Nuclear Degeneration Research Articles

The Effects of Memantine on Cisplatin-induced Ototoxicity

Introduction: We aimed to investigate electrophysiologically and histopathologically, the protective effects of intratympanic memantine, an N-methyl-D-aspartate receptor antagonist, on ototoxicity caused by cisplatin, an anti-neoplastic agent used in many types of cancer. Methods: Thirty-seven guinea pigs with a normal auditory function were randomly allocated to group 1 (Cisplatin; n=8), group 2 (Memantine; n=8), group 3 (Cisplatin+Memantine; n=8), group 4 (Cisplatin+Physiological Serum [PS]; n=8), and group 5 (Control; n=5). Auditory assessments were conducted using distortion product otoacoustic emissions (DPOAE) within a frequency range of 1-32 kHz, and auditory brainstem responses (ABR) within 8-32 kHz. A single dose of cisplatin (12 mg/kg) was administered intraperitoneally, followed by intratympanic administration of 0.2 mL of either memantine or PS to both ears at least half an hour before cisplatin administration. Subsequent auditory evaluations were conducted 72 h after cisplatin administration. Histopathological analyses were performed using light microscopy of the right ear and scanning electron microscopy (SEM) of the left ear. Results: Auditory evaluations conducted before and after treatment revealed significant findings. Specifically, within groups 3 and 4, ABR thresholds were elevated at all frequencies (p=0.00), whereas the DPOAE signal-to-noise ratios were reduced at frequencies of 8, 12, 16, and 24 kHz (p=0.001, p=0.01, p=0.01, and p=0.00, respectively). Histopathologically, both light microscopy and SEM revealed that the cisplatin+memantine group exhibited fewer hair cells and nuclear degeneration in the spiral ganglion than the cisplatin and cisplatin+PS groups. Additionally, the stria vascularis thickness was greater in the cisplatin+memantine group than in cisplatin and cisplatin+PS groups. Conclusion: Despite the negative electrophysiological findings, the histopathological outcomes suggest that intratympanic memantine may have a potential protective effect against cisplatin-induced ototoxicity. However, further investigations are warranted to corroborate these findings and elucidate the underlying mechanisms of action of memantine.

Mitigation of methylglyoxal-induced hepatotoxicity by Boerhavia diffusa L. aerial extract: Insights from cellular and animal models

BackgroundBoerhavia diffusa (Punarnava), is a perennial herb with a long-standing reputation for its antioxidative and anti-inflammatory properties, dating back to ancient times. Methylglyoxal is an advanced glycation end-product, known to be toxic in liver cell line as well as in mice model. Our objective is to illustrate the protective action of punarnava aerial extracts in methylglyoxal-induced hepatotoxicity in cell line and mice model. MethodsPunarnava aerial parts were collected and different solvent extracts were prepared in methanol, dichloromethane and hexane by maceration followed by their LCMS/MS characterization, determination of total phenolic, total flavonoid contents and antioxidant activity by DPPH reagent. Cell viability of the extracts and methylglyoxal was assessed using different cell lines. In vitro protective effect of punarnava methanolic extract (PME) against methylglyoxal was evaluated by cell migration assay, NO and ROS production assays and Oil Red O staining in HepG2 cell line. BALB/c mice were pretreated with Punarnava methanolic extract (200 mg/kg and 400 mg/kg) for seven days followed by 290 mg/kg methylglyoxal administration for 6 hrs to induce hepatotoxicity. Serum glucose, AST, ALT, ALP and GSH level were checked and liver histopathological damages were identified. ResultsAmong the three Punarnava extracts, PME possessed maximum antioxidant, total phenolic and flavonoid content as well as least cytotoxic to liver cell line. Methylglyoxal showed maximum toxicity in HepG2 cells with IC50 (50 % inhibitory concentration) 3 µM. PME confers protection against methylglyoxal-induced cytotoxicity by decreasing ROS, promoting cell migration and preventing loss of cell viability. No significant change was observed in NO production and Oil Red O staining. PME-treated mice showed decrease in liver ALP levels and glucose with intact cellular morphology compared to hepatocyte steatosis and nuclear degeneration in methylglyoxal-treated group. DiscussionsIndigenous herb Punarnava is effective in protecting liver cells from damage induced by the glycolytic byproduct, methylglyoxal.

