Neurodegenerative diseases such as Alzheimer´s (AD) and physiological ageing are characterized by a decline in neurogenesis and in the polysialylated isoforms of neural cell adhesion molecule (PSA-NCAM) expression within the hippocampus and specifically in the dentate gyrus (DG). In the 3xTG-AD mouse model, which mimics the human disease in both pathological and behavioral features, this decline in PSA-NCAM is associated with the presence of Aβ plaques at 9 months and Tau tangles at 12-15 months. In this work we studied the presence of PSA-NCAM at early ages (1-6 months) in the same model. Our results demonstrated that even as early as the first month of age there is a strong decrease in PSA-NCAM dendritic tree mainly altering the molecular layer (MolL) coverage affecting the synaptic plasticity and furthermore confirmed by the reduction of PSA-NCAM area density (Sv) in the 3xTG-AD. Similar and more marked early changes were seen during aging in both NTG and 3xTg-AD animals. Our results demonstrate for the first time a precipitate decrease of PSA-NCAM cells at such very early phases of the disease. This result suggests an early effect of the disease in the progression of immature and pluripotent cells resulting in an ulterior and early diminution of neurogenesis and therefore an impaired hippocampal cellular and synaptic plasticity.

Gestational diabetes mellitus is a common medical complication during pregnancy. It creates a hyperglycemic environment and impacts offspring development, increasing the risk of long-term complications, including obesity, impaired glucose metabolism and cardiovascular disease. The impact of gestational diabetes on the prostates of adult offspring has already been described; however, it is not known whether these effects are due only to the maternal condition or whether the offspring develop them throughout life. This investigation evaluated the prostates of neonatal and juvenile offspring of hyperglycemic rats due to diabetes. Diabetes was induced with streptozotocin (50 mg/kg, ip) in pregnant Wistar rats and the prostates of 7- or 30-day-old pups from healthy (PC7, PC30) or diabetic (PD7, PD30) mothers were evaluated. We found reduced body weight in pups of PD7 and PD30 and prostate weight in PD30. Prostate branching was not affected, but a reduction in apoptotic levels was associated with impaired acinar bud canalization in neonates. Additionally, PD7 presented reduced ERK1/2 phosphorylation, cell proliferation and collagen, but fibroblasts were increased. In PD30, there was a reduction in the area of the secretory epithelium and stroma, but the luminal area was increased. Moreover, fibroblasts, smooth muscle cells, collagen and metalloproteinase 2 were decreased in these juvenile pups. These data indicate that maternal hyperglycemia inactivates an important cell proliferation signaling pathway in the prostate in the first postnatal days (which is restored in the juvenile period), but it was not sufficient to avoid epithelial and stromal atrophy. This effect on postnatal gland development may impact the reproductive capacity of the prostate in adult life.

Nuclear factor erythroid 2-related factor-2 (Nrf2) is a specific transcription factor that maintains redox homeostasis by regulating the expression of anti-oxidative stress-related genes. Hyperactivation of Nrf2 is involved in tumor progression and is associated with chemoresistance in a large number of solid tumors. Programmatic cell death (PCD), such as apoptosis, ferroptosis, and autophagy, plays a crucial role in tumor development and chemotherapy sensitivity. Accumulating evidence suggests that some anti-tumor compounds and genes can induce massive production of reactive oxygen species (ROS) via inhibiting Nrf2 expression, which exacerbates oxidative stress and promotes Gastric cancer (GC) cell death, thereby enhancing the sensitivity of GC cells to chemotherapy-induced PCD. In this review, we summarize the role of antitumor drugs in interfering in three different types of PCD (apoptosis, ferroptosis, and autophagy) in GC cells by modulating Nrf2 expression, as well as the molecular mechanisms through which targeting Nrf2 brings about PCD and chemosensitivity. It is reasonable to believe that Nrf2 serves as a potential therapeutic target, and targeting Nrf2 by drug or gene regulation could provide a new strategy for the treatment of GC.

