Acta Histochem. [JOURNAL]
Sun
200 papers
Targeting TEAD would be a potential strategy for scarless wound repair: A preliminary study.
Yang MY, Quan HY, Li DL … +2 more , Ruan J, Fan HY
Acta Histochem · 2025 Mar · PMID 39667304 · Publisher ↗
Despite of decades of efforts, novel approaches are still limited to attenuate or prevent skin scarring. A previous report published in Science demonstrated that inhibition of YAP promotes scarless wound repair by regene...
Despite of decades of efforts, novel approaches are still limited to attenuate or prevent skin scarring. A previous report published in Science demonstrated that inhibition of YAP promotes scarless wound repair by regeneration. Due to the difficult drugability of targeting YAP, we speculated that inhibition of TEAD, a partner molecule of YAP, might exist similar therapeutic potential. Therefore, the aim of the study was to evaluate therapeutical effect of a novel inhibitor of TEAD auto-palmitoylation, VT107, on scar formation in a cutaneous wound healing model. Our findings confirmed VT107 exhibited favorable effect on preventing scarring, manifesting as reducing fibroblast proliferation and collagen denaturation, decreasing TGF-β1 and collagen deposition, as well as connective tissue growth factor (CTGF) expression. These findings provide a novel insight for the development of anti-scarring strategies. TEAD would become an ideal target for the treatment of scars.
Autophagy markers expression pattern in developing liver of the yotari (dab1) mice and humans.
Dražić Maras E, Kelam N, Racetin A … +6 more , Haque E, Dražić M, Vukojević K, Katsuyama Y, Saraga-Babić M, Filipović N
Acta Histochem · 2025 Mar · PMID 39647211 · Publisher ↗
Autophagy plays an important role in the physiology and pathology of the liver. Several negative autophagy regulators have been discovered, including epidermal growth factor receptor (EGFR), mediated by activation of the...
Autophagy plays an important role in the physiology and pathology of the liver. Several negative autophagy regulators have been discovered, including epidermal growth factor receptor (EGFR), mediated by activation of the PI3K/Akt/mTOR signaling pathway. Disabled-1 (Dab1) is one of the mediating adaptor factors of PI3K/Akt/mTOR signaling pathways. We investigated the potential impact of Dab1 on autophagy-related markers (LC3B, LAMP2A, HSC70, and GRP78) in the developing liver by using a model of yotari mice and compared it with autophagy marker expression in human liver development. Mouse embryos were obtained at gestation days 13.5 and 15.5 (E13.5 and E15.5), and a total of 5 normal human conceptuses were obtained between gestation days 5 and 10. Histological sections were analyzed by immunohistochemistry. The highest expression of the early endosome-forming factor LC3B and the microautophagy factor LAMP2a was observed at the transition from embryonic to early fetal phase, whereas the expression of the chaperones HSC 70 and GRP78 was highest at embryonic phase. The expression patterns of three of these factors in mouse liver were different from those in human liver: the expression of LC3B was high at E13.5, that of HSC 70 at 15.5, whereas the expression of GRP78 did not change significantly. On the other hand, the expression pattern of LAMP2a was similar to that in human development and was higher at E15.5 than at E13.5. Moreover, knockout of Dab1 resulted in significantly lower expression of LC3B and LAMP2a in mouse embryo livers (at E13.5), indicating a possible role of Dab1 in regulating autophagy during embryonic development in the liver.
Molecular signature-based labeling techniques for vascular endothelial cells.
Dobariya KH, Goyal D, Kumar H
Acta Histochem · 2025 Mar · PMID 39644518 · Publisher ↗
Vascular endothelial cells (VECs) play a crucial role in the development and maintenance of vascular biology specific to the tissue types. Molecular signature-based labeling and imaging of VECs help researchers understan...
Vascular endothelial cells (VECs) play a crucial role in the development and maintenance of vascular biology specific to the tissue types. Molecular signature-based labeling and imaging of VECs help researchers understand potential mechanisms linking VECs to disease pathology, serving as valuable biomarkers in clinical settings and trials. Labeling techniques involve selectively tagging or marking VECs for visualization. Immunolabeled employs antibodies that specifically bind to VECs markers, while fluorescent tracers or dyes can directly label VECs for imaging. Some techniques use specific carbohydrate residues on cell surface, while others employ endothelial-specific promoters to express fluorescent proteins. Additionally, VEC can be labeled with contrast agents, radiolabeled tracers, and nanoparticles. The choice of labeling technique depends on study context, including whether it involves animal models, in vitro cell cultures, or clinical applications. Herein, we discussed the various labeling methods utilized to label VECs and the techniques to visualize them.
