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Neuromyelitis optica is an autoimmune inflammatory disorder targeting aquaporin-4 water channels in CNS astrocytes. Histopathological descriptions of astrocytic lesions reported in neuromyelitis optica so far have emphasized a characteristic loss of aquaporin-4, with deposition of IgG and complement and lysis of astrocytes, but sublytic reactions have been underappreciated. We performed a multi-modality study of 23 neuromyelitis optica autopsy cases (clinically and/or pathologically confirmed; 337 tissue blocks). By evaluating astrocytic morphology, immunohistochemistry and AQP4 RNA transcripts, and their associations with demyelinating activity, we documented a spectrum of astrocytopathy in addition to complement deposition, microglial reaction, granulocyte infiltration and regenerating activity. Within advanced demyelinating lesions, and in periplaque areas, there was remarkable hypertrophic astrogliosis, more subtle than astrocytic lysis. A degenerative component was suggested by ‘dystrophic’ morphology, cytoplasmic vacuolation, Rosenthal fibres and associated stress protein markers. The abundance of AQP4 mRNA transcripts in sublytic reactive astrocytes devoid of aquaporin-4 protein supported in vivo restoration following IgG-induced aquaporin-4 endocytosis/degradation. Astrocytic alterations extending beyond demyelinating lesions speak to astrocytopathy being an early and primary event in the evolving neuromyelitis optica lesion. Focal astrocytopathy observed without aquaporin-4 loss or lytic complement component deposition verifies that astrocytic reactions in neuromyelitis optica are not solely dependent on IgG-mediated aquaporin-4 loss or lysis by complement or by IgG-dependent leucocyte mediators. We conclude that neuromyelitis optica reflects a global astrocytopathy, initiated by binding of IgG to aquaporin-4 and not simply definable by demyelination and astrocytic lysis. The spectrum of astrocytic morphological changes in neuromyelitis optica attests to the complexity of factors influencing the range of astrocytic physiological responses to a targeted attack by aquaporin-4-specific IgG. Sublytic astrocytic reactions are no doubt an important determinant of the lesion’s evolution and potential for repair. Pharmacological manipulation of the astrocytic stress response may offer new avenues for therapeutic intervention.

Iridovirus infection has threatened the aquaculture industry worldwide. It has been associated with severe disease and economic losses in fish. In the present study, sixty-two fishes (Sea bream = 50; Sea bass = 3; Mullet = 9) were collected from Damietta and Sharkia Governorates, Egypt during May 2019-September 2020. The clinical signs, gross lesions and histopathological findings were recorded and later confirmed by molecular detection of Iridovirus in different fish species. Besides, isolation of molecularly identified Iridovirus from fish tissues in Vero cell cultures was done. Clinically, the affected fishes become lethargic, exhibit severe anemia, petechiae in the skin and gills. Unilateral hemorrhages in eye and cloudy eye were recorded only in Sea bream fish. Necropsy of the infected fishes revealed congestion of the internal organs, petechial hemorrhages on spleen, liver, kidneys and heart. Necrotic foci on liver were also observed. Histopathological examination revealed congestion of portal veins, cytoplasmic vacuolation with presence of intranuclear eosinophilic inclusion bodies within degenerated hepatocytes. Multifocal necrosis and various degree of inflammation in different fish tissues were observed. Molecularly, the obtained 1000 bp amplicon by PCR confirmed the presence of Iridovirus major capsid protein (MCP) gene with a percentage of 12.1%. It was detected in both fry and market size fish as well as in clinically infected and apparently healthy fish. The molecularly identified virus was able to replicate in Vero cells at 28oC, but not at 37 oC. To our knowledge, this is the first report of Iridovirus isolation in Vero cells and detection in fish within Damietta and Sharkia Governorates, Egypt. Further studies are recommended to investigate its presence on a broader scale with genomic sequence analysis.

Objectives: The post-mortem interval (PMI) refers to the amount of time elapsed between death and discovery of the body. This study aimed to evaluate light microscopic cellular changes in the oral mucosa and identify the potential of this method for predicting PMI. Methods: This prospective study was conducted between July 2016 and January 2018 at the Institute of Dental Sciences, Siksha ‘O’ Anusandhan University, Bhubaneswar, India. A total of 150 post-mortem (including 75 gingival and 75 buccal mucosa samples) and 40 ante-mortem (including 20 gingival and 20 buccal mucosa samples) tissue samples were compared using haematoxylin and eosin, periodic acid-Schiff (PAS) and van Gieson stains. Microscopic changes in the epithelium and connective tissue were categorised according to PMI stage as early (20.5 hours since death). Results: Most epithelial cellular changes occurred early, except for arc-shaped nuclei and epithelial shredding which were intermediate and late changes, respectively. However, microscopic changes in the connective tissue were only observable at ≥12.5 hours. There was a progressive decrease in intensity in van Gieson stains and an increase in intensity in PAS stains as PMI increased. Several microscopic features were found to be significant predictors of PMI including epithelial homogenisation, cytoplasmic vacuolation, nuclear degeneration, arc-shaped nuclei, chromatin clumping, red blood cell clumping and lysis, melanin incontinency, myofibril degeneration, salivary gland acini degeneration and epithelial connective tissue separation (P