Diabetic nephropathy is the leading cause of end-stage kidney disease, and the association between impaired autophagy and kidney structure damage in diabetes is well known. Diets enriched with polyunsaturated fatty acids (PUFAs) have been the subject of numerous studies on preventing and treating various metabolic disorders. The results of these studies suggest that n-3 PUFA may have a renoprotective effect, reducing the structural damage to the kidneys associated with DM. We hypothesized that the activation of autophagy partly mediates the potential protective effect of n-3 PUFA on diabetic kidneys. Wistar rats were randomly divided into four groups according to the type of diet: control (C) and diabetic (STZ) groups received food including 0.5 % linseed oil and 2 % sunflower oil with an n-6/n-3 ratio of 7; the STZ+N6 group received a diet with 2.5 % sunflower oil with an n-6/n-3 ratio of 60; and the STZ+N3 group received a diet containing 2.5 % fish oil with an n-6/n-3 ratio of 1, with the addition of eicosapentaenoic acid (EPA) and 19 % docosahexaenoic acid (DHA). All rats, except for those in the C group, had diabetes induced by an intraperitoneal injection of streptozotocin. We conducted histological and immunohistochemical assessments to determine the effects of different n-6/n-3 PUFA dietary ratios on the expression levels of different autophagy markers in the kidney of the rats. The results indicate significant effects of n-3 and n-6 PUFA supplementation on the expression of different autophagy markers in the renal cortex of the diabetic rats. In particular, n-6 PUFA supplementation increased LC3B expression while simultaneously decreasing Rab7 expression; meanwhile, n-3 PUFA supplementation resulted in a decreased expression of LAMP2A and Rab7. Moreover, n-3 PUFA supplementation prevented an increase in BECL1 and p62, that was observed in kidneys from diabetic and diabetic n-3 supplemented animals. These results point to the complex interactions of fatty acids and autophagy during the development of diabetic kidney disease, which should be taken into account in future therapeutic approaches.

This study investigates the role of autophagy-related genes (ARGs) in bladder cancer (BLCA), focusing on the regulator of G protein signaling 19 (RGS19). Using data from The Cancer Genome Atlas (TCGA) and the Human Autophagy Database (HADb), we identified RGS19 as significantly upregulated and linked to poor prognosis in BLCA. Kaplan-Meier survival analysis confirmed its association with increased mortality and. In vitro, RGS19 knockdown in BLCA cell lines inhibited proliferation, migration, and invasion, while inducing apoptosis and autophagy. Transmission electron microscopy showed autophagic structures in RGS19-silenced cells. In vivo, a xenograft mouse model demonstrated reduced tumor growth with RGS19 knockdown. Immunohistochemical (IHC) analysis revealed decreased Ki67 and increased autophagy markers in tumors with reduced RGS19. Pathway analysis suggested RGS19 acts through the cGMP-PKG signaling pathway, validated by altered expression of soluble guanylate cyclase (sGC), protein kinase G (PKG1), phosphodiesterase 5 A (PDE5A), vasodilator-stimulated phosphoprotein (VASP), and phosphorylated VASP (p-VASP) upon RGS19 knockdown. These results highlight RGS19 as a potential biomarker and therapeutic target in BLCA.

Neuronal splicing regulator RNA binding protein, fox-1 homolog 3 (NeuN/RbFox3), is expressed in postmitotic neurons and distributed heterogeneously in the cell. During excitotoxicity events caused by the excess glutamate, several alterations that culminate in neuronal death have been described. However, NeuN/RbFox3 organization and distribution are still unknown. Therefore, our objective was to analyze the nucleocytoplasmic distribution and organization of NeuN/RbFox3 in hippocampal and cortical neurons using an excitotoxicity model with monosodium glutamate salt (MSG). We used neonatal Wistar rats administered subcutaneously with 4 MSG mg/kg during the postnatal day (PND) 1, 3, 5, and 7. The control group was rats without MSG administration. On 14 PND, the brain was removed, and coronal sections were used for immunodetection with the antibody NeuN, DAPI, and the propidium iodide staining for histological evaluation. The results indicate that in the control group, NeuN/RbFox3 was organized into macromolecular condensates inside and outside the nucleus, forming defined nuclear compartments. Additionally, NeuN/RbFox3 was distributed proximal to the nucleus in the cytoplasm. In contrast, in the group treated with MSG, the distribution was diffuse and dispersed in the nucleus and cytoplasm without the formation of compartments in the nucleus. Our findings, which highlight the significant impact of MSG administration in the neonatal period on the distribution and organization of NeuN/RbFox3 of neurons in the hippocampus and cerebral cortex, offer a new perspective to investigate MSG alterations in the developmental brain.

