Journal of Molecular Histology最新文献

A poorer prognosis is thought to be associated with “double expressor lymphomas,” which are a subtype of diffuse large B cell lymphomas (DLBCL) that co-express MYC and BCL2. While the role of ubiquitin-specific peptidase 37 (USP37) in lung cancer, where it mediates the deubiquitination and stabilization of c-myc, has been well-documented, its involvement in DLBCL remains unexplored. The use of RT-PCR, immunohistochemistry, or WB test allowed for the detection of elevated USP37 in DLBCL tissues and cells. In order to understand the function of USP37 in DLBCL, keloid DLBCL cells were transfected with si-USP37 using Lipofectamine 3000. When tested on DLBCL cells, USP37 increased cell proliferation and inhibited cell cycle progression. USP37 controls the process of deubiquitination to stabilise c-myc proteins. The overexpression of c-Myc facilitated cell proliferation and prevented the cell cycle of DLBCL cells stimulated by si-USP37, which should be taken into consideration. Furthermore, USP37 depletion consistently hinders the development of tumour xenografts in mouse models. Overexpressing c-myc, however, may partially counteract this impact. The data show that USP37 may be a potential therapeutic target for DLBCL, and that it may enhance the course of the disease by deubiquitinating c-myc via direct interactions with c-myc.

The purpose of this study was to explore the inhibitory effect of andrographolide on the expression of key regulatory genes involved in the biofilm formation of Staphylococcus epidermidis (SE). Taking the film-producing strain Staphylococcus epidermidis SE1457 as the research object, the effect of andrographolide on the formation of Staphylococcus epidermidis biofilms was analyzed via crystal violet staining, and biofilm models of SE adhesion, aggregation and maturity were established in vitro. RT‒PCR was used to detect the effects of the expression of icaA-, atlE-, aap- and luxS-related genes of andrographolide on biofilm formation in SE. Congo red qualitative test to evaluate the ability of andrographolide to inhibit biofilm formation of Staphylococcus epidermidis. Compared with that of the control group, the light absorption value of the low- and high-concentration andrographolide groups was significantly lower, and the light absorption value of the high-concentration andrographolide group was significantly lower than that of the low-concentration andrographolide group. The levels of key genes involved in the adhesion, aggregation and maturation of icaA, atlE, aap and luxS in group C were greater than those in group B. The biofilm-forming ability of SE in group A was strong, and the colonies were obviously black. The colony in the direction of the arrow in group B was red, and the SE biofilm was inhibited. Most of the colonies in group C were red. SE biofilms were significantly inhibited. Andrographolide inhibits SE biofilm formation, and its mechanism may involve inhibition of the expression of the related genes icaA, atlE, aap and luxS.

Ki-67 is a histological marker indicating cancer aggressiveness, while tryptophan (TRP) depletion modulates immune responses, including tumor aggressiveness. The study evaluates Ki-67's predictive value in relation to plasma TRP levels in invasive ductal carcinoma of breast cancer, aiming to improve understanding of tumor characteristics and clinical behavior. A study involving 165 women, measured plasma TRP levels and Ki-67 and analyzed their relationship with tumor aggressiveness markers using statistical analyses and predictive models. Our study highlighted a significant correlation between decreased plasma levels of TRP and a high mitotic index, measured by the Ki-67 marker (Pearson correlation coefficient r = − 0.402; p = 0.011). Tryptophan levels below 40 µmol/L were associated with a Ki-67 level above 15%, suggesting more active tumor growth in patients. Additionally, several risk factors for BC were identified within the studied population. The demographic and clinical characteristics of the participants include an average age of 63 years, plasma glucose levels above 1.2 g/L, and plasma TRP levels below 40 µmol/L, which are associated with an increased risk of BC. Furthermore, various polynomial logistic regression models indicate that TRP levels may be predicted based on Ki-67 expression, providing a promising approach to refine prognostic assessments. The study showed a correlation between low levels of tryptophan (TRP) and a high Ki-67 mitotic index in breast cancer patients, particularly in invasive ductal carcinoma, which is strongly linked to the aggressiveness of the disease. The integration of these markers into routine practice remains a technical and economic challenge.