Histological investigation of the liver of freshwater fish Cyprinus carpio after intoxication with Ibuprofen

Water contamination has a detrimental impact on streams and rivers, leading to a reduction in the diversity of terrestrial, aquatic, and aerial species. Furthermore, it disrupts the intricate equilibrium of existence. Pharmaceuticals are artificial compounds that belong to several chemical families and exhibit a diverse array of environmental biochemical responses, rendering them the most recent group of pollutants in all aquatic environments. The present study investigated the impact of Ibuprofen on freshwater fish Cyprinus carpio by determining the LC50 value of Ibuprofen during exposure to various concentrations for 24, 48, 72, and 96 hours in sets of aquariums at a concentration of 0.23ml/L. To investigate the impact of Ibuprofen on fish C. carpio, the study evaluates the effects of a sublethal concentration of 1/10th (0.023ml/L) of Ibuprofen LC50 on fish liver histology over a period of 7, 14, 21, and 28 days in both control and treatment aquarium cultures. Following exposure to a sublethal dose of Ibuprofen, significant changes in the behavior of fish and disruption of normal physiology were observed. These changes were clearly displayed through nuclear degeneration, cellular edema, cytoplasmic degeneration, altered hepatocytes, formation of vacuole, increased sinusoidal space, altered central vein, and degeneration of sinusoid. These results indicated that the release of pharmaceuticals had a significant negative impact on fish health and highlighted deterioration in water quality and the ecology of water resources .

Age changes in the gastric mucosa of male albino rat: histological, immunohistochemical, histomorphometric and biochemical study.

Age related changes in the stomach are associated with alterations in the structure and secretory function of the gastric glands. The present study aimed to investigate histological, histomorphometric and biochemical changes in the gastric mucosa of rats with age. Eighty adult male albino rats were randomly divided into four age groups, 20 rats in each (prepubertal, adolescent, adult, and senile). The gastric specimens were subjected to light microscopic examination using haematoxylin and eosin, PAS and Masson's trichrome stains. Immunohistochemical staining for caspase-3 and inducible nitric oxide synthase (iNOS) was carried out. Measurement of superoxide dismutase (SOD), glutathione peroxidase (GPx) and malondialdehyde (MDA) activity in gastric tissue homogenates was performed using ELISA. Quantitative analysis of vascular endothelial growth factor (VEGF) gene expression was done by real-time polymerase chain reaction (PCR). Light microscopic examination of gastric mucosa of senile rats revealed distortion of gastric glands and erosions. Surface mucous cells, mucous neck cells, parietal and chief cells exhibited cytoplasmic destruction, nuclear degeneration, apoptosis and oxidative damage. There was a significant decrease in the mean gastric mucosal thickness, increase in collagen content and decrease in mucous content with the advance of age. These morphological changes were associated with a significant decrease in SOD and GPx activity and increase in MDA activity, in addition to decreased VEGF gene expression. Gastric mucosa of aged rats showed histological and immunohistochemical alterations. These changes were associated with oxidative stress, decreased antioxidant capacity and decreased angiogenesis.

Thalamic nuclei segmentation from T1-weighted MRI: Unifying and benchmarking state-of-the-art methods

