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Diseases (Basel, Switzerland) Jun 2023Oxymetholone is one of the anabolic steroids that has widely been used among teenagers and athletes to increase their muscle bulk. It has undesirable effects on male...
Oxymetholone is one of the anabolic steroids that has widely been used among teenagers and athletes to increase their muscle bulk. It has undesirable effects on male health and fertility. In this study, the therapeutic effects of platelet-rich plasma (PRP) on oxymetholone-induced testicular toxicity were investigated in adult albino rats. During the experiments, 49 adult male albino rats were divided into 4 main groups: Group 0 (donor group) included 10 rats for the donation of PRP, Group I (control group) included 15 rats, Group II included 8 rats that received 10 mg/kg of oxymetholone orally, once daily, for 30 days, and Group III included 16 rats and was subdivided into 2 subgroups (IIIa and IIIb) that received oxymetholone the same as group II and then received PRP once and twice, respectively. Testicular tissues of all examined rats were obtained for processing and histological examination and sperm smears were stained and examined for sperm morphology. Oxymetholone-treated rats revealed wide spaces in between the tubules, vacuolated cytoplasm, and dark pyknotic nuclei of most cells, as well as deposition of homogenous acidophilic material between the tubules. Electron microscopic examination showed vacuolated cytoplasm of most cells, swollen mitochondria, and perinuclear dilatation. Concerning subgroup IIIa (PRP once), there was a partial improvement in the form of decreased vacuolations and regeneration of spermatogenic cells, as well as a reasonable improvement in sperm morphology. Regarding subgroup IIIb (PRP twice), histological sections revealed restoration of the normal testicular structure to a great extent, regeneration of the spermatogenic cells, and most sperms had normal morphology. Thus, it is recommended to use PRP to minimize structural changes in the testis of adult albino rats caused by oxymetholone.
PubMed: 37366872
DOI: 10.3390/diseases11020084 -
MBio Jun 2017Many viruses migrate between different cellular compartments for successive stages of assembly. The HSV-1 capsid assembles in the nucleus and then transfers into the...
Many viruses migrate between different cellular compartments for successive stages of assembly. The HSV-1 capsid assembles in the nucleus and then transfers into the cytoplasm. First, the capsid buds through the inner nuclear membrane, becoming coated with nuclear egress complex (NEC) protein. This yields a primary enveloped virion (PEV) whose envelope fuses with the outer nuclear membrane, releasing the capsid into the cytoplasm. We investigated the associated molecular mechanisms by isolating PEVs from US3-null-infected cells and imaging them by cryo-electron microscopy and tomography. (pUS3 is a viral protein kinase in whose absence PEVs accumulate in the perinuclear space.) Unlike mature extracellular virions, PEVs have very few glycoprotein spikes. PEVs are ~20% smaller than mature virions, and the little space available between the capsid and the NEC layer suggests that most tegument proteins are acquired later in the egress pathway. Previous studies have proposed that NEC is organized as hexamers in honeycomb arrays in PEVs, but we find arrays of heptameric rings in extracts from US3-null-infected cells. In a PEV, NEC contacts the capsid predominantly via the pUL17/pUL25 complexes which are located close to the capsid vertices. Finally, the NEC layer dissociates from the capsid as it leaves the nucleus, possibly in response to pUS3-mediated phosphorylation. Overall, nuclear egress emerges as a process driven by a program of multiple weak interactions. On its maturation pathway, the newly formed HSV-1 nucleocapsid must traverse the nuclear envelope, while respecting the integrity of that barrier. Nucleocapsids (125 nm in diameter) are too large to pass through the nuclear pore complexes that conduct most nucleocytoplasmic traffic. It is now widely accepted that the process involves envelopment/de-envelopment of a key intermediate-the primary enveloped virion. In wild-type infections, PEVs are short-lived, which has impeded study. Using a mutant that accumulates PEVs in the perinuclear space, we were able to isolate PEVs in sufficient quantity for structural analysis by cryo-electron microscopy and tomography. The findings not only elucidate the maturation pathway of an important human pathogen but also have implications for cellular processes that involve the trafficking of large macromolecular complexes.
Topics: Animals; Capsid; Capsid Proteins; Cell Nucleus; Chlorocebus aethiops; Cryoelectron Microscopy; Herpesvirus 1, Human; Nuclear Envelope; Phosphorylation; Vero Cells; Viral Proteins; Virion; Virus Assembly; Virus Release
PubMed: 28611252
DOI: 10.1128/mBio.00825-17 -
Journal of Ethnopharmacology Jun 1987Gossypol acetic acid (GAA) at the dosage of 30 mg/kg daily for 2 weeks could prolong the sleeping time of pentobarbital, increase the SGPT level, decrease the liver...
