Pyknotic Research Articles

Exploring the impact of silica and silica-based nanoparticles on serological parameters, histopathology, organ toxicity, and genotoxicity in Rattus norvegicus.

Continuous exposure to nanoparticles (NPs) poses potential hazards to human health and animal life, necessitating thorough monitoring and investigation of environmental contaminants to mitigate their adverse effects. Therefore, this study investigates the histopathological alterations, serum biochemistry, oxidative stress biomarkers, and genotoxicity endpoints induced by crystalline silica (C-SiO2) NPs, sliver-silica (Ag-SiO2) and zinc-oxide silica (ZnO-SiO2) NPs in Rattus Norvegicus. Twenty-five rats were blindly distributed into groups (A, B, C, & D), with B, C, and D administered 500 µg/kg of ZnO-SiO2, Ag-SiO2, and C-SiO2 NPs intravenously (IV), while A served as the control. Severe histopathological alterations, including widening of urinary spaces, edema, necrosis of neurons, atrophy of neurons, myofibrillolysis, inflammatory exudate, disorganization of splenic cells, and pyknotic nuclei, were observed in C-SiO2 NPs-exposed rats across study organs. Compared to controls, C-SiO2 NPs significantly altered 95 % of serological, DNA damage, histopathological, and oxidative stress parameters. Ag-SiO2 and ZnO-SiO2 NPs affected 75 % and 60 % of these parameters, respectively. Among the NPs, C-SiO2 exhibited the most adverse effects. The study concludes that SiO2 coating on metal (Ag) and metal oxide (ZnO) rendered these substances biocompatible, suggesting potential applications for reducing adverse effects in living organisms. These findings also contribute to the genotoxic profiling of NPs and their potential health hazards upon exposure to humans.

Triphenyltin Influenced Carotenoid-Based Coloration in Coral Reef Fish, Amphiprion ocellaris, by Disrupting Carotenoid Metabolism.

Triphenyltin (TPT), a kind of persistent pollutant, is prevalent in the aquatic environment and could pose a threat to coral reef fish. However, little is known about the toxicity of TPT on coral reef fish, especially regarding the representative characteristics of body coloration. Therefore, this study chose the clownfish (Amphiprion ocellaris) in order to investigate the effects of TPT exposure on its carotenoid-based body coloration under the environmentally relevant concentrations (0, 1, 10 and 100 ng/L). After TPT exposure for 60 d, the carotenoid contents were decreased and histological damage in the liver was found, shown as nuclear pyknosis and shift, lipid deposition and fibrotic tissue hyperplasia. Liver transcriptomic analysis showed that TPT exposure interfered with oxidative phosphorylation and fatty acid metabolism pathways, which related to carotenoids uptake and metabolism. Furthermore, TPT exposure led to oxidative damage in the liver, which is responsible for the changes in the antioxidant capacity of enzymes, including GSH, MDA, POD, CAT and T-SOD. TPT exposure also affected the genes (Scarb1, CD36, Stard3 and Stard5) related to carotenoid absorption and transport, as well as the genes (GstP1 and Bco2) related to carotenoid deposition and decomposition. Taken together, our results demonstrate that TPT influenced carotenoid-based coloration in coral reef fish by disrupting carotenoid metabolism, which complements the ecotoxicological effects and toxic mechanisms of TPT and provides data for the body color biology of coral reef fishes.

Clear cell renal cell carcinoma with syncytial giant cells: Not that rare

Syncytial giant cells (SGCs) are neoplastic giant cells of epithelial origin. The nuclear morphology of SGCs is uniform and similar to those of adjacent mononuclear tumor cells. Clear cell renal cell carcinoma (ccRCC) with SGCs is a rare microscopic morphology. In this study, the clinical and pathological data of 16 ccRCC cases with SGCs were retrospectively reviewed. The incidence of SGCs in pathological stages pT3 and above (12.1%, 8/66) was significantly higher than that in pT1 and pT2 (2.6%, 8/306) (P = 0.002). The incidence of SGCs in the WHO/ISUP nuclear grade 3 or 4 ccRCC (12.4%, 14/113) was significantly higher than that in grade 1 or 2 (0.8%, 2/259) (P < 0.001). Two forms of SGCs were observed, some exhibited nuclear pyknosis and degeneration. Of the 16 cases, eight cases were accompanied by necrosis and seven cases had lymphovascular invasion. Both SGCs and mononuclear tumor cells were positive for ccRCC markers (PAX8, CAIX, CD10 and Vimentin). None of the SGC nuclei were positive for Ki-67. Follow-up information was available on 14 patients, with a median follow-up time of 27.5 months. Ten patients were alive without disease, three were alive with metastatic disease, and one patient died 10 months after surgery. These findings indicated that SGCs are not rare, especially in ccRCC with high nuclear grade and pathological stage, and often co-exist with other adverse prognostic features. SGCs may be senescent tumor cells, the presence of SGCs should not be considered as Fuhrman and WHO/ISUP nuclear grading 4.

