychological variables that contribute the most to psoriasis disability and (2) assess the mediator role of body image-related cognitive fusion in the relation between disease severity perception and acceptance and self-compassion, on one hand, and psoriasis disability on the other. This is an initial cross-sectional exploratory study, with 75 patients diagnosed with psoriasis (males 52%; mean age 54.99 ± 13.72) answering a sociodemographic and a clinical questionnaire, the Psoriasis Disability Index (PDI), the Cognitive Fusion Questionnaire-Body Image (CFQ-BI), the Acceptance and Action Questionnaire-II (AAQ-II), and the Self-Compassion Scale (SCS).  https://www.selleckchem.com/products/dexketoprofen-trometamol.html  Descriptive and inferential statistics were used to characterize and assess the measures and the final model used. Through path analysis and a hierarchical multiple linear regression, it was found that the variables that significantly contributed to psoriasis disability were years of education, impact on social life and body image, explaining 70% of the variance.