Aging is a worldwide socioeconomic burden. Cerebellar aging is an enigma contributing to many behavioral aging disorders, hence is its hindering by prophylactic measurements is a crucial geriatric research target. Red dragon fruit (RDF) is a tropical fruit with antioxidant, anti-inflammatory and anti-apoptotic properties. This study aimed to determine the protective effect of RDF extract against cerebellar aging. Thirty-two male albino rats were randomly allocated into 4 groups: Control, RDF, aged and RDF-aged groups. Aged group revealed structural distortion affecting cerebellar layers including a significant (P < 0.05) decrease in Purkinje cells number and decrease in granular cell layer thickness by comparison to the control and RDF groups. Additionally, distorted capillary endothelium, and defective myelination were noticed. Interestingly, cerebellar active caspase-3, iNOS, MDA and 3-NT and serum TNF-α levels significantly increased with aging by comparison to the control and RDF groups (all P < 0.05). Biochemical analysis revealed a significant (P < 0.05) decrease in cerebellar SOD and serum GSH levels in aged rats. RDF extract remarkably ameliorated most of the neuronal degenerative changes with a significant (P < 0.05) increase in Purkinje cells numbers, and granular cell layer thickness by comparison to the aged group. Furthermore, it resulted in a significant (P < 0.05) decrease in cerebellum expression of active caspase-3, iNOS, MDA, 3-NT, and serum TNF-α levels associated with a significant (P < 0.05) increase in cerebellar SOD and serum GSH levels by comparison to the aged group. To the best of our knowledge this is the first study showing a neuroprotective effect for RDF against cerebellar aging. RDF might be effective in attenuation of age-induced cerebellar degenerative changes through its anti-apoptotic, antioxidant and anti-inflammatory effects.

Traditional antidiabetic treatments often carry the risk of beta-cell exhaustion, highlighting the need for therapies that promote beta-cell regeneration. This study investigates the comparative effects of Liraglutide, naltrexone/bupropion (NTX + BUP), and caloric restriction on metabolic control and beta-cell regeneration in a rat model of obese type 2 diabetes. Fifty male albino rats were randomized into five groups: normal control, diabetic control, diabetic + caloric restriction (50%), diabetic + NTX + BUP (4 mg/45 mg /kg/day orally), and diabetic + liraglutide (0.3 mg/kg/day, S.C). Body weight, BMI, serum glucose, insulin, lipid profile, atherogenic indices, beta-arrestin-1 levels, pancreatic histopathology, and immunohistochemical staining for insulin and Ki67 were assessed. All interventions significantly improved body weight, BMI, glycemic control, lipid profiles (except HDL), and atherogenic indices compared to the diabetic control group. NTX + BUP and caloric restriction resulted in greater weight loss compared to liraglutide. Of note, liraglutide significantly decreased β-arrestin-1 levels compared to both NTX + BUP and caloric restriction. Furthermore, liraglutide and caloric restriction significantly increased anti-insulin antibodies and Ki67 indicating beta-cell regeneration, while NTX + BUP showed insignificant effects. Thus we can conclude that, while NTX + BUP demonstrates efficacy in improving metabolic parameters in obese type 2 diabetic rats, it shows limitations in promoting beta-cell regeneration compared to liraglutide and caloric restriction.

Cyclophosphamide (CP) is widely used in chemotherapy to treat various types of cancer. However, it is toxic to the liver and other organs. Rosmarinic acid (RA) possesses anti-inflammatory, antioxidant, and cytoprotective properties. This study investigated the protective effects of RA against CP-induced liver injury in mice. Mice were treated with RA (25, 50, and 100 mg/kg) for 15 days and followed by a single injection of CP on day 16th. CP injection resulted in an elevation in serum AST, ALT, and ALP, along with multiple histopathological alterations in the liver. CP also induced increased levels of MDA and NO, associated with declined GSH, SOD and CAT. RA pretreatment prevented liver injury, alleviated the enhanced levels of MDA and NO, and restored antioxidants defenses, hence avoiding the oxidative injury in the liver. Moreover, RA pretreatment attenuated NF-κB p65 and proinflammatory cytokines levels. Liver of CP-injected mice also showed a decrease in Bcl2, accompanied with elevated BAX and caspase-3 expression, an effect that RA pretreatment alleviated. In addition, pretreatment of CP-administrated mice with RA restored the Nrf2 expression in the liver. Taken together, this study suggests a potential application value of RA in preventing CP hepatotoxicity and sheds light on the possible mechanism.

Graphical abstract

Schematic diagram summarizing the hepatoprotective role of RA in a mouse model of CP hepatotoxicity. RA restored cellular redox status, suppressed inflammatory response, mitigated apoptosis, and upregulated Nrf2 pathway in the liver of CP-injected mice. CP cyclophosphamide, RA rosmarinic acid

Fish may have different sensitivity to pollutants present in the water. We analyzed the liver histology, and P-gp expression in six species of fish from the Doce River basin. Fish were caught at six different points in the Doce River, and liver samples were taken for histological analysis. P-gp expression was analyzed using an immunohistochemical technique. In Astyanax lacustris, Hoplias intermedius, Hypostomus affinis, Trachelyopterus striatulus and Oligosarcus acutirostris, a double arrangement of hepatocyte plates was generally observed (tubular-form), while in Deutorodon taeniatus, a single arrangement of hepatocyte plates was frequently observed (cord-like). Histological changes, such as cytoplasmic vacuolation and nuclear alteration, were observed in the livers of all species analyzed, however, the species A. lacustris (34.1%) and H. affinis (33.3%) were those with the fewest individuals with histological changes. The H. intermedius, T. striatulus, and O. acutirostris were the species that presented more than 80% of their individuals with histological changes. The A. lacustris and H. affinis were the species that showed the highest P-pg immunolabeling in the liver, while the T. striatulus and O. acutirostris had the lowest levels. These results support the hypothesis that levels of P-gp expression could respond to the resistance or sensitivity of each species to environmental pollutants.

