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Chronic kidney disease (CKD) is a global non-communicable health problem. Fibrosis is considered the base and the fate of CKD; thus, the goal of this study was to evaluate the effects of sodium molybdate on cisplatin-induced CKD model and demonstrate the possible involved mechanisms.

In cisplatin model, Wistar rats were challenged with cisplatin (1mg/kg, i.p.) twice weekly for ten weeks. Sodium molybdate (100 and 200mg/kg, orally) was given one-week prior cisplatin and was continued daily for the next ten weeks.

Administration of sodium molybdate amended kidney function and significantly reduced the pathological changes in renal histopathological sections. Moreover, it modulates oxidative stress parameters by increasing the levels of SOD and GSH and decreasing the level of MDA. Likewise, in renal homogenate, sodium molybdate attenuated inflammation that was revealed by NF-κB and TNF-α levels significant reduction. Additionally, it ameliorated fibrosis that was indicated by decreased Masson's trichome ste the inflammation through NF-κB and TNF-α levels reduction, decrease in ROS, and retrieval of antioxidant defenses.Cells are exposed to several environmental or chemical stressors that may cause DNA damage. DNA damage alters the normal functioning of the cell and contributes to several diseases, including cancer. Cells either induce DNA damage repair pathways or programmed cell death pathways to prevent disease formation depending on the severity of the stress and the damage caused. The DNA repair mechanisms are crucial to maintaining genome stability. During this adaptive response, the heat shock proteins (HSPs) are the key players. HSPs are overexpressed during genotoxic stress, but the role of different molecular players in the interaction between HSPs and DNA repair proteins is still poorly understood. As DNA damage promotes genomic instability and proteotoxic stress, modulating the protein quality control systems like the HSPs network could be a promising strategy for targeting disease pathologies associated with genomic instability, such as cancer. Hence, this review highlights the role of HSPs in DNA repair pathways. Further, the review also provides an outlook on the role of genomic instability and protein homeostasis in cancer, which is crucial to understanding the mechanisms behind its survival and developing novel targeted therapies.

Synthetic glucocorticoids, including dexamethasone (DEX), are clinically prescribed due to their immunoregulatory properties. In excess they can perturb glucose homeostasis, with individuals predisposed to glucose intolerance more sensitive to these negative effects. While DEX is known to negatively impact β-cell function, it is unclear how. Hence, our aim was to investigate the effect of DEX on β-cell function, both alone and in combination with a diabetogenic milieu in the form of elevated glucose and palmitate.

Human pancreatic EndoC-βH1 cells were cultured in the presence of high glucose and palmitate (glucolipotoxicity) and/or a pharmacological concentration of DEX, before functional and molecular analyses.

Either treatment alone resulted in reduced insulin content and secretion, while the combination of DEX and glucolipotoxicity promoted a strong synergistic effect. These effects were associated with reduced insulin biosynthesis, likely due to downregulation of PDX1, MAFA, and the proinsulin converting enzymes, as well as reduced ATP response upon glucose stimulation. Genome-wide DNA methylation analysis found changes on PDE4D, MBNL1 and TMEM178B, all implicated in β-cell function, after all three treatments. DEX alone caused very strong demethylation of the glucocorticoid-regulated gene ZBTB16, also known to influence the β-cell, while the combined treatment caused altered methylation of many known β-cell regulators and diabetes candidate genes.

DEX treatment and glucolipotoxic conditions separately alter the β-cell epigenome and function. The combination of both treatments exacerbates these changes, showing that caution is needed when prescribing potent glucocorticoids in patients with dysregulated metabolism.

DEX treatment and glucolipotoxic conditions separately alter the β-cell epigenome and function. The combination of both treatments exacerbates these changes, showing that caution is needed when prescribing potent glucocorticoids in patients with dysregulated metabolism.

Cyclophosphamide (CP) is a widely used chemotherapeutic drug. However, the associated nephrotoxicity restricts its clinical use.

The present research was designed to study the impact of LCZ696 (LCZ); which is a combination of Sacubitril/Valsartan compared to valsartan (VAL) on CP-induced nephrotoxicity.

Sixty adult male Wistar rats were randomly and equally assigned into 6 groups as follows Control, LCZ (30mg/kg, p.o.), VAL (15mg/kg, p.o.), CP (200mg/kg, single dose, i.p.), CP/LCZ, and CP/VAL groups. LCZ and VAL were given once daily for 6days prior to CP (groups 5 & 6). At the end of the experiment, kidney functions, oxidants/antioxidants, inflammatory and fibrotic biomarkers in renal tissues were assessed. Further, immunohistochemical, and histomorphometric analyses were carried out.

In comparison with CP-treated rats, LCZ resulted in a significant reduction in serum urea (26.6%) and creatinine (63%), moreover it decreased renal content of reactive oxygen species (ROS), zinc finger E-box-binding homeobox (ZEB)-1, SMAD2/3, plasminogen activator inhibitor (PAI)-1, fibronectin, histone deacetylase (HDAC)-4, nuclear factor-kappa B (NF-κB) and miR-192 expression by ~40-60% as well as the immunohistological expressions of transforming growth factor-β (TGF-β) and anti-phospho Histone (H2AX) by ~75% reduction. Tacedinaline Whereas the renal total antioxidant capacity (TAC), apelin-13, miR-200 expression, and the immunoreactivity of angiotensin-converting enzyme 2 (ACE2) were enhanced by ~3-4-folds. Noteworthy, the prophylactic effect of LCZ was superior to VAL on the histomorphometric and immunohistological levels.