Corrigendum to "MicroRNA-146b-5p suppresses cholangiocarcinoma cells by targeting TRAF6 and modulating p53 translocation" [Acta Histochem. (2021) 123 7 151793].
Ren Y, Wang X, Ji T … +1 more , Cai X
Acta Histochem · 2024 Dec · PMID 39523158 · Publisher ↗
Abstract loading — click title to view on PubMed.
Exploring the oncogenic role of RGS19 in bladder cancer progression and prognosis.
Yan L, Luo G, Han C … +2 more , Meng J, Liang C
Acta Histochem · 2024 Dec · PMID 39481225 · Publisher ↗
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 Autop...
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.
Ultrastructure and immunohistochemistry of apteric skin in ratites and its epidermal soft cornification.
Alibardi L
Acta Histochem · 2024 Dec · PMID 39476480 · Publisher ↗
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...
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.
miR-103-3p attenuates liver injury with severe acute pancreatitis by inhibiting pyroptosis through miR-103-3p/NLRP1 axis.
Zhang W, Du M, Jiang Y … +3 more , Wang J, Yu Y, Zhang D
Acta Histochem · 2024 Dec · PMID 39476479 · Publisher ↗
BACKGROUND: 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 indica...
BACKGROUND: 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. METHODS: A rat model of SAP with concomitant liver injury was successfully established. The expression levels of miR-103-3p across different liver tissue groups were quantified using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Bioinformatic analyses and dual-luciferase reporter assays confirmed that NLRP1 is a direct target of miR-103-3p. In vivo assessments of miR-103-3p levels were performed, and the extent of cell pyroptosis during liver injury post-SAP was evaluated through western blotting, qRT-PCR, scanning electron microscopy, histopathology, immunofluorescence, and immunohistochemistry. The role of miR-103-3p in regulating NLRP1-mediated pyroptosis and its impact on SAP-induced liver injury were validated. RESULTS: This study reports that following SAP-induced liver injury, the expression of miR-103-3p in liver tissue was significantly decreased, and cell pyroptosis was involved in the process of liver injury. Experimental validation indicated that NLRP1 was a downstream target of miR-103-3p. Overexpression of miR-103-3p in vitro significantly alleviated the severity of liver injury following SAP, while simultaneously inhibiting cell pyroptosis. CONCLUSION: These findings indicate that pyroptosis may be linked to SAP-induced liver injury and that miR-103-3p mitigates hepatocyte pyroptosis by reducing liver injury through the suppression of NLRP1 expression.
Section thickness is identical for the sliding microtome and rotary microtome under the continuous cooling device condition.
Fukuzawa M, Kushibiki R, Kanehira Y … +5 more , Ishizawa A, Kameda M, Kobayashi S, Nishijima Y, Saio M
Acta Histochem · 2024 Dec · PMID 39454296 · Publisher ↗
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 c...
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.
The elastic system: A review of elastin-related techniques and hematoxylin-eosin/phloxine applicability for normal and pathological tissue description.
Ruiz TFR, Ferrato LJ, de Souza LG … +3 more , Brito-Filho GE, Leonel ECR, Taboga SR
Acta Histochem · 2024 Dec · PMID 39442433 · Publisher ↗
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...
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.
Histological changes in skeletal muscle induced by heart failure in human patients and animal models: A scoping review.
Kaneguchi A, Sakitani N, Umehara T
Acta Histochem · 2024 Dec · PMID 39442432 · Publisher ↗
OBJECTIVE: This scoping review aimed to characterize the histological changes in skeletal muscle after heart failure (HF) and to identify gaps in knowledge. METHODS: On April 03, 2024, systematic searches were performed...