Abstract The thalamus and its constituent nuclei are critical for a broad range of cognitive, linguistic, and sensorimotor processes, and are implicated in many neurological and neurodegenerative conditions. However, the functional involvement and specificity of thalamic nuclei in human neuroimaging work is underappreciated and not well studied due, in part, to technical challenges of accurately identifying and segmenting nuclei. This challenge is further exacerbated by a lack of common nomenclature for comparing segmentation methods. Here, we use data from healthy young (Human Connectome Project, n = 100) and older healthy adults, plus those with mild cognitive impairment and Alzheimer’s disease (Alzheimer’s Disease Neuroimaging Initiative, n = 540), to benchmark four state-of-the-art thalamic segmentation methods for T1 MRI (FreeSurfer, histogram-based polynomial synthesis [HIPS]-THOMAS, synthesized contrast segmentation [SCS]-convolutional neural network [CNN], and T1-THOMAS) under a single segmentation framework. Segmentations were compared using overlap and dissimilarity metrics to the Morel stereotaxic atlas, a widely accepted thalamic atlas. We also quantified each method’s estimation of thalamic nuclear degeneration across Alzheimer’s disease progression, and how accurately early and late mild cognitive impairment, and Alzheimer’s disease could be distinguished from healthy controls. We show that the HIPS-THOMAS approach produced the most effective segmentations of individual thalamic nuclei relative to the Morel atlas, and was also most accurate in discriminating healthy controls from those with mild cognitive impairment and Alzheimer’s disease using individual nucleus volumes. This latter result was different when using whole thalamus volumes, where the SCS-CNN approach was the most accurate in classifying healthy controls. This work is the first to systematically compare the efficacy of anatomical thalamic segmentation approaches under a unified nomenclature. We also provide recommendations of which segmentation method to use for studying the functional relevance of specific thalamic nuclei, based on their overlap and dissimilarity with the Morel atlas.

Tannic acid coated nanosuspension for oral delivery of chrysin intended for anti-schizophrenic effect in mice

Chrysin is a flavonoid drug with numerous therapeutic activities. It suffers from low intestinal absorption owing to its hydrophobicity. Therefore, the aim of this study is to exploit the efficient technique of nanosuspension (NSP) to formulate chrysin-NSP coated with tannic acid (TA) to improve the solubility and anti-schizophrenic activity of chrysin. A 23 full factorial design was constructed where the independent factors were type of polymer, surfactant concentration (0.5 or 1 %) and the aqueous phase volume (5 or 15 mL), while the dependent responses were the particle size (PS) of the obtained formulation as well as the % chrysin dissolved after 2 h (Q2h). The optimum formulation (NSP-4) composed of 1 % PEG 400 and 1 % Cremophor RH40 in 15 mL aqueous phase. It achieved a PS and Q2h values of 108.00 nm and 38.77 %, respectively. NSP-4 was then coated with TA (TA-coated NSP-4) for further enhancement of chrysin solubility. TA-coated NSP-4 revealed PS and zeta potential values of 150 ± 14 nm and –32.54 ± 2.45 mV, respectively. After 6 h, chrysin dissolved % were 53.97 and 80.22 for uncoated NSP-4 and TA-coated NSP-4, respectively, compared with only 9.47 for free chrysin. The developed formulations and free chrysin were assessed regarding their effect on schizophrenia induced in mice by cuprizone (CPZ). Treatment with the developed formulations and free chrysin ameliorated demyelination and behavioral deficit induced by CPZ via elevating MBP and PI3K/PKC activities as well as reducing GFAP expression levels. The developed formulations and free chrysin inhibited Galactin-3 and TGF-β expressions and stimulated GST antioxidant enzyme. Furthermore, they maintained the balances in glutamatergic and dopaminergic neurotransmission via modulation on neuregulin-1 and alleviated nuclear pyknosis and degeneration in the neurons. The order of activity was: TA-coated NSP-4 > NSP-4 > free chrysin.

Hypoxia alters the upper thermal limits and blood physiology in zebrafish, Danio rerio

Hypoxic aquatic environments occur more frequently as a result of climate change, thereby exerting challenges on the physiological and metabolic functions of aquatic animals. In this study, a model fish, zebrafish (Danio rerio) was used to observe the climate-induced hypoxic effect on the upper thermal limit (critical thermal maximum; CTmax), hemoglobin, and blood glucose levels, and abnormalities of erythrocytes at cellular and nuclear level. The value of CTmax decreased significantly under hypoxia (39.10 ± 0.96 °C) compared to normoxia (43.70 ± 0.91 °C). At CTmax, hemoglobin levels were much lower (9.33 ± 0.60 g/dL) and blood glucose levels were significantly higher (194.20 ± 11.33 mg/L) under hypoxia than they were under normoxia and at the beginning of the experiment. Increased frequencies of abnormalities in the erythrocytes at both cellular (fusion, twin, elongated, spindle and tear drop shaped) and nuclear (micronucleus, karyopyknosis, binuclei, nuclear degeneration and notched nuclei) levels were also found under hypoxia compared to normoxia. These results suggest that hypoxic conditions significantly alter the temperature tolerance and subsequent physiology in zebrafish. Our findings will aid in the development of effective management techniques for aquatic environments with minimum oxygen availability.