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a newly-described adult-onset inflammatory syndrome characterized by vacuoles in myeloid and erythroid precursor cells and somatic mutations affecting methionine-41 (p.Met41) in UBA1. The VEXAS syndrome often overlaps with myelodysplastic syndromes (MDS) with autoimmune disorders (AD). By screening the UBA1 gene sequences derived from MDS patients with AD from our center, we identified one patient with a p.Met41Leu missense mutation in UBA1, who should have been diagnosed as MDS comorbid with VEXAS syndrome. This patient respond poorly to immune suppressive drugs. Patients with MDS and AD who have characteristic vacuoles in myeloid and erythroid precursor cells should be screened for UBA1 mutation, these patients are likely to have VEXAS syndrome and unlikely to improve with immunosuppressive drugs and should be considered for other alternative therapies.

The activated hepatic stellate cells (HSCs) are the major cells that secrete the ECM proteins and drive the pathogenesis of fibrosis in chronic liver disease. Targeting of HSCs by modulating their activation and proliferation has emerged as a promising approach in the development of anti-fibrotic therapy. Sorafenib, a multi-kinase inhibitor has shown anti-fibrotic properties by inhibiting the survival and proliferation of HSCs. In present study we investigated sorafenib induced cytoplasmic vacuolation mediated decreased cell viability of HSCs in dose and time dependent manner. In this circumstance, sorafenib induces ROS and ER stress in HSCs without involvement of autophagic signals. The protein synthesis inhibitor cycloheximide treatment significantly decreased the sorafenib-induced cytoplasmic vacuolation with increasing cell viability. Antioxidant human serum albumin influences the viability of HSCs by reducing sorafenib induced vacuolation and cell death. However, neither caspase inhibitor Z-VAD-FMK nor autophagy inhibitor chloroquine could rescue the HSCs from sorafenib-induced cytoplasmic vacuolation and cell death. Using TEM and ER organelle tracker, we conclude that the cytoplasmic vacuoles are due to ER dilation. Sorafenib treatment induces calreticulin and GPR78, and activates IRE1α-XBP1s axis of UPR pathway, which eventually trigger the non-apoptotic cell death in HSCs. This study provides a notable mechanistic insight into the ER stress directed non-apoptotic cell death with future directions for the development of efficient anti-fibrotic therapeutic strategies.

Acute toxicity (96 h LC50) of phenol was analyzed in the cat fish Mystus vittatus in static bio-assay over a 96-h exposure period using probit method. The 24, 48, 72, and 96 h LC50 values (with 95% confidence limits) of phenol for fingerling catfish were found out as 13.98, 13.17, 12.62, and 12.21 mg/l respectively. Investigations pertaining to the histopathological sections have shown high degree of pathological lesions observed in various parts like gill, liver intestine, and kidney of the fish species. Analysis of gill section revealed observable changes in the experimental species such as fusion, malformation at the tip of secondary lamellae, vacuolation, hyperplasia, and epithelial damage. Exposure of phenol showed cytoplasmic vacuolation, tissue damage, and loss of hepatic cell wall in the liver of experimental organism. Lesions of tissue damage at the epithelial site, inflammation, and clumping of adjacent villi made of columnar epithelium have been observed in the intestine of fish, and also the excretory part of the fish kidney revealed various changes like glomerular atrophy, damage of Bowman's capsule, vacuolization, and degeneration of renal epithelium. The current study on histological changes observed in the experimental organisms has thrown light on the current scenario which poses threat and danger to the whole aquatic ecosystem, and this study plays a vital role in assessing the aquatic pollution.