PROTECTIVE EFFECTS OF GRAPE SEED EXTRACT (VITIS VINIFERA) AGAINST CISPLATIN-INDUCED LIVER DAMAGE IN RABBITS. (HISTOLOGICAL AND HISTOPATHOLOGICAL STUDY)

Cisplatin is a chemotherapeutic drug used in the treatment of various cancer types. It can be considered a double-edged sword. It is a potent anticancer agent at the same time has toxic effect on various tissues as it causes hepatotoxicity. It was determined to cause liver toxicity and to weaken the antioxidant defense systems in liver. A decrease in antioxidant enzymes resulted from cisplatin induced tissue toxicity. Moreover, the development of therapies to prevent the appearance of cisplatin- induced tissue toxicities has focused on administration of antioxidants along with cisplatin treatment. The grape seeds exhibit a broad spectrum of pharmacological properties against oxidative stress. Therefore, the aim of present study was designed to investigate the protective effects of grape seed extract on the liver damage in cisplatin treated rabbits. Twenty seven healthy rabbits of local mixed breed were selected, divided into three equal groups, the first group (CON group) served as control and received a single intraperitoneal injection of normal saline solution once per week for 6 weeks; the second group (CIS group) were treated with therapeutic dose of cisplatin intraperitoneally once per week for six weeks; the third group (CIS+GSE group) served as protective group and was concomitantly treated with grape seeds extract by oral gavages and cisplatin injection intraperitoneally once per week for six successive weeks. Administration of grape seeds extract by oral gavages starting from the first day of the experiment for 6 consecutive days before and 6 consecutive days after the cisplatin injection and continued daily for 6 weeks. The histopathological findings present in current study showed that cisplatin toxicity produced significant structural changes in the liver of CIS group, cisplatin treated group, in the form of prominent disorganized architecture and loss of liver lobulation, distortion of the arrangement of parenchyma of the liver, loss of radial arrangement of sinusoids from the central vein of the liver, Dilatation and congestion of central veins, sinusoids and portal traids, degenerative changes in hepatocytes and pyknotic nuclei indicating necrosis. Marked vacuolar degeneration mainly hydropic ballooning degeneration and hyper activation of Kupffer cells and inflammatory cellular infiltrations were also observed. This finding reflected the cytotoxic effects of cisplatin in hepatic tissue. While, in the sections from the liver of animals received therapeutic dose of cisplatin and treated by grape seed extract, group (CIS+GSE) clearly showed that there was a significant alleviated hepatotoxicity, since histopathological changes were markedly less pronounced compared to animals treated with cisplatin alone. Therefore, and based on our findings, the grape seed extract contributes significantly to the improvement of histological alterations in rabbit liver caused by cisplatin.

Integrated analysis of transcriptome, translatome and proteome reveals insights into yellow catfish (Pelteobagrus fulvidraco) brain in response to hypoxia

Brain plays a central role in adapting to environmental changes and is highly sensitive to the oxygen level. Although previous studies investigated the molecular response of brain exposure to acute hypoxia in fish, the lack of studies at the translational level hinders further understanding of the regulatory mechanism response to hypoxia from multi-omics levels. Yellow catfish (Pelteobagrus fulvidraco) is an important freshwater aquaculture species; however, hypoxia severely restricts the sustainable development of its breeding industry. In the present study, the transcriptome, translatome, and proteome were integrated to study the global landscapes of yellow catfish brain response to hypoxia. The evidently increased amount of cerebral cortical cells with oedema and pyknotic nuclei has been observed in hypoxia group of yellow catfish. A total of 2750 genes were significantly changed at the translational level. Comparative transcriptional and translational analysis suggested the HIF-1 signaling pathway, autophagy and glycolysis/gluconeogenesis were up-regulated after hypoxia exposure. KEGG enrichment of translational efficiency (TE) differential genes suggested that the lysosome and autophagy were highly enriched. Our result showed that yellow catfish tends to inhibit the TE of genes by increasing the translation of uORFs to adapt to hypoxia. Correlation analysis showed that transcriptome and translatome exhibit higher correlation. In summary, this study demonstrated that hypoxia dysregulated the cerebral function of yellow catfish at the transcriptome, translatome, and proteome, which provides a better understanding of hypoxia adaptation in teleost.