Müller cells are activated in response to retinal outer nuclear layer degeneration in rats subjected to simulated weightlessness conditions.

JOURNAL/nrgr/04.03/01300535-202507000-00032/figure1/v/2024-09-09T124005Z/r/image-tiff A microgravity environment has been shown to cause ocular damage and affect visual acuity, but the underlying mechanisms remain unclear. Therefore, we established an animal model of weightlessness via tail suspension to examine the pathological changes and molecular mechanisms of retinal damage under microgravity. After 4 weeks of tail suspension, there were no notable alterations in retinal function and morphology, while after 8 weeks of tail suspension, significant reductions in retinal function were observed, and the outer nuclear layer was thinner, with abundant apoptotic cells. To investigate the mechanism underlying the degenerative changes that occurred in the outer nuclear layer of the retina, proteomics was used to analyze differentially expressed proteins in rat retinas after 8 weeks of tail suspension. The results showed that the expression levels of fibroblast growth factor 2 (also known as basic fibroblast growth factor) and glial fibrillary acidic protein, which are closely related to Müller cell activation, were significantly upregulated. In addition, Müller cell regeneration and Müller cell gliosis were observed after 4 and 8 weeks, respectively, of simulated weightlessness. These findings indicate that Müller cells play an important regulatory role in retinal outer nuclear layer degeneration during weightlessness.

Microtubule response to salt stress

This study has aimed to investigate the relationship between salt stress, programmed cell death (PCD) and microtubule distribution in terms of duration and stress dose. PCD is an important mechanism that benefits living organisms throughout their lives. On the other hand, PCD is an indirect effect that reduces efficiency when it occurs under stress. In this research The maize (Zea mays) roots were exposed to salt stress with 0, 50, 100, 300 and 500 mM NaCl. The prepared paraffin sections of these five groups were subjected to DAPI (4-6-diamidino-2-phenylindole) and TUNEL analysis to study the morphological changes caused by stress-induced nuclear degeneration. PCD was determined. Microtubule labeling analysis was performed on the tissues to determine whether there were stress-induced microtubule changes in these cells and disturbances were found; they exhibited aggregation, regional thickening, and random distribution around the nucleus and vacuole and under the cell wall. When all groups were evaluated, cells exposed to a salt concentration of 50 mM (even after 24 hours) were significantly less damaged than cells at other concentrations (100, 300, and 500 mM) at each time point. The rate of progression and spread to the whole tissue was significantly higher at 300 and 500 mM salt concentrations compared to the other groups. To reduce economic losses in salty soils, it is of great importance to fully investigate stress. The data that will emerge from our research, which is the subject of a small number of studies, will help to understand the mechanism of stress, microtubule and PCD.

Prospective hepatotoxic effect of UV-328 and its affirmable rescue by Dimethoxy curcumin in Zebrafish

The unprecedented usage of BUV-328 (Benzotriazole Ultraviolet Stabilizer) in many biological and environmental matrices is of acute environmental importance because of its toxicity even at low concentrations. To better understand the protective function of DiMC on the liver tissues of zebrafish exposed to sublethal concentration of BUV-328 was assessed in the present investigation. Adult zebrafish were exposed to BUV-328 at sublethal concentrations of 55µg/l. The responses were assessed in the liver tissues at 28 days and another group was supplemented with DiMC to investigate its ameliorative potential against BUV-328 induced hepatotoxicity. Biochemical markers of oxidative stress, histopathological changes, and antioxidant enzymes were measured in the exposed groups. The outcomes of our present study revealed that BUV-328 exposure upregulated the oxidative stress markers and diminished the activities of the antioxidant enzymes, altered the biochemical constituents in liver. Histopathological abrasions such as hypertrophy, cellular and nuclear enlargement, cytoplasmic and nuclear degeneration, necrosis with pyknotic nuclei, lipid and cytoplasmic vacuolization and nuclear displacement to the periphery were found to be increased in BUV-328 exposure group. The oxidative, biochemical and histological alterations induced by BUV-328 were almost recuperated in DiMC supplemented group which signifies its protective influence against BUV-328 incited hepatotoxicity.