Prophylactic administration of LCZ protected against CP-induced nephrotoxicity via up-regulating apelin-13/ACE2, miR-200, and down-regulating TGF-β/SMAD 2/3 and miR-192.

Prophylactic administration of LCZ protected against CP-induced nephrotoxicity via up-regulating apelin-13/ACE2, miR-200, and down-regulating TGF-β/SMAD 2/3 and miR-192.

Postpartum depression (PPD) is a serious mental health concern affecting approximately 17.22 % of new mothers worldwide. In addition to its obstetric effects, oxytocin (OXT) has also been considered to play a role in PPD. However, most previous studies exploring associations between PPD and OXT levels focus on easier accessible compartments such as blood or saliva.

To explore the possible association between PPD and OXT levels, and to assess the interaction between peripheral secretion and central release of OXT.

In this study, we prospectively measured OXT concentrations in cerebrospinal fluid (CSF), plasma and saliva of 94 women with elective cesarean section by enzyme-linked immunosorbent assay (ELISA) kits. The participants were divided into the PPD group if the score of Edinburgh Postpartum Depression Scale (EPDS)≥10 at 3months postpartum, otherwise into the non-PPD (nPPD) group.

The incidence of PPD was 30.85%. OXT concentrations in CSF (r=-0.518, p<0.001), plasma (r=-0.240, p=0.020) and saliva (r=-0.263, p=0.010) were negatively correlated with EPDS score, and were valuable for the prediction of PPD, with AUC and 95%CI of 0.890 (0.809-0.945), 0.683 (0.579-0.775) and 0.699 (0.596-0.790), respectively. Moreover, OXT concentrations in plasma (r=0.407, p<0.001) and saliva (r=0.624, p<0.001) were positively correlated with CSF OXT concentrations.

Only full-term pregnant women undergoing elective cesarean section were included in this study, which may affect study generalizability.

The central and peripheral release of OXT is coordinated, and OXT level measured prenatally in CSF, plasma, or saliva is valuable for the prediction of PPD.

The central and peripheral release of OXT is coordinated, and OXT level measured prenatally in CSF, plasma, or saliva is valuable for the prediction of PPD.The impact of new technology can be appreciated by how broadly it is used. Investigators that previously relied only on pharmacological approaches or the use of morpholino antisense oligonucleotide (MASO) technologies are now able to apply CRISPR-Cas9 to study biological problems in their model organism of choice much more effectively. The transitions to new CRISPR-based approaches could be enhanced, first, by standardized protocols and education in their applications. Here we summarize our results for optimizing the CRISPR-Cas9 technology in a sea urchin and a sea star, and provide advice on how to set up CRISPR-Cas9 experiments and interpret the results in echinoderms. Our goal through these protocols and sharing examples of success by other labs is to lower the activation barrier so that more laboratories can apply CRISPR-Cas9 technologies in these important animals.The vertebrate embryonic midline vasculature forms in close proximity to the developing skeletal muscle, which originates in the somites. Angioblasts migrate from bilateral positions along the ventral edge of the somites until they meet at the midline, where they sort and differentiate into the dorsal aorta and the cardinal vein. This migration occurs at the same time that myoblasts in the somites are beginning to differentiate into skeletal muscle, a process which requires the activity of the basic helix loop helix (bHLH) transcription factors Myod and Myf5. Here we examined vasculature formation in myod and myf5 mutant zebrafish. In the absence of skeletal myogenesis, angioblasts migrate normally to the midline but form only the cardinal vein and not the dorsal aorta. The phenotype is due to the failure to activate vascular endothelial growth factor ligand vegfaa expression in the somites, which in turn is required in the adjacent angioblasts for dorsal aorta specification. Myod and Myf5 cooperate with Hedgehog signaling to activate and later maintain vegfaa expression in the medial somites, which is required for angiogenic sprouting from the dorsal aorta. Our work reveals that the early embryonic skeletal musculature in teleosts evolved to organize the midline vasculature during development.

Appropriate and consistent facial protective equipment (FPE) use is critical for preventing respiratory illness transmission. Little is known about FPE adherence by home care providers. The purpose of this study is to adapt an existing facial protection questionnaire and use it to develop an initial understanding of factors influencing home care providers' adherence to FPE during the COVID-19 pandemic.

A survey was shared with home care providers during Wave 2 of the COVID-19 pandemic in Ontario. Descriptive statistics and logistic regression by FPE adherence were conducted across individual, organizational, and environmental factors.

Of the 199 respondents (140 personal support workers; 59 nurses), 71% reported that they always used FPE as required, with greater adherence to masks (89%) than eye protection (73%). The always-adherent reported greater perceived FPE efficacy, knowledge of recommended use and perceived occupational risk, lower education, and not experiencing personal barriers (including difficulty seeing, discomfort, communication challenges).