Paclitaxel is an anticancer drug for the treatment of non-small cell lung cancer (NSCLC). However, drug-resistance remains a major problem. Honokiol is a natural component which has been found to exhibit anti-tumor activity. Paclitaxel and honokiol have been reported to be able to induce paraptosis. The aim of this study was to investigate whether honokiol can reverse paclitaxel resistance by inducing paraptosis in NSCLC cells. NSCLC cell lines H1650 (paclitaxel-sensitive), H1299 and H1650/PTX (intrinsic and acquired paclitaxel-resistant, respectively) were used to assess the cytotoxic effects of paclitaxel and honokiol. Light and transmission electron microscopy were performed to detect cytoplasmic vacuolation. In vitro cell viability and clonogenic survival assays, as well as in vivo xenograft assays were conducted to test synergistic killing effects of paclitaxel and honokiol on NSCLC cells. Western blotting, flow cytometry and immunofluorescence were performed to evaluate paraptosis-regulating mechanisms. We found that combination treatment with paclitaxel and honokiol synergistically killed H1650, H1299 and H1650/PTX cells by inducing paraptosis, which is characterized by cytoplasmic vacuolation. Moreover, paclitaxel/honokiol treatment resulted in a significant growth delay in H1299 xenograft tumors that showed extensive cytoplasmic vacuolation. Mechanistically, proteasomal inhibition-mediated endoplasmic reticulum (ER) stress and unfolded protein responses leading to ER dilation, and the disruption of intracellular Ca2+ homeostasis and mitochondrial Ca2+ overload resulting in mitochondrial disfunction, were found to be involved in paclitaxel/honokiol-induced paraptosis. Cellular protein light chain 3 (LC3) may play an important role in paclitaxel/honokiol induced cytoplasmic vacuolation and NSCLC cell death. Combination of honokiol and paclitaxel may represent a novel strategy for the treatment of paclitaxel-resistant NSCLC.

Silver nanoparticles (Ag NPs) are invested in various sectors and are becoming more persistent in our ambient environment with potential risk on our health and the ecosystems. The current study aims to investigate the histological, histochemical and ultrastructural hepatic changes that might be induced by 10 nm silver nanomaterials. Male mice (BALB/C) were exposed for 35 injections of daily dose of 10 nm Ag NPs (2 mg/kg). Liver tissues were subjected to examination by light and electron microscopy for histological, histochemical and ultrastructural alterations. Exposure to Ag NPs induced Kupffer cells hyperplasia, sinusoidal dilatation, apoptosis, ground glass hepatocytes appearance, nuclear changes, inflammatory cells infiltration, hepatocytes degeneration and necrosis. In addition, 10 nm Ag NPs induced histochemical alterations mainly glycogen depletion with no hemosiderin precipitation. Moreover, these nanomaterials exhibited ultrastructure alterations including mitochondrial swelling and cristolysis, cytoplasmic vacuolation, apoptosis, multilammellar myelin figures formation and endoplasmic destruction and reduction. The findings revealed that Ag NPs can induce alterations in the hepatic tissues, the chemical components of the hepatocytes and in the ultrastructure of the liver. One may also conclude that small size Ag NPs, which are increasingly used in human products could cause various toxigenic responses to all hepatic tissue components.

The current study was undertaken to determine the histopathology and heavy metals content (lead and cadmium) in water and in fish samples caught from the Tigris River in Baghdad. The maximum means of aqueous metals (mg/L) were found at site 3 in the following order: Pb (1.25) > Cd (0.06) followed by site 2 Pb (1.04) > Cd (0.05). The results revealed marked differences (P Cd. The general order of metals levels in different tissues are represented as follows livers > kidneys > muscles > gills. Most common livers lesions observed in Luciobarbus xanthopterus, in the polluted sites were cytoplasmic vacuolation, degeneration, and mononuclear cells infiltration. While kidneys from polluted sites exhibited detached epithelial cells from the basal lamina with hydrobic degeneration. Gills exhibited hyperplasia, lifting and necrosis of the secondary lamellae. These results present a good indicator for bio-monitoring of heavy metals pollution in the Tigris River. Hence, it is very important to make a comprehensive assessment of the hazards posed by these metals in other water bodies of the country.

Introduction: Polychlorinated biphenyl (PCB) is considered one of the environmental pollutants. It is used as hydraulic coils in vacuum pumps, pesticides transformers, heat-exchange systems, capacitors and as additives in adhesive inks, paints, plastics, copying paper and sealants. Alpha lipoic acid (ALA) is an antioxidant substance normally present in mitochondria as a coenzyme. Aim of the Work: To evaluate the protective effect of ALA on PCB induced testicular toxicity. Materials and Methods: Twenty five adult male albino rats were used in this study. They were divided into four groups, a control group included 10 rats, group II rats received alpha lipoic acid 25mg/Kg /day orally for 30 days, group III rats received PCB 5mg /Kg/day orally for 30 days and group IV rats received both PCB and alpha lipoic acid at the same previous dose for 30 days. At the appropriate time, the specimens were taken and prepared for light and electron microscope study. Results: LM examination revealed structural alterations in group III in the form of wide spaces between seminiferous tubules that contain homogeneous acidophilic substance, partial or complete detachment of the tubules from the basement membrane and total distorted irregular shaped tubules. Also dilated congested blood vessels were seen. EM examination of this group revealed Sertoli cells with cytoplasmic vacuolation and dilated rER. The basement membrane appeared as thick and irregular line under Sertoli and spermatogenic cells and it was interrupted in some points. Primary spermatocyte appeared shrunken while others revealed vacuoles in the cytoplasm and perinuclear dilatation. Leydig cells showed irregular vacuoles and swollen destroyed mitochondria. Amelioration of the previous histological changes could be detected in group IV. Conclusion: It could be concluded that alpha-lipoic acid has a protective effect against PCB induced testicular toxicity.