Potential Anti-Toxoplasmosis Efficiency of Phoenix dactylifera Extracts Loaded on Selenium Nanoparticles.

Toxoplasmosis is a parasitic disease caused by Toxoplasma gondii that infects humans and many types of mammals and birds. To investigate the effect of selenium nanoparticles (SeNPs) and Phoenix dactylifera (Pd) extracts loaded on SeNPs as a new agent to combat chronic T. gondii infections in murine model as an alternative method to standard Spiramycin drug therapy. A total of 64 female mice were randomly divided into eight groups: GI: Normal control, GII: Positive control, GIII: infected and treated with Spiramycin, GIV: infected and treated with SeNPs, GV: infected and treated with aqueous extract of Pd, GVI: infected and treated with methanolic extract of Pd, GVII: infected and treated with aqueous extract of Pd loaded on SeNPs, GVIII: infected and treated with methanolic extract of Pd loaded on SeNPs. Date palm (P. dactylifera) fruits were identified and collected from the farms of Saudi Arabia. Preparation and characterization of SeNPs were done. The parasitological, histopathological examinations and biochemical changes were evaluated in all groups. Parasitological results showed significant differences in GVII in comparison to GII while GVIII showed significant differences in comparison to GII and GIII. The histopathological section of the cerebral cortex showed obvious alterations in the infected compared with untreated control groups. Aqueous and methanolic extracts of P. dactylifera loaded on SeNPs treatment showed improvement that indicated by few perivascular cuffing with few inflammatory cell infiltrations. Few granule cells with mild intracellular vacuolation and edema few deformed neurons with deep pyknotic nuclei. Microglia cells expression of Iba-1 and inflammatory cytokines (IL-4, IL-10 and INF-γ) in serum of all groups was higher in GII and lowest in GVIII followed by GVII. SeNPs and P. dactylifera extracts loaded on SeNPs could be a potent agent to combat T. gondii infections.

Neuroprotective effect of Tropisetron in Streptozotocin induced animal model of Alzheimer’s disease

AbstractBackgroundAlzheimer’s disease is a neurodegenerative pathology having genetic and non‐genetic forms. Non‐genetic forms of AD dominate over the genetic condition and is mainly sporadic. However, both forms affect cognitive functions. Although exact mechanisms are not fully understood, amyloid β deposition &amp; tau tangle formation are considered central mechanisms to cause neurodegenerative changes in the AD brain. On the other hand, cognitive deterioration began way before the accumulation of amyloid or tau tangle formation. Cognitive functions, including learning and memory, have been majorly controlled/regulated by the cholinergic system. Here in the present study, we have explored the neuroprotective effect of tropisetron in streptozotocin‐induced animal model of Alzheimer’s disease. During the last two decades, the involvement of other neurotransmitter systems has been explored, and the serotonergic system has been demonstrated to play an essential role in memory and learning. The serotonergic system is the most extensive monoaminergic system in the brain, and alterations in serotonergic signals have been linked with Aβ and tau tangle formation. Moreover, serotonin acting through its receptor antagonist has been reported beneficial in various experimental AD models.MethodIn the present study animals were infused with STZ alternatively on 1st and 3rd day. From 15th day animals were treated with tropisteron with two subsequent doses (2.2.5mg/kg) and (5mg/kg). On 28th day animals were sacrificed. Further animals were tested for behavioral, biochemical and histopathological parameters.ResultTropisetron significantly attenuated oxidative damage and restored the reduced levels of anti‐oxidant enzymes. ICV‐STZ treatment had shown significant neuronal damage in hippocampal and cortical regions of AD brain in histopathological examination. Moreover, hippocampal neurons were observed to be irregular in morphology with dark pyknotic nuclei. This confirms the neurodegeneration in ICV‐STZ animals. Target drug tropisetron resulted in significant neuroprotection against ICV‐STZ.ConclusionThe observed outcomes of the present study suggest the neuroprotective effect of tropisteron in STZ induced animal model of Alzheimer’s disease.It would be safe to conclude that tropisetron may improve the behavioral outcomes by attenuating oxidative burden &amp; its neuroprotective potential as seen in our histological assessment.