When a lower limb is injured, the most delicate organs that are at risk of harm are the lungs. Among the flavonoids, quercetin is a significant component that is found in apples and onions in the highest proportions. Numerous biological actions, including as anti-inflammatory, antioxidant, and anti-cancer properties, have been linked to quercetin. To investigate the impact of quercetin on lung injury induced by skeletal muscle ischemia reperfusion (IR) injury. Three equal groups of twenty-four adult rats were used: control, Ischemia-reperfusion (IR) group and IR group treated with quercetin. Rats in (IR) group were exposed to ischemia by ligation of femoral artery for 2h then after removal of the clamp, reperfusion was estabilished for another 24h. IR group treated with quercetin, rats were underwent hind limb IR as described in group II then were given quercetin that was administered at a dose of 20mg/kg intraperitoneally. Measurement of cytokines in serum, MDA in tissue homogenate and VEGF in serum and tissue homogrnate in addition to mRNA expression level and detection of protein level of both sirtuin-1(SIRT1) and NF-κB were assessed at the end of experiment. Histological and immunohistochemical assessment of the lungs were also carried. IR group showed notable rise of inflammatory cytokines such as IL-1β, IL-6 and TNF-α in addition to high level of VEGF and MDA in IR group when compared to the IR group treated with quercetin. Also, gene expression and protein level of SIRT1 were reduced while NF-κB mRNA expression and protein level were significantly upregulated in IR group compared to IR group treated with quercetin. Histologically, IR group indicated marked histological alterations of lung tissue. Also, IR showed strong brownish cytoplasmic immunostaining for iNOS and abundance of Ki67-positive cells. These alterations were significantly reversed in IR group treated with quercetin. Biochemical and immunohistochemical findings of this study demonstrate that quercetin administration have protective effects against lung injury induced by lower limb IR.

Diabetic nephropathy (DN) is one of the most relevant and prevalent microvascular complications associated with Diabetes Mellitus. In recent years, hyperbaric oxygen therapy (HBO) has been used to mitigate tissue damage caused by hypoxia, thereby attenuating inflammatory processes. This study aimed to explore morphological aspects associated with DN in rats subjected to HBO. Forty-eight Wistar rats were divided into the following groups: C (normoglycemic animals), n = 12; C + HBO (normoglycemic animals submitted to HBO), n = 12; D (diabetic animals) n = 12; D + HBO (diabetic animals submitted to HBO), n = 12. The C + HBO and D + HBO groups were daily treated with HBO at 2.5 atmospheres absolute pressure (ATA) for 60 min, 5 days a week, for 5 weeks. Kidneys were collected for assessment of structural changes in the tissue parenchyma, assessment of renal fibrosis and renal protein expression of tumor necrosis factor-α (TNF-α) and transforming growth factor-β1 (TGF-β1). Our results showed that group D had hyperglycemia and weight loss, and that there was also an increase in the renal corpuscle, Bowman’s space, and distal tubular epithelium, as well as accumulation of collagen. HBO administration effectively prevented glomerular hypertrophy and attenuated the expression of TNF-α and TGF-β1. It also positively affected renal tubules, inhibiting the development of tubular atrophy. These findings suggest that HBO was effective in attenuating the initial alterations observed in DN.

Graphical Abstract

Pancreatic development is a complex process vital for maintaining metabolic balance, requiring intricate interactions among different cell types and signaling pathways. Fibroblast growth factor receptors 2b (FGFR2b)-ligands signaling from adjacent mesenchymal cells is crucial in initiating pancreatic development and differentiating exocrine and endocrine cells through a paracrine mechanism. However, the precise critical time window that affects pancreatic development remains unclear. To explore the roles of FGFR2b-ligands and identify the narrow window of time during which FGFR2b-ligand signaling affects pancreatic development, we used an inducible mouse model to control the expression of soluble dominant-negative FGFR2b (sFGFR2b) at various stages of pancreatic development. Our findings revealed a significant effect of FGFR2b-ligand signaling on epithelial morphology, lumen formation, and pancreatic branching during primary and secondary transition stages. Additionally, sFGFR2b expression reduced the number of Pdx1+ progenitor cells and altered the pancreatic islet structure. Furthermore, we examined the effect of mutation in FGF10, an FGFR2b ligand, on embryonic pancreatic β-cell function. FGF10 null mutant embryos exhibited reduced pancreatic size and a decrease number of islet-like structure. Although neonatal mice with haploinsufficiency for FGF10 exhibited abnormal glucose tolerance test results, indicating a potential diabetes predisposition, these abnormalities normalized with age, aligning with observations in wild type mice. Our study underscores the critical role of FGFR2b-ligand signaling in pancreatic development and postnatal islet function, offering insights into potential therapeutic targets for pancreatic disorders.