Evaluation of the biological efficiency of Terminalia chebula fruit extract against neurochemical changes induced in brain of diabetic rats: an epigenetic study

Diabetes mellitus (DM) is a chronic and progressive metabolic disorder that can stimulate neuroinflammation and increase oxidative stress in the brain. Therefore, the present study was aimed to assess the efficacy of ethanolic Terminalia chebula extract against the neurochemical and histopathological changes induced in the brains of diabetic rats. The study clarified the reduction in oxidative stress induced in the brains of diabetic rats by the significant (P ≤ 0.05) increase in levels of the antioxidants with decreasing the peroxidation products via ethanolic T. chebula extract at both doses (400 and 600 mg/kg). Moreover, T. chebula extract improved the brain integrity by lowering levels of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), β-amyloid (Aβ) content, monocyte chemoattractant protein-1 (MCP-1) and acetylcholine esterase (ACHE) significantly (P ≤ 0.05) in a dose dependent manner compared to brain of diabetic rats. Severe nuclear pyknosis and degeneration were noticed in neurons of the cerebral cortex, hippocampus and striatum in brains of diabetic rats. The severity of these alterations decreased with T. chebula extract at a dose of 600 mg/kg compared to the other treated groups. The different electrophoretic protein and isoenzyme assays revealed that the lowest similarity index (SI%) values exist in the brains of diabetic rats compared to the control group. The quantity of the most native proteins and isoenzyme types increased significantly (P ≤ 0.05) in the brains of diabetic rats, and these electrophoretic variations were completely diminished by T. chebula extract. The study concluded that T. chebula extract ameliorated the biochemical, histopathological and electrophoretic abnormalities induced in the brains of diabetic rats when administered at a dose of 600 mg/kg.

Potential Nephrotoxic Effect of UV-328 and Its Possible Salvage by Dimethoxy Curcumin in Zebrafish

The occurrence of Benzotriazole UV Stabilizer-328 (UV-328) in different environmental and natural systems is of fast regular concern these days. In this current paper, we assessed the renotoxicity of UV-328 in zebrafish kidney tissues to know the chore of oxidative devilry in kidney and to recuperate the renotoxicity utilizing Dimethoxy curcumin (DiMC) supplementation. Grown-up zebrafish were exposed 55µg/L of UV-328 and DiMC supplemented through diet at 50mg/kg BW. Close to the completion of 28 days, renal tissues were examined for the responses of oxidative pressure, antioxidant status and histopathological changes. The results demonstrated that antioxidant enzymes such as, Glutathione (GSH) levels and the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione-S-transferase (GST) were all reduced in zebra fish kidneys treated with UV-328. Renal malondialdehyde (MDA) levels was brought prominently up in the UV-328 treated fish. All of the altered variables significantly returned to near-normal levels in the DiMC-supplemented group. Histopathological lesions, viz., hypertrophied glomerulus, cytoplasmic and nuclear degeneration, cytoplasmic vacuolization, degeneration of renal tubules were seen in UV-328 treated kidney of zebrafish which were actually reinforced in the DiMC treated fish. From our outcomes, it has been proposed that even at the low-level convergence of UV-328 exposure is malicious and to provoke oxidative insult, cell reinforcement exhaustion and kidney neurotic devilry in zebrafish and remediation with DiMC has been ended up being the better choice to conquer the harmful oppression prompted by UV-328.

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.

Effect of photoperiod on serum biochemistry, electrolytic balance, acute phase response and histopathology of butter catfish, Ompok bimaculatus (Bloch, 1794).