Gossypol acetic acid (GAA) at the dosage of 30 mg/kg daily for 2 weeks could prolong the sleeping time of pentobarbital, increase the SGPT level, decrease the liver concentration of cytochrome P-450 and GSH content, inhibit the activity of cytochrome C reductase and aminopyrine-N-demethylase, but was without effect on cytochrome b5 and aniline hydroxylase. At a smaller daily dosage (15 mg/kg for 4 weeks), GAA could induce the rise of SGPT level and GSH content without affecting the liver metabolizing enzymes. GAA at both dosages could induce marked pathological changes of liver cells in treated rats, such as vacuolation of mitochondria, dilation of endoplasmic reticulum and widening of perinuclear space as well as proliferation of collagen fibers in Disse's spaces. GAA could induce the formation of O2 and H2O2 and could inhibit Ca2+ sequestration in rat liver microsomes in vitro. [C14]-gossypol could bind to microsomal protein irreversibly either in the presence or absence of NADPH. It may be concluded that GAA is capable of causing damage to liver cells.
Topics: Animals; Calcium; Cell Membrane Permeability; Chemical and Drug Induced Liver Injury; Gossypol; Lipid Peroxides; Liver; Male; Microscopy, Electron; Rats; Rats, Inbred Strains
PubMed: 3626595
DOI: 10.1016/0378-8741(87)90119-x -
Viruses Jan 2015Herpes simplex virus 1 (HSV-1) capsids are assembled in the nucleus bud at the inner nuclear membrane into the perinuclear space, acquiring envelope and tegument. In...
Herpes simplex virus 1 (HSV-1) capsids are assembled in the nucleus bud at the inner nuclear membrane into the perinuclear space, acquiring envelope and tegument. In theory, these virions are de-enveloped by fusion of the envelope with the outer nuclear membrane and re-enveloped by Golgi membranes to become infective. Us3 enables the nucleus to cytoplasm capsid translocation. Nevertheless, Us3 is not essential for the production of infective progeny viruses. Determination of phenotype distribution by quantitative electron microscopy, and calculation per mean nuclear or cell volume revealed the following: (i) The number of R7041(∆US3) capsids budding at the inner nuclear membrane was significantly higher than that of wild type HSV-1; (ii) The mean number of R7041(∆US3) virions per mean cell volume was 2726, that of HSV-1 virions 1460 by 24 h post inoculation; (iii) 98% of R7041(∆US3) virions were in the perinuclear space; (iv) The number of R7041(∆US3) capsids in the cytoplasm, including those budding at Golgi membranes, was significantly reduced. Cell associated R7041(∆US3) yields were 2.37×10(8) and HSV-1 yields 1.57×10(8) PFU/mL by 24 h post inoculation. We thus conclude that R7041(∆US3) virions, which acquire envelope and tegument by budding at the inner nuclear membrane into the perinuclear space, are infective.
Topics: Animals; Capsid; Cell Nucleus; Chlorocebus aethiops; Cytoplasm; Gene Deletion; Herpesvirus 1, Human; Microscopy, Electron; Protein Serine-Threonine Kinases; Vero Cells; Viral Load; Viral Proteins; Virion; Virus Assembly; Virus Release
PubMed: 25588052
DOI: 10.3390/v7010052 -
Annals of Anatomy = Anatomischer... Jul 2019Specific ultrastructural anatomy of masticatory muscles is commonly referred to a general pattern assigned to striated muscles. Junctional feet consisting of calcium...
Specific ultrastructural anatomy of masticatory muscles is commonly referred to a general pattern assigned to striated muscles. Junctional feet consisting of calcium channels of the sarcoplasmic reticulum (i.e. the ryanodine receptors, RyRs) physically connected to the calcium channels of the t-tubules build triads within striated muscles. Functional RyRs were demonstrated in the nuclear envelopes of pancreas and of a skeletal muscle derived cell line, but not in muscle in situ. It was hypothesized that ryanodine receptors (RyRs) could also exist in the nuclear envelope in the masseter muscle, thus aiming at studying this by transmission electron microscopy. There were identified paired and consistent subsarcolemmal clusters of mitochondria, appearing as outpockets of the muscle fibers, usually flanking an endomysial microvessel. It was observed on grazing longitudinal cuts that the I-band-limited mitochondria were not strictly located in a single intermyofibrillar space but continued transversally over the I-band to the next intermyofibrillar space. It appeared that the I-band-limited transverse mitochondria participate with the column-forming mitochondria in building a rather incomplete mitochondrial reticulum of the masseter muscle. Subsarcolemmal nuclei presented nuclear envelope-associated RyRs. Moreover, t-tubules were contacting the nuclear envelope and they were seemingly filled from the perinuclear space. This could suggest that nucleoplasmic calcium could contribute to balance the cytosolic concentration via pre-built anatomical routes: (i) indirectly, via the RyRs of the nuclear envelope and (ii) directly via the communication of t-tubules and sarcoplasmic reticulum through the perinuclear space.