Fluoride affects neurodevelopment in children. In this study, we examined the effects of developmental exposure to sodium fluoride (NaF) on hippocampal neurogenesis in rats. Dams were given drinking water containing NaF at 0 (untreated controls), 30 or 100 ppm from gestational day 6 to day 21 post-delivery upon weaning, and offspring were reared until postnatal day (PND) 77. On PND 21, NaF at 100 ppm altered the numbers in subpopulations of granule cell lineages, including a decrease in type-3 neural progenitor cells (NPCs), as well as a compensatory increase in type-1 neural stem cells (NSCs) and type-2a NPCs. NaF exposure tended to increase GluR2 mossy cells in the hilus of the dentate gyrus (DG) in a dose-dependent manner, suggesting that NaF exposure induces a compensatory neurogenic response. NaF also caused a dose-dependent increase in ARC granule cells, and it upregulated Ptgs2 in the DG at 100 ppm, suggesting that NaF exposure increases synaptic plasticity in granule cells. NaF at 100 ppm upregulated granule cell lineage marker genes (Nes, Eomes and Rbfox3) and an anti-apoptotic gene (Bcl2), suggesting ameliorating responses against the impaired neurogenesis during NaF exposure. Moreover, NaF at 100 ppm downregulated oxidative phosphorylation-related genes (Atp5f1b and Sdhd) and upregulated a glycolysis-related gene (Hk3), suggesting a metabolic shift in cells undergoing neurogenesis. By PND 77, the changes in granule cell lineages were no longer detected, and GABAergic interneuron marker genes (Calb2 and Reln) were upregulated, suggesting a persistent protective response in granule cell lineages. Together, these findings suggest that developmental NaF exposure causes transient disruption of hippocampal neurogenesis, which in turn induces a metabolic shift as a compensatory response.

The elastic system is one of the most developed interstitial elements in connective tissue. With diverse functions, pre-elastic and elastic fibers contribute to the distensibility and malleability of several organs. Also, microanalyses of the elastic system were obtained by different histological techniques that were employed over years to describe normal and pathological conditions. Compared to conventional stains, hematoxylin-eosin/phloxine (HE/P) under fluorescence and confocal microscopy presented a highly detailed observation of the elastic system in different organs and scenarios. This technique provides a better demarcation of the elastic fibers, favoring their description in relation to their deposition and aggregation in different organs. Also, fibrils with low aggregation or loss of this characteristic are observed in an optimal view in the skin, heart valves, and large-caliber blood vessels. Degradation, fragmentation, and rupture were also well described by the HE/P technique. Several organs, such as the mammary gland, prostate, skin, aorta, and lung, could be described with precision under this technique. In association with non-linear microscopy, the results of the research presented in this paper improved and detailed characteristics of precise pathogenesis. Thus, the HE/P technique presented an interesting efficiency to demonstrate alterations and structures in which the elastic system showed a relevant role, and when compared to other techniques it demonstrated a similar or better result. In addition, it is expected that future studies can reveal more information about the elastin and interactions with specific dyes, thus allowing a greater understanding of the great efficiency of this technique.

This scoping review aimed to characterize the histological changes in skeletal muscle after heart failure (HF) and to identify gaps in knowledge.

To date, no report has compared section thickness (ST) between the sliding microtome (SM) and rotary microtome (RM). We used the ice pack (IP) condition, in which the paraffin block was not cooled during slicing, and a continuous cooling device (CCD) for continuous cooling during slicing. The ST was greater for the SM than the RM in the IP condition, but it was identical between the devices under the CCD condition. Thus, we used the CCD condition for subsequent studies. In formalin-fixed, paraffin-embedded (FFPE) fish sausage blocks, the ST of the tissue surface (T-surface) was significantly concaved compared to that of the paraffin surface (P-surface) for both microtomes. On the contrary, in FFPE human kidney blocks, ST did not differ between the T-surface and P-surface. Furthermore, the eosin-positive area of PAM-stained specimens was affected by ST, and the color tone of the thickest sample differed from that of the median or thinnest sample. Our data indicated that we should use CCD conditions to ensure that ST is uniform regardless of the type of microtome. In addition, for quantitative analysis, we should utilize ST measure equipment and specimens with a constant ST.

Severe acute pancreatitis (SAP) is a common digestive system disorder in clinical practice, and it is often associated with liver damage in patients with severe acute pancreatitis. Several studies have indicated that pyroptosis plays a role in liver damage following severe acute pancreatitis (SAP). However, the precise mechanisms remain unclear. This study aims to elucidate the association and specific mechanisms between liver injury following SAP and pyroptosis, providing theoretical support for research on SAP-induced liver injury.