The present study was executed to evaluate the effect of photoperiod on serum biochemical parameters (glucose, cortisol, ALT, AST and LDH), electrolytic balance (Sodium and potassium), acute phase response (CRP) and histopathology (liver, kidney and skin) of an endangered high valued catfish, Ompok bimaculatus. Catfish (21.00 ± 1.53cm and 30.00 ± 2.31g) from the acclimatized stock were randomly distributed to six 120 × 45 × 60 cm3 FRP tanks (n = 20 fish per tank) and exposed to 1500lx light intensity under different photoperiods [24:0 light: dark (L: D), 15L: 9D, 12L: 12D, 9L: 15D, 0L: 24D and a natural photoperiod (control)], and fed at a daily rate of 2% of bodyweight, twice a day for 60days. Serum glucose, cortisol and enzymes including aspartate transaminase (AST), lactate dehydrogenase (LDH), alanine transaminase (ALT), and acute phase reactant, such as C-reactive protein (CRP) increased significantly (P < 0.05) in continuous light (24L: 0D), continuous dark (0L: 24D) and short day (9L: 15D) photoperiods, whereas in 15L: 9D and 12L:12D photoperiods, those were in decreasing trend. Serum electrolytes, i.e. potassium level was elevated and sodium level was declined in 24L: 0D, 0L: 24D and 9L: 15D photoperiod groups. Moreover, significant histological alterations in the liver, kidney and skin tissue were also evidenced in the experimented catfish. Typical polygonal hepatocytes with normal blood vessels in liver and normal organization of kidney were seen in catfish of 15L: 9D group. Histological analysis of other groups displayed nuclear degeneration, karyorrhexis, karyolysis, melanomacrophages, nuclear hypertrophy, sinusoid dilation and vacuolar degeneration in liver and hyaline droplets accumulation, granular degeneration, fragmentation of glomerulus and focal necrosis of epithelial cells in kidney. Additionally, general structure of the skin was observed in control group as well as in 15L: 9D group. Contrarily, in 24L: 0D group increased number of mucous cells and vacuoles was observed in the skin of butter catfish. In 9L: 15D and 0L: 24D photoperiods, O. bimaculatus exhibited ruptured epithelial cells, enlarged alarm cells, fat cells, necrotic cells and vacuoles in the skin tissue. The present study depicted that 15L: 9D photoperiod can induce better health of catfish, O. bimaculatus, which, in turn, can help farmers to increase the production of this high valued catfish in future.

Cytological studies reveal high variation in ascospore number and shape and conidia produced directly from ascospores in Morchella galilaea.

Spores are important as dispersal and survival propagules in fungi. In this study we investigated the variation in number, shape, size and germination mode of ascospores in Morchella galilaea, the only species of the genus Morchella known to fruit in the autumn. Based on the observation of five samples, we first discovered significant variation in the shape and size of ascospores in Morchella. One to sixteen ascospores were found in the asci. Ascospore size correlated negatively with ascospore number, but positively with ascus size, and ascus size was positively correlated with ascospore number. We noted that ascospores, both from fresh collections and dried specimens, germinated terminally or laterally either by extended germ tubes, or via the production of conidia that were formed directly from ascospores at one, two or multiple sites. The direct formation of conidia from ascospores takes place within asci or after ascospores are discharged. Using laser confocal microscopy, we recorded the number of nuclei in ascospores and in conidia produced from ascospores. In most ascospores of M. galilaea, several nuclei were observed, as is typical of species of Morchella. However, nuclear number varied from zero to around 20 in this species, and larger ascospores harbored more nuclei. One to six nuclei were present in the conidia. Nuclear migration from ascospores to conidia was observed. Conidia forming directly from ascospores has been observed in few species of Pezizomycetes; this is the first report of the phenomenon in Morchella species. Morphological and molecular data show that conidial formation from ascospores is not found in all the specimens of this species and, hence, is not an informative taxonomic character in M. galilaea. Our data suggest that conidia produced from ascospores and successive mitosis within the ascus may contribute to asci with more than eight spores. The absence of mitosis and/or nuclear degeneration, as well as cytokinesis defect, likely results in asci with fewer than eight ascospores. This study provides new insights into the poorly understood life cycle of Morchella species and more broadly improves knowledge of conidia formation and reproductive strategies in Pezizomycetes.