A novel method for septal reduction therapy by three-dimensional guided transvenous intraseptal pulsed-field ablation

BackgroundPulsed-field ablation (PFA) is a nonthermal method for achieving selective cell death with little inflammation response. However, there are no reports of PFA for septal reduction therapy (SRT). ObjectiveThe purpose of this study was to investigate the effectiveness and safety of PFA for SRT. MethodsA novel transvenous intraseptal PFA method with 3-dimensional (3D) guidance was introduced in Yorkshire pigs. Electrocardiographic parameters, transthoracic echocardiography, and histopathology were used to evaluated. ResultsThe maximum injury diameter of intramyocardial PFA increased with electric field intensity. After PFA, bipolar electrogram amplitude and pacing threshold measured by the PFA electrodes significantly decreased (F = 6.945, P = .007) or increased (F = 5.842, P = .024), respectively. In the ablated septal region, motion amplitude and systolic wall thickening rate significantly decreased and remained at low levels (motion amplitude: F = 20.793, P = .000; systolic wall thickening rate: F = 14.343, P = .000); however, septal thickness did not significantly change after PFA (F = 1.503, P = .248). Histologic examination showed specific cardiomyocyte death with gradually increased hyperchromatic cytoplasm and nuclear pyknosis, without obvious inflammatory cell infiltration in acute phase. TUNEL stain for fragmented DNA showed extensively positive in the ablation region 24 hours after PFA. During PFA, no sustained ventricular arrhythmia or atrioventricular conduction block occurred. ConclusionA novel intraseptal PFA method with 3D guidance was described. Intraseptal PFA resulted in effective myocardial injury and local hypokinesis without significant acute edema. Histologic examination showed widely programmed cardiomyocyte death with little inflammatory cell infiltration.

Protective effect of melatonin on blood-brain barrier damage caused by Endotoxemia

ABSTRACT Objective Endotoxins, products of Gram-negative bacteria, are the primary cause of blood-brain barrier (BBB) damage. In the present study, we aimed to investigate the possible neuroprotection mechanisms of melatonin on BBB damage induced by endotoxemia. Methods Adult, female Sprague-Dawley rats (n = 42) were separated into four random groups as a control group and three treatment groups. Lipopolysaccharide (7,5 mg/kg/day) was administrated for a single dose to generate a 24-hour sepsis model on rats. Melatonin (10 mg/kg/day) was treated a week before sepsis. Afterward, the dissected brain tissues were examined by histopathological, biochemical, and molecular analyses. Results LPS caused weight loss in the groups. As a result, degenerated neurons with cytoplasmic vacuoles and irregular pyknotic nuclei, pale stained necrotic neurons, and vascular congestion were observed in LPS-exposed rats. However, MEL decreased the number of degenerated neurons in treated groups. MEL treatment increased ZO1 and Occludin immunoreactivity while decreasing TLR4 in brain tissues. MEL effect on protein expression was recorded for ZO1 increase and TLR4 decrease in brain tissue compared to LPS groups. MEL also decreased MDA levels in brain tissue. Conclusions MEL recovered the degenerative damage of sepsis by contributing to blood-brain barrier integrity, and by decreasing inflammation, thus the neuroprotective effects of MEL might provide an experimental basis for clinical applications.

Pure Foamy Gland Carcinoma of Prostate - A Series of Rare Cases

Foamy gland carcinoma (FGC) is a distinct histological variant of prostatic acinar adenocarcinomas. It was first described by Epstein and Nelson in 1996. It is characterized by abundant xanthomatous cytoplasm, pyknotic nuclei, and intermediate Gleason grade. However, FGC with a high Gleason grade exists. FGC is found admixed with conventional acinar adenocarcinoma in 17 to 22% of needle biopsies and 13 to 22% of radical prostatectomy specimens and only rarely found in pure form. We report six cases of pure foamy gland carcinoma of prostate. The mean age in our study was 62.83 years and 5 out of the 6 cases presented with an elevated serum PSA level. Histopathological examination of our cases showed tumor cells with abundant foamy cytoplasm and low nucleo-cytoplasmic ratio. This deceptively benign-looking morphology can mimic nonneoplastic prostatic glands, Cowper’s gland, mucinous metaplasia, and xanthomatous prostatitis and hence often pose diagnostic challenges, especially in core needle biopsies. PNI was detected in two of our cases. PSA and AMACR staining was positive in all our cases (100%). p63 Staining was negative in all four cases where it was performed. Three, two, and one of our cases had a Gleason score of 7, 8, and 6 respectively. The prognosis depends on the Gleason score and the presence or absence of PNI or extraprostatic extension. Three of the cases presented with bony metastasis. We report this case series in view of the rarity and also to raise awareness of this entity which is often missed on small biopsies. Keywords: Foamy gland carcinoma, Gleason score, Prostate

Histopatological Changes in Plasenta Previa, Plasenta Acreata and Normotensive Plasentas in the 3rd Trimestry of Pregnancy