Canine transmissible venereal tumour (CTVT) is a well-documented transplantable tumour in dogs, with no breed or sex predilection and a low metastatic rate. The present short communication reports a case of naturally occurring multicentric TVT in a male dog with a unique cutaneous involvement. A 13-year-old intact male German-Shepherd was presented with multiple nodular lesions disseminated over the face, neck, left forelimb, caudal to left shoulder and abdomen regions. Grossly the lesions were non-fluctuating, nodular, rapidly growing and ulcerated in few growths, measuring up to 2-5 cm in diameter. A rapid and precise diagnosis was made based on fine needle aspiration cytology (FNAC) of nodules and an impression smear of ulcerated lesions. Hematology revealed leucocytosis with marked neutrophilia. FNAC of cutaneous nodule revealed neoplastic population of round cells having characteristic cytoplasmic vacuolation typical of TVT. Based on the anamnesis and cytological examinations the case was diagnosed as primary cutaneous TVT in a progressing growth phase. Chemotherapy with vincristine sulphate resulted in complete resolution of clinical signs and recovery. The effects of the treatment and regression of tumour were also assessed post-therapy by cytology.

Exposure to nanoparticles by various routes results in size-dependent translocation of nanoparticles to the systemic circulation and subsequent accumulation in the liver. The purpose of this study was to determine possible adverse effects in the liver of long-lasting nanoparticle presence in the organ. Mice exposed to a single dose (162 µg/animal equivalent to 9 mg/kg body weight) of TiO2, CeO2 or carbon black nanoparticles by intratracheal instillation or intravenous injection, resulting in relatively low or high liver burdens, were followed for 1, 28 or 180 days. Clinical appearance, feed intake, body and liver weights, hematological indices, and transaminases and alkaline phosphatase activities were unaffected by exposure. Exposure-related foreign material persisted in the liver up to 180 days after intratracheal and intravenous exposure, mainly in sinusoids, near Kupffer cells, or around blood vessels. Increased incidences of histological findings after intratracheal or intravenous exposure included: initially, prominent nuclei of Kupffer cells, the apparent increase in binucleate hepatocytes (TiO2 and carbon black) and inflammatory infiltrations (CeO2), later, cytoplasmic vacuolation, pyknosis and necrosis, especially for CeO2. Thus, neither low nor high nanoparticle burden in the liver affected enzymatic markers of liver injury, but indications of exposure-related necrotic changes, particularly for CeO2 nanoparticles, were noted.

Introduction: Carbimazole is used in the treatment of hyperthyroidism. Parsley is a common herb used in various types of industries such as food, cosmetics, and pharmaceuticals.Aim of the study: The current experiment is aimed to assess the harmful effect of carbimazole on the exocrine part of the pancreas of adult male albino rats and to analyze the protective role of parsley extract. Material and methods: twenty-eight rats were used and divided equally into control group, parsley group that was administered 1 ml of parsley extract /150 g/day for 8 weeks, carbimazole group that was treated with 1.35 mg of carbimazole/Kg/day for 8 weeks, and carbimazole and parsley extract-treated group that received both carbimazole and parsley extract in the same doses and durations as the previous groups. The pancreatic specimens were dissected out and prepared for light and electron microscopic examination.Results: Carbimazole induced clear histopathological alterations in the rat pancreas compared to the control group. There was degeneration in the epithelial cells of pancreatic acini with cytoplasmic vacuolation and a marked decrease in apical acidophilia. Widening in the intercellular space with mononuclear cellular infiltration and blood vessel congestion were also noticed. Morphological analysis showed a significant increase in collagen fibers in-between the pancreatic acini, around the blood vessels, and the interlobular ducts. Ultrastructure analysis also revealed dilatation in the rough endoplasmic reticulum, ballooning mitochondria with disturbed cristae as well as less electron-dense secretory granules. However, carbimazole and parsley extract co-treated showed major improvement in the histology and ultrastructure of pancreatic tissue.In conclusion: the results verified the protective role of parsley against the toxic effect of carbimazole which could belong to the antioxidant properties of parsley.KeywordsCarbimazole; Pancreas; Histopathology; Parsley; ultrastructure

Toosendanin (TSN) is a crucial component from Toosendan Fructus with a promising anti-tumor capacity. It is also the primary suspect hepatotoxic component of Toosendan Fructus. However, the mechanisms underlying TSN-induced liver injury are still largely unknown. In present study, we evaluated the hepatotoxicity of TSN on zebrafish and explored the role of inflammation, autophagy, and apoptosis in TSN-induced hepatotoxicity. We found that TSN treatment decreased the area and fluorescence intensity of zebrafish liver in time- and dose-dependent manners at nonlethal concentrations. The ALT and AST activities were increased after TSN treatment. Severe cytoplasmic vacuolation and nuclear shrank were found in the liver of TSN-treated zebrafish. The expression profile of genes demonstrated that inflammation, autophagy and apoptosis pathways were involved in TSN-induced hepatotoxicity. Our study demonstrated for the first time that TSN treatment gave rise to liver injury in zebrafish, and inflammation, autophagy, apoptosis played a role in TSN-induced hepatotoxicity.