Acute and Sub-chronic Toxicity of Aqueous Extract of Roots of Khaya senegalensis (Desr.) A. Juss. in Mice and Rats Respectively

Aim: Khaya senegalensis is one of the key medicinal plants used discretionarily in traditional medicine as remedies to several health conditions. This study aimed to establish the safety of Khaya senegalensis root aqueous extract in experimental animals with the purpose of optimizing its therapeutic value. &#x0D; Methodology: A total of 74 animals (20 rats and 54 mice) were randomly assigned into two main groups based on toxicity plan; acute and sub-chronic toxicity. Mice were divided into 9 groups (6 per group) for the acute toxicity study while rats were divided into 4 groups (5 per group) for sub-chronic toxicity assessment. &#x0D; Results: The acute concentrations of the extract in mice induced dose-dependent clinical signs severities such as: twitching, increase rate of respiration, sedation, abdominal muscle contractions and increased motor activity. The lethal dose 50 value of the extract was estimated as 320mg/ kg body. The sub-chronic concentrated grades in the rats especially the higher doses elicited significantly increased serum liver enzymes values when compared to the control, while at low dose the values were comparable to that of the control. Also observed were the evidences of renal cellular pathology ranging from mild to severe tubular cell degeneration, tubular cell depletion and congestion of the renal cortex. The liver pathologies such as hepatic portal congestion, cytoplasmic vacuolations and nuclear degeneration were strikingly visible mostly at the higher doses. The lymphocyte and platelet counts were the only haematological parameters that increased significantly more particularly at low dose when compared with the control.&#x0D; Conclusion: This study has shown that Khaya senegalensis seems to be safe only at low doses. However, caution should be taking in its administration for therapeutic purposes especially when long-term usage is desired.

Site-specific genotoxicity of rubiadin: localization and histopathological changes in the kidneys of rats.

Rubiadin (Rub) is a genotoxic component of madder color (MC) that is extracted from the root of Rubia tinctorum L. MC induces renal tumors and preneoplastic lesions that are found in the proximal tubule of the outer stripe of the outer medulla (OSOM), suggesting that the renal carcinogenicity of MC is site specific. To clarify the involvement of Rub in renal carcinogenesis of MC, we examined the distribution of Rub in the kidney of male gpt delta rats that were treated with Rub for 28days. We used desorption electrospray ionization quadrupole time-of-flight mass spectrometry imaging (DESI-Q-TOF-MSI), along with the histopathological analysis, immunohistochemical staining, and reporter gene mutation assays of the kidney. DESI-Q-TOF-MSI revealed that Rub and its metabolites, lucidin and Rub-sulfation, were specifically distributed in the OSOM. Histopathologically, karyomegaly characterized by enlarged nuclear and microvesicular vacuolar degeneration occurred in proximal tubule epithelial cells in the OSOM. The ɤ-H2AX- and p21-positive cells were also found in the OSOM rather than the cortex. Although dose-dependent increases in gpt and Spi- mutant frequencies were observed in both the medulla and cortex, the mutant frequencies in the medulla were significantly higher. The mutation spectra of gpt mutants showed that A:T-T:A transversion was predominant in Rub-induced gene mutations, consistent with those of MC. Overall, the data showed that the distribution of Rub and its metabolites resulted in site-specific histopathological changes, DNA damage, and gene mutations, suggesting that the distribution of genotoxic components and metabolites is responsible for the site-specific renal carcinogenesis of MC.

Sulfoxaflor influences the biochemical and histological changes on honeybees (Apis mellifera L.)

Pesticide application can have an adverse effect on pollinator honey bees, Apis mellifera L., ranging from mortality to sublethal effects. Therefore, it is necessary to understand any potential effects of pesticides. The present study reports the acute toxicity and adverse effects of sulfoxaflor insecticide on the biochemical activity and histological changes on A. mellifera. The results showed that after 48 h post-treatment, the LD25 and LD50 values were 0.078 and 0.162 µg/bee, respectively, of sulfoxaflor on A. mellifera. The detoxification enzyme activity shows an increase of glutathione-S-transferase (GST) enzyme on A. mellifera in response to sulfoxaflor at LD50 value. Conversely, no significant differences were found in mixed-function oxidation (MFO) activity. In addition, after 4 h of sulfoxaflor exposure, the brains of treated bees showed nuclear pyknosis and degeneration in some cells, which evolved to mushroom shaped tissue losses, mainly neurons replaced by vacuoles after 48 h. There was a slight effect on secretory vesicles in the hypopharyngeal gland after 4 h of exposure. After 48 h, the vacuolar cytoplasm and basophilic pyknotic nuclei were lost in the atrophied acini. After exposure to sulfoxaflor, the midgut of A. mellifera workers showed histological changes in epithelial cells. These findings of the present study showed that sulfoxaflor could have an adverse effect on A. mellifera.

