Acute renal failure (ARF) is a sudden, significant, and often reversible decline in kidney function, with 25% of all hospital-administered pharmaceuticals potentially causing nephrotoxicity. The study investigates the effectiveness of a novel nanoparticle (NP) formulation of glutathione (GSH) and Lepidium sativum (LS) in improving therapeutic outcomes in a rat model of ARF. Sixty adult male albino rats were allocated into ten groups, comprising six rats each, for the study. ARF was created by daily gentamicin (GN) administration for seven consecutive days and various treatment protocols, including chitosan (CS) NPs, spanlastics NPs, as well as conventional, NP formulations of GSH, LS, and their respective combinations. The effect was evaluated through various tests, and properties of nanoparticles were confirmed through characterization processes. The NP compositions markedly enhanced renal function, as seen by reduced urine concentrations of albumin and glucose. Furthermore, the serum concentrations of creatinine (SCr), blood urea nitrogen (BUN), and cystatin C were decreased. Tissue concentrations of nitrite, superoxide dismutase (SOD), and malondialdehyde (MDA), as markers of oxidative stress, were enhanced by both conventional and NP formulations. Additionally, they decreased inflammatory markers such as kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), tumor necrosis factor alpha (TNF-α), and interleukin-6 (IL-6). Histological analysis and immunohistochemical testing revealed that the combination therapy, particularly with the nanoforms, significantly decreased caspase 3 cellular immunoexpression, a sign of kidney cellular damage. The findings show that the ARF renal damage is considerably reduced when NPs containing GSH and LS are administered together. The study suggests a promising pharmacological approach for enhancing kidney regeneration and preserving renal function, potentially aiding in new therapeutic interventions for ARF treatment.

Purpose

A multitude of inflammatory cells and chemical mediators initiate a complex cascade that ultimately leads to hepatocyte death and a systemic inflammatory response. This research aimed to investigate the potential effects of sildenafil and neem (Azadirachta indica) extract, in both conventional and nanoparticle (NP) forms, in the treatment of moderate acute liver damage induced by orogastric carbon tetrachloride (CCL₄).

Methods

To induce moderate acute hepatic damage a single oral dosage of CCL₄ (2.5 mL/kg body weight) was provided 24 h before euthanasia. In liver damage-induced CCL₄, sildenafil and neem extract were given in conventional and nanoparticle (PLGA or niosome) forms. To find histological anomalies and hepatic changes, behavioral, biochemical, histopathological, and immunohistochemical methods were used.

Results

The findings indicated that sildenafil and/or neem extract, especially in NP combination, significantly mitigated CCL₄-induced acute moderate liver damage. Indicators of liver function, including aspartate aminotransferase (AST), alkaline phosphatase (ALP), alanine aminotransferase (ALT), albumin, bilirubin and gamma-glutamyl transferase (GGT), shown improvement, particularly with the nanoparticulation of both therapies. Treatment, particularly in NP forms, improved the levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase activity (GPx) in liver tissues. A significant reduction in NF-κB expression in hepatic tissue was shown in treatment groups. Also, medication resulted in lower levels of interleukin-1 beta (IL-1β), tumor necrosis factor alpha (TNF-α), caspase-3, and transforming growth factor-beta (TGF-β) in the liver tissue homogenates. Liver function was more significantly improved by the drug-NP combination.

Conclusions

This study verified the beneficial therapeutic effects of the combination of sildenafil and neem extract, particularly in NP forms, using biochemical, histological, and immunohistochemical analyses in a rat model of liver damage.

    This study examines the development of the rabbit cerebellum from the 10th day postconception to full-term fetal age, with a particular focus on the role of radial glial cells in the differentiation of cerebellar neurons. A total of 35 embryonic samples were meticulously dissected and microscopically analyzed. On embryonic day (ED) 12, cerebellar primordia, consisting of the ventricular neuroepithelium and rhombic lip, were observed. By ED16, significant neuronal cell proliferation and migration in both the radial and tangential directions were noted. On ED 20, lamination processes began, forming the external granular layer (EGL) and Purkinje cell plate (PCP) with the support of radial glial cells. By ED 25, the cerebellar cortex had developed three distinct layers: the EGL, PCP, and the prospective molecular layer (PML), with radial glial cells localized in the PCP. Differentiation continued, and upon ED30, a new cortical layer, the internal granular layer, was evident. Additionally, the gradual replacement of nestin by glial fibrillary acidic protein marked the differentiation of radial glia into Bergmann glia at ED 25 and ED 30. β-III tubulin, a marker of differentiated neurons, was detected in the inner layer of EGL and PCP during these stages. In conclusion, this study highlights the pivotal role of radial glial cells in the layered organization and neuronal differentiation of the developing rabbit cerebellum. The developmental trajectory observed provides valuable insights into cerebellar morphogenesis and supports the relevance of the rabbit model for exploring neurodevelopmental processes.

Unlike mammals, species such as fish and amphibians can regenerate damaged spinal
cords, offering insights into potential therapeutic targets. This study investigates the
structural features of the molly fish spinal cord through light and electron microscopy.
The most notable characteristic was the presence of Mauthner cells (M-cells), which
exhibited large cell bodies and processes, as well as synaptic connections with astrocytes. These astrocytic connections contained synaptic vesicles, suggesting electrical
transmission at the M-cell endings. Astrocytes, which were labeled with glial fibrillary
acidic protein (GFAP), contained cytoplasmic glycogen granules, potentially serving as
an emergency fuel source. Two types of oligodendrocytes were identified: a small,
dark cell and a larger, lighter cell, both of which reacted strongly with oligodendrocyte
transcription factor 2 (Olig2). The dark oligodendrocyte resembled human oligodendrocyte precursors, while the light oligodendrocyte was similar to mature human oligodendrocytes. Additionally, proliferative neurons in the substantia grisea centralis
expressed myostatin, Nrf2, and Sox9. Collectively, these findings suggest that the
molly fish spinal cord has advanced structural features conducive to spinal cord
regeneration and could serve as an excellent model for studying central nervous system regeneration. Further studies on the functional aspects of the molly fish spinal
cord are recommended.
 