OBJECTIVE: This scoping review aimed to characterize the histological changes in skeletal muscle after heart failure (HF) and to identify gaps in knowledge. METHODS: On April 03, 2024, systematic searches were performed for papers in which histological analyses were conducted on skeletal muscle sampled from patients with HF or animal models of HF. Screening and data extraction were conducted by two independent authors. RESULTS AND CONCLUSION: A total of 118 papers were selected, including 33 human and 85 animal studies. Despite some disagreements among studies, some trends were observed. These trends included a slow-to-fast transition, a decrease in muscle fiber size, capillary to muscle fiber ratio, and mitochondrial activity and content, and an increase in apoptosis. These changes may contribute to the fatigability and decrease in muscle strength observed after HF. Although there were some disagreements between the results of human and animal studies, the results were generally similar. Animal models of HF will therefore be useful in elucidating the histological changes in skeletal muscle that occur in human patients with HF. Because the muscles subjected to histological analysis were mostly thigh muscles in humans and mostly lower leg muscles in animals, it remains uncertain whether changes similar to those seen in lower limb (hindlimb) muscles after HF also occur in upper limb (forelimb) muscles. The results of this review will consolidate the current knowledge on HF-induced histological changes in skeletal muscle and consequently aid in the rehabilitation of patients with HF and future studies.
Neuronal splicing regulator RBFOX3 (NeuN) distribution and organization are modified in response to monosodium glutamate in rat brain at postnatal day 14.
García Juárez AM, Carrillo González NJ, Campos-Ordoñez T … +2 more , Gasca Martínez Y, Gudiño-Cabrera G
Acta Histochem · 2024 Dec · PMID 39427608 · Publisher ↗
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...
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.
Metabolic shift as a compensatory response to impaired hippocampal neurogenesis after developmental exposure to sodium fluoride in rats.
Shobudani M, Sakamaki Y, Karasawa A … +7 more , Ojiro R, Zou X, Tang Q, Ozawa S, Jin M, Yoshida T, Shibutani M
Acta Histochem · 2024 Dec · PMID 39413662 · Publisher ↗
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...
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.
Renal expression of autophagy markers in diabetic kidney of PUFA-supplemented rats.
Brdar I, Mašek T, Racetin A … +4 more , Jurić M, Vukojević K, Bočina I, Filipović N
Acta Histochem · 2024 Dec · PMID 39405991 · Publisher ↗
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...
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.
Immunohistochemical distribution of cannabinoid receptor type 1 (CB1) and type 2 (CB2) in the rat carotid body.
Saito H, Yokoyama T, Nakamuta N … +1 more , Yamamoto Y
Acta Histochem · 2024 Dec · PMID 39405990 · Publisher ↗
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...
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.
Corrigendum to "Protective effect of FXN overexpression on ferroptosis in L-Glu-induced SH-SY5Y cells" [Acta Histochem. 126 (2024) 152135].
Wang M, Xuan T, Li H … +3 more , An J, He T, Cheng J
Acta Histochem · 2024 Dec · PMID 39343692 · Publisher ↗
Abstract loading — click title to view on PubMed.
Nrf2: A critical participant in regulation of apoptosis, ferroptosis, and autophagy in gastric cancer.
Tang L, He D, Su B
Acta Histochem · 2024 Dec · PMID 39342913 · Publisher ↗
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 invol...
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.
Early PSA-NCAM reduction in the dentate gyrus and impaired plasticity in the Alzheimer´s disease 3xTg-mice model.
Rodríguez JJ, Gardenal E, Zallo F … +2 more , Cabot J, Busquets X
Acta Histochem · 2024 Dec · PMID 39288682 · Publisher ↗
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...
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.
Maternal hyperglycemia affects cell proliferation signalling and stromal organization in the prostate of neonatal and juvenile rat offspring.
Peixoto LFF, Sudário LED, Silva MDGCE … +4 more , Mascarenhas FNADP, Muniz EH, Zanon RG, Ribeiro DL
Acta Histochem · 2024 Dec · PMID 39244868 · Publisher ↗
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...
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.
A set of pretreatment reagents including improved formula fixation and decalcification facilitating immunohistochemistry and DNA analyses of formalin-fixed paraffin-embedded bone marrow trephine biopsy.
Sun T, Xu L, Yao H … +5 more , Zhao J, Chen Z, Chen Z, Wang B, Ding W
Acta Histochem · 2024 Dec · PMID 39243590 · Publisher ↗
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...
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.
Paracrine signalling in breast cancer: Insights into the tumour endothelial phenotype.
Rass A, Eksteen C, Engelbrecht AM
Acta Histochem · 2024 Oct · PMID 39216306 · Publisher ↗
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...
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.
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