Substituting Fish Meal with Tubiechong (Eupolyphaga sinensis) By-Product in the Diets of Largemouth Bass (Micropterus salmoides): Effects on Growth, Meat Quality, and Liver Health.

A feeding trial was conducted to evaluate the effect of replacing 0% (control), 10% (T10), 20% (T20), 30% (T30), and 40% (T40) fish meal with a Tubiechong (Eupolyphaga sinensis) by-product in largemouth bass (Micropterus salmoides). Triplicate groups of 30 fish (5.36 ± 0.01 g) were fed two times daily to apparent satiation for 60 days. The experimental results showed that the Tubiechong by-product could improve the growth performance of largemouth bass by increasing the FBW, WGR, and SGR until the replacement ratio was 40%. The quadratic regression analysis showed that the proportion of the Tubiechong by-product was 20.79% and 20.91%, respectively, when WGR and SGR were the best. Concurrently, the meat quality in the replacement groups was higher, specifically, the lightness and white values were higher, and the water loss rates were lower (P < 0.05) than that in the control group. Moreover, the changes of the activities of CAT and GSH in the liver and T-AOC and GSH in serum could reveal the antioxidant capacity improvement of fish by the Tubiechong by-product. In the study, the replacement groups had lower T-CHO and HDL-C in serum (P < 0.05), indicating that the Tubiechong by-product had an active role in improving blood lipid and regulating lipid metabolism. Simultaneously, the replacement groups had a normal structure with central hepatocytes' nuclei and deviated from the center partly, while most of the hepatocytes were swollen in the control group with nuclear degeneration. The results showed that the Tubiechong by-product had a positive effect on the liver health of fish. Conclusively, the present study indicated that the partial dietary replacement of fish meal using the Tubiechong by-product (for up to 40% replacement level) in the diet of largemouth bass not only caused no adverse effects on fish health but also improved the growth performance, meat quality, antioxidant capacity, and hepatic health and is conducive to supplying nutritious, high-quality, and healthy aquatic products.

High-casein diet restores the redox balance in the liver and pancreatic health of mice when exposed to radiation during call mode from mobile phones

Introduction: The current lives of human beings cannot be imagined without cellular phones and electronic gadgets. Still, the probabilityof being exposed to their harmful radiation is unabated which demands an immediate intervention to shield humankind from beingaffected by using such devices. In our current investigation, we aimed to check the role of a high-casein diet as a protective measureagainst the biological effects of electromagnetic radiation (EMR) emerging from mobile phones on hepatic and pancreatic systemsMethods: Swiss albino mice (n=24) were fed on a standard laboratory diet (ND; n=12) and an isocaloric high-casein diet (HCD; n=12).Six mice from each dietary group were exposed to mobile phone radiation for 3 hours/day within a 3 months span. Histopathologicalalterations were studied in hepatic and pancreatic tissues by using Periodic acid-Schiff (PAS)-hematoxylin and routine H&amp;E stainingmethods. Biochemical evaluation of total serum protein, lipid profile and glucose, total glutathione, oxidized glutathione, and antioxidantenzymatic activities of hepatic tissues were performed. Results: Hyperglycemia was noticeable along with a reduced number and areaof islets of Langerhans in radiation-exposed mice when compared to other groups. This was supported by the observation of depletedglycogen reserves in their liver. Additionally, distorted hepatic morphology with nuclear degeneration was suggestive of apoptoticprogression. The total glutathione pool was reduced on radiation exposure, hint at redox imbalance. HCD was competent in preservingthe normal pancreas and liver functioning in radiation-exposed mice.