Introduction: One of the consequences of improper placentation is placenta previa, a condition in which the placenta is located on or near the internal cervical os. This condition is the major cause of bleeding in the last trimester of pregnancy. It is one of the causes of both maternal and perinatal morbidity and mortality. Placenta accreta is a disorder caused by abnormal invasion of the placental villi into the myometrium. In this study, we aimed to compare the histopathologic changes in placenta previa, placenta acreata and normotensive placentas during the third trimester of pregnancy.&#x0D; Materials and methods: In our study, placentas of a total of 60 pregnant women including 20 placenta previa, 20 placenta acreata and 20 normotensive pregnant women were used and the placentas were compared histopathologically.&#x0D; Results: In the control group placentas, the appearance of endothelial cells was normal, with a slight distribution of erythrocytes in the intervillous areas. Fibrinoid structures were observed to be smooth. Dysfunctional development of endothelial cells was observed in the sections of the placenta acreata group. Congestion and edema were observed in the vessels and degeneration was detected in the cells in the syncytial region. In placenta previa sections, muscle cells showed prominent pyknotic nucleus structures. Dilatations and fibronoid structures were seen in the vessels. Dense erythrocyte accumulation was detected in the intervillous areas.&#x0D; Conclusion: In our study, we concluded that placenta previa and placenta accreta cause very serious degenerations on the placentas.&#x0D; Keywords: Placenta, Placenta Previa, Plasenta Acreata, histopatology

Red Vetchling (Lathyrus cicera L.), a Promising Crop for the Sustainable Replacement of Soybean Meal and Reducing the Carbon Footprint of European Aquafeeds.

In fish diets, soybean meal (SBM) is still positioned as the most widely used alternative to replace fishmeal. Red vetchling (Lathyrus cicera), a crop locally produced in Europe, is here evaluated as a substitute for SBM. Rainbow trout (Oncorhynchus mykiss) juveniles (10.34 ± 0.04 g) were fed for 90 days. Six experimental diets replacing the SBM content at 0, 8, 16, 33, 66, and 100% (Named Control, T8, T16, T33, T66, and T100) were tested. Growth performance and fish fillet amino acid composition were only significantly reduced in fish fed the T100 diet. Histopathological analysis showed that no major alterations were observed in the intestine, while T100 fish had a higher density of pyknotic nuclei in the hepatocytes than the Control, but similar hepatocyte surface coverage. Finally, postprandial levels of glucose and triglycerides in blood plasma decreased when red vetchling content was increased, but was only not fully restored after 24 h in the case of glucose in T66 and T100 fish. According to these results, red vetchling meal can replace up to 66% of the SBM without a negative effect on fish growth or physiology, representing a good alternative raw material for reducing European aquaculture's dependency on SBM imports and the carbon footprint of aquafeeds.

Management of acute Aspergillosis in newly hatched chicks: A case report.

High and early mortalities of chicks often result in colossal economic losses. Aspergillosis, a fungal infection in chicks often occurs in the first 2 weeks of life and may be misdiagnosed as a common respiratory problem like Mycoplasmosis. Some Veterinarians are of the opinion that there is no effective way of treating Aspergillosis. This clinical case report describes the management of acute aspergillosis in chicks. Necropsies were done thrice. Grossly, congested livers, hemorrhagic nephritis, and congested lungs with whitish nodules were observed. Histologically, there were numerous multinuclear giant cells, macrophages and heterophils in the liver. The lung showed fungal hyphae and inflammatory cells. In the kidney, there was severe tubular epithelial necrosis indicated by the pyknotic nuclei, mononuclear infiltrates and haemorrhages. Considering the mortality rate, necropsy findings, microbial isolation and histopathologic observations, systemic Aspergillosis was diagnosed. The secondary bacterial infection was caused by Escherichia coli which was resistant to 8 antibiotics and susceptible only to Penstrep® (Penicillin +streptomycin). Initial resistance to copper sulphate necessitated a change to Nystatin which was used for 12 days via drinking water. Cumulative mortality was 757 (34.37%) in a flock of 2,202 chicks. Better control of systemic fungal infections may be enhanced by early application of anti-fungal susceptibility test.