Background Tamiflu (Oseltamivir) and Adamine (Amantadine HCl) are antiviral drugs which are used for prevention and treatment for influenza. The present study was carried out to evaluate the effect of Tamiflu and Adamine on the liver of adult male albino mice from the histological and ultrastructural points of views. Results Histological examination of liver sections treated with Tamiflu and Adamine included enlargement and congestion of central and hepatic veins in addition to erosion of their endothelial lining cells, cytoplasmic vacuolation of hepatocytes, pyknosis of their nuclei, and dilatation of hepatic sinusoid. The electron microscopic investigation illustrated mitochondrial swelling, fragmented rough endoplasmic reticulum, cytoplasmic vacuolation, the nuclei with irregular envelope and condensed heterochromatin, dilated microvilli in sinusoid, in addition to active Kupffer cells have many lysosomes and filopodia in its membrane. Conclusion The study suggested that both drugs induced histopathological and ultrastructural alterations in hepatic tissue. In conclusion, Tamiflu and Adamine have pathological effects on liver of albino mice (Mus musculus).

Introduction: Silver nanomaterials; the engineered nanomaterials; have many industrial applications. They are used in manufacture of cosmetic and daily used products as food and clothes. Nanoparticles can pass through different biological body barriers, accumulate in the female reproductive organs as uterus and ovaries and exert their toxicity.Aim of the work: to evaluate the effect of silver nanoparticles on the histological structure of the endometrium using different histological and immunohistochemical techniques.Materials and methods: thirty-six adult female albino rats were divided into three equal groups; group I (control group), group II and group III. Silver nanoparticles were administered daily for 2 weeks at dose 30mg /kg and 300mg/kg respectively orally to group II and III. The size of the used nanoparticles is 20 nm. Specimens of uterus were taken to be processed for examination by light microscope (haematoxylin and eosin, Masson trichrome and TNF- alpha immunohistochemical staining) and transmission electron microscope.Results: AgNps-treated animals showed stratification, cytoplasmic vacuolation, discontinuation and desquamation in endometrial epithelial cells. The lamina propria showed cellular infiltration (inflammatory reaction), empty spaces and increase the deposition of collagen fibers (fibrosis). Ultrastructurally, they showed focal loss of the apical microvilli of the endometrial epithelial cells, apical cytoplasmic vacuoles, swollen, distorted and irregularly arranged mitochondria and large amount of secondary lysosomes and autophagic vacuoles. Focal separation of the epithelial cells with destruction of the intercellular junctions was seen. The lamina propria showed accumulation of collagen fibres and eosinophilic infiltration. Immunohistochemical study revealed highly significant increase in the TNF- alpha immunoexpression particularly in group III. All these changes were more severe in animals with high dose than those of low dose.Conclusion: silver nanoparticles induce structural changes in a dose dependent manner in the endometrium. So, it should be given cautiously to females to avoid uterine damage.

Covert mortality nodavirus (CMNV) is an alphanodavirus mainly infecting marine shrimp and co-inhabiting organisms in aquaculture ponds. To evaluate the possibility of CMNV prevalence in the wild fish species, epidemiological survey of CMNV infection in Larimichthys polyactis, the dominant species in the Yellow Sea and East China Sea, were conducted in the present study. We performed CMNV RT-LAMP assay in samples of L. polyactis collected in August 2018 and 2019 and found that CMNV prevalence was 18% and 7%, respectively. The nucleotide sequences of both RdRp and capsid protein genes of CMNV from L. polyactis were 99% similar to those of CMNV isolated from shrimp. CMNV-positive L. polyactis exhibited necrosis of cardiac muscle, oocytes loosely arranging, severe cytoplasmic vacuolation of hepatocytes, moderate pyknosis of brain pyramidal cells, degenerate renal tubular cells with ill-defined margins, and declined spleen cells in the histological examination. Moreover, CMNV-positive signals were further observed in pyramidal cells of the brain, the cortical area of the kidney, oocyte growth rings, and in necrotic tissues of cardiac muscle, liver, and spleen in the in situ hybridization assay. The results revealed that CMNV had colonized in the wild populations of L. polyactis and the ecological risk of CMNV spread and epidemic in wild fish in the coastal water was non-negligible.