Topics: Animals; Calcium; Cell Nucleus; Male; Masseter Muscle; Microscopy, Electron, Transmission; Microvessels; Mitochondria; Models, Animal; Muscle Fibers, Skeletal; Myofibrils; Nuclear Envelope; Rabbits; Sarcolemma; Sarcomeres
PubMed: 31117003
DOI: 10.1016/j.aanat.2019.05.006 -
Pflugers Archiv : European Journal of... Nov 2010Patch-clamp recording from the nuclear envelope of a variety of cells has revealed the presence of large-conductance ion channels. It has been argued that these channels...
Patch-clamp recording from the nuclear envelope of a variety of cells has revealed the presence of large-conductance ion channels. It has been argued that these channels are the channels of the nuclear pore complex for passive nucleo-cytoplasmic diffusion. Here we studied spontaneously active large-conductance ion channels in the nuclear envelope of cerebellar Purkinje neurons. These channels were selective for small monovalent cations and demonstrated clear voltage dependence. The channels recorded from the outer nuclear membrane were inhibited by positive potentials whereas the channels from the inner nuclear membrane were inhibited by negative potentials in the patch pipette. These data are compatible with the localization of the channels to the nuclear membrane. We conclude that these channels are not a part of the nuclear pore complex but provide a route for exchange of monovalent cations between the perinuclear space and the cytoplasm and the nucleoplasm.
Topics: Animals; Central Nervous System; Large-Conductance Calcium-Activated Potassium Channels; Male; Neurons; Nuclear Envelope; Patch-Clamp Techniques; Purkinje Cells; Rats; Rats, Wistar
PubMed: 20886229
DOI: 10.1007/s00424-010-0882-5 -
Endocrine Oct 2011Sloan-Kettering virus gene product (Ski) is an unique nuclear pro-oncoprotein and belongs to the ski/sno proto-oncogene family. Ski plays multiple roles in a variety of...
Sloan-Kettering virus gene product (Ski) is an unique nuclear pro-oncoprotein and belongs to the ski/sno proto-oncogene family. Ski plays multiple roles in a variety of cell types, it can induce both oncogenic transformation and terminal muscle differentiation when expressed at high levels. Ski/SnoN are important transcription regulators of the transforming growth factor-β (TGF-β) superfamily and function mainly through heterodimers. Since TGF-β superfamily are key regulators of follicle development and it has been previously shown that SnoN is also vital to follicle development, this research was conducted to clarify the relationship between Ski expression and mouse follicular development, in ovaries of neonatal and gonadotropin-induced immature mice by immunohistochemical and real-time PCR techniques. In postnatal mice, positive staining for Ski was highly detected in oocyte nuclei at postnatal day 1. With follicular development, the localization moved gradually from oocyte nuclei to perinuclear space and the total levels decreased. During the estrous cycle, Ski expression was apparent at proestrus and estrus, faint at metestrus, highest at diestrus. After injection of gonadotropin, Ski was found in perinuclear space and weak in oocyte nuclei. Following the initiation of luteinization, the expression of Ski was found in corpus luteum. Real-time PCR results also showed that Ski mRNA expression was opposite to ovulation-related genes during the cumulus expansion, with the development of the follicles, its expression level decreased. Ski is expressed in a specific manner during follicle development, ovulation and luteinization. So Ski might play essential roles in these processes especially during early follicular development.
Topics: Animals; Animals, Newborn; Cell Nucleus; Chorionic Gonadotropin; Corpus Luteum; DNA-Binding Proteins; Estrous Cycle; Female; Gene Expression Regulation, Developmental; Luteinization; Mice; Mice, Inbred Strains; Oocytes; Oogenesis; Organ Specificity; Ovarian Follicle; Ovulation; Protein Transport; Proto-Oncogene Proteins; RNA, Messenger; Sexual Maturation
PubMed: 21544517
DOI: 10.1007/s12020-011-9477-y -
Acta Histochemica Et Cytochemica Jun 2022Epithelial protein lost in neoplasm (EPLIN) is an actin-associated cytoskeletal protein that plays an important role in epithelial cell adhesion. EPLIN has two isoforms:...