Evaluation of Imidacloprid Induced Changes in Thyroid Gland and its Amelioration with Withania somnifera in Wistar Rats

The study was conducted on a total of 48 female Wistar rats divided into four groups, each containing 12 rats. Group 1 was control, group 2 was imidacloprid control, group 3 was Withania somnifera control and group 4 was administered with both imidacloprid and Withania somnifera. The rats of group 3 and 4 were subjected to oral treatment of Withania somnifera (1 gm/kg feed) for a period of 30 days to measure the protective effect against thyroid toxicity induced by imidacloprid (30 mg/kg body weight/day for 30 days). Hormonal assays showed a significant (p&lt;0.05) rise in thyroid stimulating hormone and fall in triidothyronine and thyroxine in imidacloprid administered rats when compared to control. No gross lesions were noticed in thyroid gland. Group 2 thyroid gland sections revealed congestion, degenerated thyroid follicles with loss of colloid substance, increase in inter-follicular space, atropic follicles, fibrosis, pyknotic nuclei, detachment of follicular epithelial cells, increase in number of micro-follicles and proliferation of follicular epithelium towards lumen. Electron microscopy of thyroid gland from group 2 rats revealed significant pathological changes. The degree of lesions was minimal in group 4 rats when compared to group 2 rats. These results indicate that Withania somnifera is beneficial in ameliorating the imidacloprid induced thyroid toxicity in rats.

Influence of Chemotherapy on the Relationship between MicroRNA Levels in the Lymph with Thymus Structure in Experimental Breast Cancer.

The relationship between the expression levels of microRNAs (miR-21, miR-221, miR-222, and miR-429) and morphometric parameters of the thymus was studied in female Wistar rats with breast cancer receiving and not receiving chemotherapy. In breast cancer, the following positive relationships were revealed: miR-221 in the subcapsular zone of the cortical substance with medium lymphocytes, miR-221 in the central part of the cortical substance with immunoblasts and macrophages, miR-429 in the subcapsular zone of the cortical substance with mitotically dividing cells, miR-429 in the central part of the medullary substance with macrophages, and miR-21 with medium lymphocytes of the thymus. In the subcapsular zone of the cortical substance, proliferative activity and the number of cells with pyknotic nuclei were increased. After chemotherapy, the relationship of microRNAs in the lymph with transformations in the thymus can indicate destructive processes in the breast tumor in comparison with breast cancer without treatment and indicate strengthening of the antitumor immunity, a decrease in the number of dying cells, and lymphoid depletion of the morphofunctional zones of the thymic parenchyma. Positive relationships of miR-21 with medium and small lymphocytes, miR-221 and miR-429 with epithelial cells, miR-222 with macrophages in the central part of the cortex, and miR-222 with macrophages in the central part of the medulla were found.

Neurobehavioral damage and Th17 cell infiltration in mice exposed to nano carbon black

The effects of nano-carbon black on neural behavior and Th17 cell infiltration in mice were investigated by establishing a mice model of subacute dynamic inhalation of carbon black aerosol. 36 SPF grade male C57BL/6 mice were randomly divided into a control group(clean air), a low carbon black group(15 mg/m~3), and a high carbon black group(30 mg/m~3). Nano-carbon black particles were blown into the dynamic exposure cabinet by aerosol generator for 28 days. Morris water maze test and open field test were used to detect the neural behavior of mice. The pathological changes of prefrontal cortex in mice were observed by HE staining. The proportion of Th17/CD4~+ cells in peripheral blood and brain tissue of mice was detected by flow cytometry. Western blotting was used to detect the protein expression of interleukin(IL)-17 and IL-23 in the prefrontal cortex of mice. The result of open field test showed that compared with the control group, the central area residence time and standing times of mice in the low and high carbon black groups decreased significantly(P&lt;0.05), and the defecation times of mice in the high carbon black group increased significantly(P&lt;0.05). The central area residence time of mice in the high carbon black group was significantly lower than that in the low carbon black group(P&lt;0.05). The Morris water maze result showed that the escape latency of the high carbon black group mice on the 3rd day was significantly higher than that of the control group(P&lt;0.05). Meanwhile, the escape latency of the carbon black group mice on the 4th day was significantly higher than that of the control group(P&lt;0.05). The positioning navigation test showed that the number of mice crossing the platform in the high carbon black group was significantly higher than that in the control group(P&lt;0.05). The HE staining result showed that the neural cells in the prefrontal cortex of the control group mice were round, the cytoplasm was plump and evenly distributed, and the nucleus was clearly visible in an oval shape. The low carbon black group showed that the neural cells were deep staining of nerve cells, blurred structure, and nuclear pyknosis. The high carbon black group further intensified. The flow cytometry result showed that compared with the control group, the percentage of Th17/CD4~+T cells in the peripheral blood of the carbon black group mice was significantly increased, and the high carbon black group mice were significantly higher than the low carbon black group(P&lt;0.05). Meanwhile, the percentage of Th17/CD4~+T cells in the brain tissue of carbon black treated mice significantly increased(P&lt;0.05). The high carbon black group was significantly higher than the low carbon black group(P&lt;0.05). Western blotting result showed that compared with the control group, the expression of IL-17 and IL-23 proteins in the prefrontal cortex of the carbon black group mice brain tissue was significantly increased(P&lt;0.05). Compared with the low carbon black group, the expression of IL-17 and IL-23 proteins in the prefrontal cortex of the high carbon black group mice brain tissue was significantly increased(P&lt;0.05). The difference was statistically significant. Nano-carbon black exposure can lead to an increase in Th17 cells in peripheral blood and brain tissue of mice, which in turn promotes damage to the prefrontal cortex of mice, and ultimately causes neurobehavioral changes in mice.