Platycodin D (PD) is a major active component of the roots of Platycodon grandiflorum (Jacq.) A.DC. and possesses multiple biological and pharmacological properties, including anti-cancer activity. The aim of this study was to characterize PD-induced cytoplasmic vacuolation in human cancer cells and investigate the underlying mechanisms. PD-induced cancer cell death was associated with cytoplasmic pinocytic and autophagic vacuolation. Cellular energy levels were decreased by this compound, leading to the activation of AMP-activated protein kinase (AMPK). Additionally, compound C, an inhibitor of AMPK, completely prevented PD-induced vacuolation. These results suggest that PD induces cancer cell death, associated with excessive vacuolation through AMPK activation when cellular energy levels are low. Therefore, our findings provide a mechanistic rationale for a novel combinatorial approach using PD to treat cancer.

The present study was designed to assess the adverse effects of the agrochemical Almix on comparative basis in gill, liver and kidney of Heteropneustes fossilis through histological and ultrastructural observations under field (8 g/acre) and laboratory (66.67 mg/L) conditions. Exposure duration of both experiments was 30 days. Gill showed atrophy in secondary lamellae, hypertrophied gill epithelium, damage in chloride and pillar cells, and detachment of chloride cells from gill epithelium under laboratory condition, but hypertrophy in gill epithelium and fusion in secondary lamellae were seen under field condition. In gill, scanning electron microscopy (SEM) showed fragmentation in microridges, hyper-secretion of mucus and loss of normal array in microridges, while transmission electron microscopy (TEM) displayed dilated mitochondria and rough endoplasmic reticulum (RER), abnormal sized vacuolation in chloride cells under laboratory condition. In liver, hypertrophied and pyknotic nuclei, disarrangement of hepatic cords, and cytoplasmic vacuolation were prominent under laboratory study but in field condition the liver showed little alterations. TEM study showed severe degeneration in RER and mitochondria and cytoplasmic vacuolation under laboratory condition but dilated mitochondria were prominent in field observation. Kidney showed severe nephropathic effects including degenerative changes in proximal and distal convolute tubule, damage in glomerulus under light microscopy, while deformity in nucleus, fragmentation in RER, severe vacuolation and necrosis in kidney were prominent under TEM study. The results clearly demonstrated that responses were more prominent in laboratory than field study. Thus the responses displayed by different tissues of concerned fish species exposed to Almix could be considered as indications of herbicide toxicity in aquatic ecosystem.

Background: Repeated heating of vegetable oils especially palm oil that is commonly and commercially used in frying of food at homes and restaurants has been investigated for its risks on health status. It seemed to carry potential hazards on the liver tissue. Aim: To investigate the impact of eating foods fried with 5-times heated palm oil on liver of adult male rats for 8 weeks and the possibility of recovery of histomorphometric changes after stoppage of use of reheated palm oil for additional 4 weeks.Material and Methods: Thirty adult male albino rats were divided equally into 3 groups; control group (received normal balanced diet for 8 weeks), H5 group (received 5-times heated palm oil enriched diet for 8 weeks) and Recovery group (received five times heated palm oils for 8 weeks and then left on balanced diet for another 4 weeks). At the end of the experiment, animals were anesthetized with ether then sacrificed. Specimens taken from the liver were processed for histological evaluation. Morphometric studies were conducted and collected data undergone statistical analysis.Results: Histological examination showed alterations in liver tissue of H5 group including fat droplets, mononuclear cellular infiltration, dilatation of central vein and blood sinusoids, collagen deposition and degeneration and necrosis of hepatocytes. Ultrastructural examination showed lipid droplets, irregular mitochondria, cytoplasmic vacuolation, irregular nuclear envelop and dilatation of endoplasmic reticulum. Recovery group showed decreased lipid droplets, less dilatation and congestion of central vein and blood sinusoids, decreased inflammatory cells but few hepatocytes still show degeneration. Ultrastructure of hepatocytes of recovery group became more or less normal with restoration of cytoplasmic organelles. Morphometric results support the histological findings.Conclusion: Consumption of repeatedly heated palm oil is injurious to the liver tissue, and those injuries show possible recovery after stoppage of its consumption.