An electron microscopy and immunohistochemistry study has been conducted to acquire comparative information on the structure of apteric skin in ratites, ostrich and emu. The epidermis is thin in the neck of both species and thicker in the dorsal region where acidic and neutral keratins are present in the viable epidermis and stratum corneum. The dermis in both species is mostly occupied by collagen fibrils that form large bundles, often organized in alternated layers in the deeper part of the dermis. Numerous collagen fibrils contact the basement membrane of the epidermis. Sparse tactile Meissner or Krause sensilli are present among the thick collagen bundles. The ostrich epidermis in the dorsal skin is thicker than in the neck, with a columnar basal layer, 3-5 intermediate suprabasal layers and a thick corneous layer. The epidermis of the neck in emu is very thin, featuring two-three narrow cell layers above a flat basal layer and a relatively thick corneous layer. Basal and suprabasal keratinocytes contain lipid droplets and small keratin bundles but no keratohyalin accumulates in pre-corneous cells. The thin corneocytes form a multilayered corneous layer. Loricrine is present in pre-corneous and corneous layers while CBPs, formerly indicated as beta-keratins, are absent in apteric epidermis.

Bone marrow biopsy depends on tissue morphology, immunohistochemical staining, and moleculardetection. Tissue pretreatment is required for bone marrow samples, from clinical specimen acquisition to pathological reporting, but during the process, proteins and nucleic acids are often altered because of the acid in fixation and decalcification solutions. In our study, we present an easy and effective pretreatment protocol and compared this novel pretreatment protocol (Set 2) with an existing traditional pretreatment process (Set 1) using tissue morphology, IHC staining, and molecular pathological analyses. Granulocytic IHC markers showed more intensive staining in samples of Set 2 than in those of Set 1. The Set 2 protocol provided a higher DNA yield and less fragmentation; moreover, samples processed with the Set 2 protocol could be subsequently used in FISH and DNA sequencing assays. Our optimized novel pretreatment protocol could better protect proteins and DNA molecules while maintaining good cell morphology compared to traditional pretreatment The novel pretreatment reagents could role as a reference by more laboratories for pretreating bone marrow biopsy samples and scientific research.

The carotid body is a hypoxia-sensitive chemoreceptor that induces sensory long-term facilitation after exposure to chronic intermittent hypoxia. However, the mechanisms underlying synaptic plasticity in the carotid body remain unknown. In the present study, we examined the immunohistochemical distribution of cannabinoid receptor type 1 (CB1) and type 2 (CB2), which are candidate molecules involved in the modulation of synaptic transmission. Dot-like CB1 immunoreactivity was distributed in the perinuclear cytoplasm of chemoreceptor cells immunoreactive for the catecholamine-synthesizing enzymes, tyrosine hydroxylase and dopamine beta-hydroxylase. Furthermore, CB1 immunoreactivity was observed in sensory nerve endings immunoreactive for P2X purinoceptors that colocalized with vesicular glutamate transporter 2. On the other hand, immunoreactivity for CB2 was mainly distributed in chemoreceptor cells, and was weakly observed in sensory nerve endings immunoreactive for P2X purinoceptors. The present results suggest that CB1 and CB2 regulate the release of catecholamines and glutamate from chemoreceptor cells and sensory nerve endings, respectively. Therefore, CB1 and CB2 may be involved in synaptic plasticity in the carotid body.

Membrane trafficking and actin-remodeling are critical for well-maintained integrity of the cell organization and activity, and they require Arf6 (ADP ribosylation factor 6) activated by GEF (guanine nucleotide exchange factor) including EFA6 (exchange factor for Arf6). In the present immuno-electron microscopic study following previous immunohistochemical study by these authors (Chomphoo et al., 2020) of in situ skeletal myoblasts and myotubes of pre-and perinatal mice, the immunoreactivity for EFA6A was found to be localized at Z-bands and sarcoplasmic reticulum (SR) membranes in I-domains as well as I-domain myofilaments of skeletal myofibers of perinatal mice. Based on the previous finding that EFA6 anchored on the neuronal postsynaptic density via α-actinin which is known to be shared by muscular Z-bands, the present finding suggests that EFA6A is also anchored on Z-bands via α-actinin and involved in the membrane trafficking and actin-remodeling in skeletal myofibers. The localization of EFA6A-immunoreactivity in I-domain SR suggests a differential function in the membrane traffic between the I- and A-domain intracellular membranes in perinatal skeletal myofibers.