Oleuropein attenuates placental growth factor expression by regulating oxidative stress and apoptosis in acrylamide hepatotoxicity

The liver is susceptible to toxic effects, as it is the main site of acrylamide biotransformation and detoxification. Researchers have claimed that placental growth factor (PlGF) and its pathway are potentially involved in numerous diseases, including liver fibrosis and angiogenesis. Oleuropein is a natural phenolic compound with potent antioxidant effects. The purpose of this study was to examine the role of PlGF and the potential protection provided by oleuropein in acrylamide hepatotoxicity. Wistar albino rats were assigned into control, acrylamide (ACR) (5 mg/kg), oleuropein (OLE) (4.2 mg/kg), and ACR+OLE groups. Acrylamide and oleuropein were administered for 21 days. The control group received only physiological saline. Liver tissues were evaluated histologically and immunohistochemically. Histological examinations revealed significant enlargement of the sinusoidal vessels and abundant hepatocytes with pyknotic nuclei in the ACR group. Acrylamide toxicity resulted in elevated PlGF, accumulation of 8-hydroxydeoxyguanosine (8-OHdG), and increased Caspase-3 immunoreactivity in the liver. Oleuropein treatment reduced the increased expression of PlGF, 8-OHdG, and Caspase-3 against these deleterious effects observed in the ACR group. A positive correlation was observed between PlGF levels as well as oxidative stress and apoptosis markers in acrylamide toxicity. Oleuropein probably counteracted this mechanism by exhibiting antioxidant activity.

Toxicological and morphological aspects of nano-TiO2 and nano-TiO2-Ag acute action on the liver of mice

Aim. To study the toxic effect of TiO2 and TiO2-Ag nanopowders on the morphology and elemental composition of the laboratory mice liver. Materials and methods. The study used a model of acute intoxication on laboratory animals. Mice were injected intraperitoneally with TiO2 and TiO2-Ag nanopowders at 4000 mg/kg, 7000 mg/kg, or 10000 mg/kg doses. During two weeks, the animals were observed, lethality was assessed, the accumulation of nanopowder in the organ and the morphology of liver tissues were investigated. The content of titanium and silver in liver samples was determined by optical emission spectroscopy with inductively coupled plasma. Liver tissue micropreparations were examined using an Olympus BX51 light microscope. Also, the micropreparations of the liver were examined by scanning electron microscopy (SEM) using the Tescan Mira 3 device, and the elemental composition was determined using an energy dispersive spectrometer Oxford instrument, X-max 80 mm2. Results. The dependence of the mice lethality on the nanopowders dose was revealed; mortality was higher when exposed to nano-TiO2-Ag compared to nano-TiO2. Average lethal doses were calculated using probit analysis. For nano-TiO2, the LD50 is 4783.30 mg/kg; for nano-TiO2-Ag – 724.44 mg/kg. The accumulation of titanium, titanium, and silver in the liver after exposure to nano-TiO2 and nano-TiO2-Ag was established. In general, there was a tendency to increase the content of titanium in the skin tissue with an increase in the administered dose of nanopowders. Morphological changes in the liver were studied by histological methods. The most characteristic morphological signs of the toxic effect of nano-TiO2 on tissue were dystrophic changes at the level of 67.7 % (cytoplasmic vacuolization in hepatocytes), and when exposed to nano-TiO2-Ag – initial necrotic changes at the level of 70 % (hepatocytes with nuclear pyknosis). It is worth noting that the toxic effect of nano-TiO2 and nano-TiO2-Ag is much less often manifested by focal necrosis and inflammatory reactions (focal infiltration), in some cases, there were adaptive changes that provoked an increase in the number of binuclear hepatocytes. In case of detection agglomerates of a foreign object (crystalline inclusions) were obtained, which were examined spectrally and showed a high content of titanium (Ti). SEM morphometry showed that the size of nanoparticles and their agglomerates ranged from 80 nm to 20 μm. Conclusions. The lethality of mice was higher when the composition of nano-TiO2-Ag was introduced compared to nano-TiO2. Based on the calculated average lethal doses, both nanopowders were assigned to the 3rd class (moderately dangerous) of the danger of chemical substances according to the classification of GOST 12.1.007-76. It was established that with an increase in the injected dose in the tissue of the products of laboratory mice, the accumulation of titanium (under the action of nano-TiO2) and titanium and silver (under the action of nano-TiO2-Ag) increases. Characteristic microscopic signs of the toxic effect of TiO2 and TiO2-Ag nanopowders after intraperitoneal injection in laboratory bags are dystrophic changes in hepatocytes, necrosis of parenchymal disease, while inflammatory reactions occur less often. SEM and the method of elemental mapping of titanium confirmed the presence of TiO2 nanoparticles and their agglomerates in skin tissue when TiO2 nanopowder was administered.