6:2 Cl-PFESA is a polyfluoroalkyl ether with high environmental persistence that has been confirmed to have significant adverse effects on animals. In this study, 6-week-old female C57BL/6 mice were exposed to 0, 1, 3 and 10 μg/L 6:2 Cl-PFESA for 10 weeks to estimate the hepatotoxicity of 6:2 Cl-PFESA and explore its underlying molecular mechanism. The results indicated that 6:2 Cl-PFESA preferentially bioaccumulated in the liver and induced hepatic cytoplasmic vacuolation and hepatomegaly in mice. In addition, serum metabolic profiling showed that 6:2 Cl-PFESA exposure caused an abnormal increase in amino acids and an abnormal decrease in acyl-carnitine, which interfered with fatty acid transport and increased the risk of metabolic diseases. Further experiments showed that 6:2 Cl-PFESA formed more hydrogen bonds with PPAR-γ than PFOS, Rosi and GW9662, and the binding affinity of 6:2 Cl-PFESA toward PPAR-γ was the highest among the ligands. 6:2 Cl-PFESA promoted the differentiation of 3T3-L1 cells by increasing PPAR-γ expression. Therefore, our results showed that 6:2 Cl-PFESA has the potential to induce liver damage and dysfunction in female mice, and this effect was achieved through PPAR-γ. This study is the first to reveal the hepatic toxicity of 6:2 Cl-PFESA in female mammals and provides new insights for subsequent in-depth research.

Introduction: Potassium bromate (KBrO3) is an oxidizing agent that is widely used as a flour improver. However, it induces genotoxic and carcinogenic effects on different body organs in a dose and duration-dependent manner. So, the aim of this study was: to explore the effects of KBrO3 on the structure of the rat jejunal mucosa and investigate the potential role of lycopene, a strong antioxidant molecule, in preventing or ameliorating the effect of KBrO3. Materials & Methods: Twenty-four adult male albino rats were used and divided equally into four experimental groups; control group, lycopene group that received 10mg of lycopene/kg/day/orally; KBrO3 group that received 100mg of KBrO3/kg/day/ orally and KBrO3 and lycopene group that received KBrO3 and lycopene in the same doses as in the previous groups. Animals were sacrificed after 4 weeks and the specimens from the jejunum were processed for histological, immunohistochemical, and ultrastructural examinations. Results: the jejunal mucosa of the KBrO3 treated group showed short and broad villi, discontinuity and desquamation of their lining epithelial cells, inflammatory cellular infiltration, and dilatation of the blood vessels. Moreover, there was a significant decrease in the number of goblet cells and PCNA immuno-stained nuclei in the jejunum. Ultramicroscopic examination showed swollen vacuolated mitochondria, dilated rough endoplasmic reticulum, and shrunken dark nuclei. Interestingly, the group treated with both lycopene and KBrO3 showed less cytoplasmic vacuolation and mitochondrial abnormalities in the epithelial cells lining the villi. Furthermore, there was a significant improvement in the height of jejunal villi, the number of goblet cells, and PCNA immuno-stained nuclei. In conclusion: KBrO3 induced cellular damage in the rat jejunal mucosa which was prevented by coadministration of lycopene.

Samples from eight species of corals (Colpophyllia natans, Dendrogyra cylindrus, Diploria labyrinthiformis, Meandrina meandrites, Montastraea cavernosa, Orbicella faveolata, Pseudodiploria strigosa, and Siderastrea siderea) that exhibited gross clinical signs of acute, subacute, or chronic tissue loss attributed to stony coral tissue loss disease (SCTLD) were collected from the Florida Reef Tract during 2016–2018 and examined histopathologically. The hallmark microscopic lesion seen in all eight species was focal to multifocal lytic necrosis (LN) originating in the gastrodermis of the basal body wall (BBW) and extending to the calicodermis, with more advanced lesions involving the surface body wall. This was accompanied by other degenerative changes in host cells such as mucocyte hypertrophy, degradation and fragmentation of gastrodermal architecture, and disintegration of the mesoglea. Zooxanthellae manifested various changes including necrosis (cytoplasmic hypereosinophilia, pyknosis); peripheral nuclear chromatin condensation; cytoplasmic vacuolation accompanied by deformation, swelling, or atrophy; swollen accumulation bodies; prominent pyrenoids; and degraded chloroplasts. Polyhedral intracytoplasmic eosinophilic periodic acid–Schiff-positive crystalline inclusion bodies (∼1–10 μm in length) were seen only in M. cavernosa and P. strigosa BBW gastrodermis in or adjacent to active lesions and some unaffected areas (without surface lesions) of diseased colonies. Coccoidlike or coccobacilloidlike structures (Gram-neutral) reminiscent of microorganisms were occasionally associated with LN lesions or seen in apparently healthy tissue of diseased colonies along with various parasites and other bacteria all considered likely secondary colonizers. Of the 82 samples showing gross lesions of SCTLD, 71 (87%) were confirmed histologically to have LN. Collectively, pathology indicates that SCTLD is the result of a disruption of host–symbiont physiology with lesions originating in the BBW leading to detachment and sloughing of tissues from the skeleton. Future investigations could focus on identifying the cause and pathogenesis of this process.