Cutaneous melanoma (cM) is a prevalent invasive cancer resulting from the malignant transformation of melanocytes. At present, the primary treatment for melanoma is surgical resection, which is not appropriate for patients with metastasis. Therefore, it is necessary to identify effective therapeutic targets for the early diagnosis and treatment of metastatic melanoma. Acyl-CoA thioesterase 7 (ACOT7) has been reported to be involved in the progression of multiple cancer, while its role in melanoma has not been extensively researched. Through gain-of-function and loss-of-function experiments, ACOT7 was identified as a tumor promoter that facilitates the progression of melanoma cells. Cell proliferation was promoted by overexpressing ACOT7 in M14 cells, and was suppressed by silencing ACOT7 in MeWo cells. Knockdown of ACOT7 induced cell cycle arrest by increasing the expressions of cyclin dependent kinase inhibitor 1B (P27) and cyclin dependent kinase inhibitor 1 A (P21), while simultaneously reducing proliferating cell nuclear antigen (PCNA) expression. Upregulation of ACOT7 promoted the cell cycle of melanoma cells. Additionally, apoptosis was induced by the absence of ACOT7 through activating caspase-3 and poly (ADP-ribose) polymerase (PARP). The metastatic and invasive capacity of melanoma cells was significantly enhanced by the overexpression of ACOT7 and inhibited by the downregulation of ACOT7. Moreover, the cAMP responsive element binding protein 1 (CREB1) positively regulates ACOT7 expression by binding to its promoter region. A decrease of cell proliferation, migration and invasion, as well as an increase of cell apoptosis induced by silencing CREB1 were obviously reversed by ACOT7. In summary, ACOT7 transcriptionally activated by CREB1 elevates the progression of cM.

Our previous study has shown that exosomes derived from human umbilical cord mesenchymal stem cells (hUCMSCs-exo) alleviated burn-induced acute lung injury (ALI). In this study, we explored a novel mechanism by which hUCMSCs-exo contributed to the inhibition of burn-induced ALI. The ALI rat model with severe burn was established for the in vivo experiments, and rats PMVECs were stimulated with the serum from burn-induced ALI rats for the in vitro experiments. The pathological changes of lung tissues were evaluated by HE staining; the cell viability was measured using CCK-8; the iron level and Fe concentration were assessed using Iron Assay Kit and Fe fluorescence detection probe; the mRNA expression of SLC7A11 and GPX4 were measured by qRT-PCR; the protein levels of SLC7A11, GPX4, Nrf2 and HO-1 were detected by western blot. Both the in vivo and in vitro experiments revealed that ferroptosis was significantly induced in burn-induced ALI, which as verified by increased iron level and Fe concentration, and decreased SLC7A11 and GPX4 mRNA and protein levels. Furthermore, both hUCMSCs-exo and Fer-1 (the inhibitor of ferroptosis) alleviated lung inflammation and up-regulated protein levels of Nrf2 and HO-1 in the lung tissues of burn-induced ALI rats. These results suggested that hUCMSCs-exo exhibited a protective role against burn-induced ALI by inhibiting ferroptosis, partly owing to the activation of Nrf2/HO-1 pathway, thus providing a novel therapeutic strategy for burn-induced ALI.

Esophageal cancer is one of the most common malignant tumors in the world. It is urgent to prevent the development and progression of esophageal cancer. Cancer stem cells (CSCs) were reported to have the ability to initiate tumorigenesis, and reducing the stem cell-like characteristics of tumors is an important strategy to inhibit the occurrence and development of tumors. miRNAs are key regulators of the stemness of cancer. Here, we aimed to investigate the role and regulatory mechanism of miR-191-3p in the stemness properties of esophageal cancer cells.

Tumour endothelial cells (TECs) are genetically and phenotypically distinct from their normal, healthy counterparts and provide various pro-tumourigenic effects. This study aimed to investigate the impact of conditioned media (CM) from non-tumourigenic MCF-12A breast epithelial cells as well as from MCF-7 and MDA-MB-231 breast cancer cells on human umbilical vein endothelial cells (HUVECs). Significant increases in cell viability were observed across all breast CM groups compared to controls, with notable differences between the MCF-12A, MCF-7, and MDA-MB-231 groups. Despite increased viability, no significant differences in MCM2 expression, a marker of cell proliferation, were detected. Morphological changes in HUVECs, including elongation, lumen formation, and branching, were more pronounced in breast cancer CM groups, especially in the MDA-MB-231 CM group. qPCR and Western blot analyses showed increased expression of TEC markers such as MDR1, LOX, and TEM8 in HUVECs treated with MCF-12A CM. The MCF-7 CM group significantly enhanced HUVEC migratory activity compared to MCF-12A CM, as evidenced by a scratch assay. These findings underscore distinct angiogenic responses elicited by non-tumourigenic and tumourigenic breast epithelial cells, with tumourigenic cells inducing a hyperactivated angiogenic response. The study highlights the differential effects of breast cancer cell paracrine signalling on endothelial cells and suggests the need for further investigation into TEC markers' role in both physiological and tumour angiogenesis.