Effect of melatonin on the liver histophysiology of adolescent rats exposed to alcohol

The present study evaluated whether melatonin administered during adolescence can prevent the deleterious effects produced by alcohol on the liver. Thirty albino female rats (Rattus norvegicus albinus), 40 days old, virgins, weighing approximately 150±10g, from the Wistar lineage and were divided into the following groups: I – Adolescent rats that did not receive alcohol and euthanized at 60 days of life; II – Adolescent rats subjected to chronic alcohol consumption and euthanized at 60 days of life; III – Adolescent rats subjected to chronic alcohol consumption and simultaneously treated with melatonin, and euthanized at 60 days of life. The collected organs underwent histological processing and to obtain the results, morphometric, histopathological and histochemical analyzes were performed. Alcohol was administered by gavage. intragastric injection at a dosage of 3 g/Kg of ethyl alcohol in the rats of groups II and III for 20 days. Melatonin was administered in daily injections of 0.8 mg/Kg, always at the beginning of the night, intraperitoneally for 20 days. When analyzing the weight of the animals, no significant difference was observed between the groups. The animals in group II presented alterations in the livers such as congestion of the centrilobular vein, hepatocellular ballooning, microgoticular steatosis, leukocyte infiltrate, several pyknotic nuclei in the livers, increase in lobular parenchyma and reduction in non-lobular parenchyma, greater deposition of collagen and reduction of glycogen. Melatonin treatment prevented all these changes. With this, we can conclude that melatonin has great therapeutic potential in the prevention of liver damage in adolescent rats subjected to moderate alcohol consumption, in addition to positive effects on the deposition of collagen and glycogen in the liver.

Effects of aerobic exercise on depression-like behavior and TLR4/NLRP3 pathway in hippocampus CA1 region of CUMS-depressed mice

Background and purposeThe paper observes regulation of the expression levels of NLRP3 and TLR4 in hippocampal CA1 neurons in CUMS mice by aerobic exercise with constructing CUMS depression mouse model, in order to explore the neuroprotective mechanism of aerobic exercise on the hippocampus of depressed mice. Study design and method24 healthy male 8-week-old C57BL/6 mice were randomly divided into CG, MG and ME. Thirteen stress-stimulating factors were randomly formulated into a CUMS stress-stimulating program. The mice were underwent 28 days of CUMS depression model, referenced clinical means for experimental research. The study was approved by the Ethics Committee of Yichun University (YCUEC IRB number LSK NO.2022.18). After model preparation, ME mice were subjected to moderate-intensity treadmill exercise training for 8 weeks. TST, FST and SPT were used to detect the depression-like behaviors of the mice in each group. Nissl staining was used to compare the cell morphology in the CA1 region of the mouse hippocampus. Immunohistochemical staining and western blot were used to detect the changes in the expression levels of NLRP3, TLR4 and other proteins in the CA1 region of the mouse hippocampus. ResultsThe results of neurobehavioral assessment showed that, the immobility time of TST and FST were significantly increased, and SPT index was significantly decreased of MG mice. Compared with MG, ME mice significantly improved depression-like behaviors such as TST, FST and SPT index. Nissl staining showed that the morphology of neurons in CA1 region of hippocampus of MG mice were mostly vacuolar-like, with severe nuclear pyknosis. Abnormal morphological changes such as vacuolar-like and pyknotic pyknosis of neurons in the hippocampal CA1 region of ME mice were significantly reduced. Protein expression test showed that the number of NLRP3, TLR4, IL-1β and IL-10 positive neurons in hippocampal CA1 region of MG mice increased significantly compared with CG, and the proportion of positive cells increased significantly, while NLRP3 and TLR4 positive neurons in the hippocampal CA1 region of ME mice were significantly reduced, the proportion of TLR4 positive cells was significantly reduced. ConclusionSystematic moderate-intensity exercise can effectively improve the depression-like behavior of CUMS depressed mice through the expression of TLR4/NLRP3 inflammatory signaling pathway, and provide an effective experimental basis for the clinical rehabilitation treatment of depression.