Epithelial protein lost in neoplasm (EPLIN) is an actin-associated cytoskeletal protein that plays an important role in epithelial cell adhesion. EPLIN has two isoforms: EPLINα and EPLINβ. In this study, we investigated the role of EPLINβ in osteoblasts using EPLINβ-deficient ( ) mice. The skeletal phenotype of mice is indistinguishable from the wildtype (WT), but bone properties and strength were significantly decreased compared with WT littermates. Histomorphological analysis revealed altered organization of bone spicules and osteoblast cell arrangement, and decreased alkaline phosphatase activity in mouse bones. Transmission electron microscopy revealed wider intercellular spaces between osteoblasts in mice, suggesting aberrant cell adhesion. In osteoblasts, α- and β-catenins and F-actin were observed at the cell membrane, but OB-cadherin was localized at the perinuclear region, indicating that cadherin-catenin complexes were not formed. EPLINβ knockdown in MC3T3-e1 osteoblast cells showed similar results as in calvaria cell cultures. Bone formation markers, such as , , , and mRNA were reduced in EPLINβ knockdown cells, suggesting an important role for EPLINβ in osteoblast formation. In conclusion, we propose that EPLINβ is involved in the assembly of cadherin-catenin complexes in osteoblasts and affects bone formation.
PubMed: 35821749
DOI: 10.1267/ahc.22-00027 -
The Journal of Biophysical and... Apr 1961Ameloblasts from different regions of upper incisors of rats were examined with the electron microscope. During matrix formation, the cells resemble secretory cells....
Ameloblasts from different regions of upper incisors of rats were examined with the electron microscope. During matrix formation, the cells resemble secretory cells. They are extremely long, tightly packed, and show considerable polarity. Nuclei are at the basal end of the cell. Mitochondria are proximal and the Golgi apparatus distal to the nucleus. Ergastoplasm is found in all levels but mainly in the distal end. A terminal bar apparatus separates the distal end of the cell from Tomes's process. Next to this is soft enamel. The next incisal region is a transitional zone in which the ameloblasts separate easily from the enamel. Endoplasmic reticulum is dilated and very obviously in communication with the perinuclear space. Mitochondria are present not only proximal, but also distal, to the nucleus. The next incisal zone consists of cells related to the maturation of enamel. They no longer resemble secretory cells, but now have more characteristics of transporting cells. Processes from the distal end of the cell are present with mitochondria closely applied to the base of the processes. A considerable amount of intercellular space exists with microvilli projecting into the space. Iron granules appear in these cells, and the ergastoplasmic cisternae are dilated. In the incisal end of this zone, the iron granules form aggregates. The iron finally leaves the cells to enter the enamel. Free RNP particles and fibrils become more evident after the iron leaves the cells. In the most incisal region, the ameloblasts are further reduced in height. Distal processes are no longer present and fibrils are more conspicuous.
Topics: Ameloblasts; Animals; Cell Nucleus; Cytoplasmic Granules; Dental Enamel; Endoplasmic Reticulum; Extracellular Matrix; Golgi Apparatus; Incisor; Microvilli; Mitochondria; Rats
PubMed: 13740699
DOI: 10.1083/jcb.9.4.825 -
Acta Biologica Hungarica Sep 2007The aim of this study was to determine effects of Cd on the structure of ovary, oviduct and uterus after an experimental administration. Animals were divided into three...
The aim of this study was to determine effects of Cd on the structure of ovary, oviduct and uterus after an experimental administration. Animals were divided into three groups. In group A rabbits received cadmium i.p. and were killed after 48 h. In group C Cd was administered p.o. for 5 month. The group K was the control. Decreased relative volume of growing follicles and increased stroma after Cd administration were detected. The number of atretic follicles was significantly higher after administration of Cd. The most frequent ultrastructural alterations observed were undulation of external nuclear membrane, dilatation of perinuclear cistern and endoplasmic reticulum. In all studied types of cells mitochondria with altered structure were found. In the oviduct the highest amount of epithelium in the group with long-term Cd administration was found. Microscopic analysis showed oedematization of the oviduct tissue, caused by disintegration of the capillary wall. An electron microscopic analysis showed dilatation of perinuclear cistern. The intercellular spaces were enlarged and junctions between cells were affected. Mainly after a long-term cadmium administration nuclear chromatin disintegration was present. In the uterus a significant change was determined in the relative volume of glandular epithelium. Increase of stroma was a sign of uterus oedamatization caused by damage in the wall of blood vessels and subsequent diapedesis. After Cd administration alteration in uterus were less expressed, in comparison with ovary and oviduct. Alteration of nuclear chromatin contain following Cd administration suggests degenerative functional changes.
Topics: Animals; Cadmium; Dose-Response Relationship, Drug; Endoplasmic Reticulum; Female; Mitochondria; Nuclear Envelope; Ovarian Follicle; Ovary; Oviducts; Rabbits; Uterus
PubMed: 17899786
DOI: 10.1556/ABiol.58.2007.3.5