FTY720, a sphingosine-1-phosphate (S1P) receptor modulator, is a synthetic compound produced by the modification of a metabolite from I. sinclairii. Here, we found that FTY720 induced non-apoptotic cell death in human glioma cells (U251MG, U87MG, and U118MG). FTY720 (10 &micro, M) dramatically induced cytoplasmic vacuolation in glioma cells. However, FTY720-mediated vacuolation and cell death are not associated with autophagy. Genetic or pharmacological inhibition of autophagy did not inhibit FTY720-induced cell death. Herein, we detected that FTY720-induced cytoplasmic vacuoles were stained with lysotracker red, and FTY720 induced lysosomal membrane permeabilization (LMP). Interestingly, cathepsin inhibitors (E64D and pepstatin A) and ectopic expression of heat shock protein 70 (HSP70), which is an endogenous inhibitor of LMP, markedly inhibited FTY720-induced cell death. Our results demonstrated that FTY720 induced non-apoptotic cell death via the induction of LMP in human glioma cells.

This study evaluated the synergistic anti-cancer potential of cannabinoid combinations across the MDA-MB-231 and MCF-7 human breast cancer cell lines. Cannabinoids were combined and their synergistic interactions were evaluated using median effect analysis. The most promising cannabinoid combination (C6) consisted of tetrahydrocannabinol, cannabigerol (CBG), cannabinol (CBN), and cannabidiol (CBD), and displayed favorable dose reduction indices and limited cytotoxicity against the non-cancerous breast cell line, MCF-10A. C6 exerted its effects in the MCF-7 cell line by inducing cell cycle arrest in the G2 phase, followed by the induction of apoptosis. Morphological observations indicated the induction of cytoplasmic vacuolation, with further investigation suggesting that the vacuole membrane was derived from the endoplasmic reticulum. In addition, lipid accumulation, increased lysosome size, and significant increases in the endoplasmic reticulum chaperone protein glucose-regulated protein 78 (GRP78) expression were also observed. The selectivity and ability of cannabinoids to halt cancer cell proliferation via pathways resembling apoptosis, autophagy, and paraptosis shows promise for cannabinoid use in standardized breast cancer treatment.

Bhasmas are Ayurvedic herbo-mineral formulations that have been used since ancient times for therapeutic benefits. Godanti Bhasma (GB) is an anhydrous calcium sulfate preparation processed by heating of gypsum powder with herbal extracts. Thermo-transformation of gypsum into the anhydrous GB was confirmed by Raman and FT-IR spectroscopy. GB particle showed size range of 0.5-5 µm and neutral surface charge. Exposure to mammalian cells with GB particles showed massive vacuolation in their cytoplasm. Interestingly, no vacuolation was observed with parent gypsum particle. The result indicated that the cytoplasmic vacuolation by GB was due to its unique physicochemical property obtained during the thermo-transformation of gypsum. Using lysosomal inhibitors Bafilomycin A1 (BFA1) and Chloroquine (CQ), the process of vacuole formation was suppressed indicating GB induced vacuolation require acidic environment. The GB induced vacuolation was also found to follow dose and time dependent manner. Vacuolation often accompany with the sign of cell death whereas, in our study, massive vacuolation by GB did not induce any cell death. Moreover, GB treated cells survive with massive vacuolar process, which was reversed following post-treatment with vacuole inhibitors in GB treated cells, suggesting normal vacuolar function is essential for cell survival. Treatment of cells with GB was also found to induce translocation of LC3 protein from the nucleus to vacuolar membrane, indicating LC3 associated phagocytosis (LAP) is involved in the vacuolar process. Interestingly, the LAP function was found to be reversed in the cells treated with vacuole inhibitors. Our results provide a mechanistic correlation with GB induced vacuolation and associated LAP function, essential for cell survival.Abstract Figure

The present study analyzed the effects of different concentrations of Acmella oleracea crude ethanolic extract (EEAO) on the development of germ cells from semi-engorged Amblyomma cajennense females in order to evaluate the potential of this natural chemical as a strategy to control these important ectoparasites. A hundred semi-engorged females were divided into five groups (duplicates) (10 animals/group): Control 1 (distilled water); Control 2 (solvent ethanol 50% and DMSO 1%); and Treatment I to III (3.1, 6.2, and 12.5 mg/mL of EEAO, respectively). For the exposure of the ticks to the extract was used the Adult Immersion Test. After the exposition, the ovaries were removed and submitted to histological analysis using Harris hematoxylin and aqueous eosin. The histochemical tests were performed using PAS and Bromophenol blue staining techniques, for the detection of total polysaccharides and total protein, respectively. The extract caused significant alterations in the oocytes, including changes in the shape of the cells, disorganization, and cytoplasmic vacuolation, decrease in the number of yolk granules and germ vesicle fragmentation. These alterations were more intense in the oocytes in initial developmental stages (I and II). The results obtained in this study confirm the cytotoxic potential of the ethanolic extract of A. oleracea on the germ cells of A. cajennense females, opening up the possibility to use this extract as an alternative to control these ectoparasites.