Fish ovaries exhibit a remarkable diversity in
shape, size, and organization, reflecting the myriad
reproductive strategies employed by different species.
This review delves into the intricate biology of fish
ovaries, highlighting their structural diversity and the
hormonal regulation that governs ovarian development
and oocyte maturation. Key hormones include pituitary
gonadotropins (GTHs) and maturation-inducing
hormones (MIHs), which initiate oocyte growth and
maturation. GTHs stimulate ovarian production of
estradiol-17β and 17α,20β-DP, which induce oocyte
maturation via MPF formation. Sex steroids like
estrogens and progestogens, synthesized from
cholesterol, play crucial roles. Other hormones,
including growth hormone, prolactin, thyroid hormones,
IGFs, ACTH, and melatonin, influence ovarian activity.
The review also explores the varied reproductive
strategies among fish, including oviparity and viviparity,
and discusses how environmental factors like water
temperature and photoperiod influence ovarian
histology. Understanding the complex interplay between
these factors is essential for advancing fisheries
management, conservation, and aquaculture practices.
Additionally, the evolutionary trajectory of fish ovaries
underscores their adaptation to diverse ecological niches,
contributing to the survival and reproductive success of
fish species. The ovarian stroma provides structural
support and houses various cell types, including
dendritic cells (DCs), endocrine cells, and telocytes,
contributing to follicle growth and hormone production,
essential for reproductive success in fish. Fish ovaries
are a crucial aspect of fish biology, with their structure
and function intricately regulated by hormonal,
environmental, and seasonal factors.
 

The structure of photoreceptors (PR) and the arrangement of neurons in the retina of
red-tail shark were investigated using light and electron microscopy. The PR showed
a mosaic arrangement and included double cones, single cones (SC), and single rods.
Most cones occur as SC. The ratio between the number of cones and rods was
3:1.39 (±0.29). The rods were tall that reached the pigmented epithelium. The outer
plexiform layer (OPL) showed a complex synaptic connection between the horizontal
and photoreceptor terminals that were surrounded by Müller cell processes. Electron
microscopy showed that the OPL possessed both cone pedicles and rod spherules.
Each rod spherule consisted of a single synaptic ribbon within the invaginating terminal endings of the horizontal cell (hc) processes. In contrast, the cone pedicles possessed many synaptic ribbons within their junctional complexes. The inner nuclear
layer consisted of bipolar, amacrine, Müller cells, and hc. Müller cells possessed intermediate filaments and cell processes that can reach the outer limiting membrane and
form connections with each other by desmosomes. The ganglion cells were large multipolar cells with a spherical nucleus and Nissl’ bodies in their cytoplasm. The presence of different types of cones arranged in a mosaic pattern in the retina of this
species favors the spatial resolution of visual objects.
 

The specific arrangement and distribution of photoreceptors in the retina can vary among
different fish species, with each species exhibiting adaptations related to its habitat, behavior, and
visual requirements. Poecilia sphenops, a diurnal fish, was the focus of this study. The retinas of a
total of eighteen Molly fish were investigated utilizing light and electron microscopy. The retina
exhibited a square mosaic pattern of the inner segments of cones. This pattern comprised double
cones positioned along the sides of a square, with two types of single cones situated at the center and
corners of the square arrangement across the entire retina. The corner cones were slightly shorter
than the central ones. Additionally, the outer plexiform layer contained both cone pedicles and rod
spherules. The rod spherule consisted of a single synaptic ribbon arranged in a triad or quadrat
junctional arrangement within the invaginating free ends of the horizontal and bipolar cell processes.
On the other hand, cone pedicles have more than one synaptic ribbon in their junctional complex.
The inner nuclear layer consisted of the amacrine, bipolar, Müller, and horizontal cell bodies. Müller
cell processes, expressing GFAP, extended across all retinal layers, segmenting the deeper retina into
alternating fascicles of optic axons and ganglion cells. The outer and inner plexiform layers showed
many astrocyte cell processes expressing GFAP. In conclusion, the current study is the first record of
the retinal structures of Molly fish. This study illustrated the mosaic arrangement of photoreceptors
and GFAP expression patterns of astrocytes and Müller cells. The presence of three cone types,
coupled with a sufficient number of rods, likely facilitates motion awareness for tasks like finding
food and performing elaborate mating ceremonies
 

Unlike adult mammalian cardiomyocytes, cardiomyocytes in teleosts display high proliferative capacity throughout adulthood. This study aimed to identify the immunohistochemical profiles
of cardiomyocytes and immune cells in the hearts of Molly fish by assessing the immunolabelling
expression of key proteins involved in cell proliferation, differentiation, and tissue protection. The
cardiac anatomy of Molly fish includes the atrium, ventricle, and bulbus arteriosus. The expression of
SOX9, NF-κB, myostatin, and S100 proteins in myocardial cells indicates the proliferative features of
the heart in Molly fish. The bulbus arteriosus is characterized by collagenous chambers and smooth
muscle cells that express Ach and iba1. The atrium of Molly fish serves as a storage unit for rodlet
cells and immune cells. Rodlet cells displayed immunoreactivity to NF-κB, iba1, Olig2, Ach, and
S100 proteins, suggesting their roles in the immune response within the heart. Furthermore, telocytes
(TCs) have emerged as a significant component of the atrium of Molly fish, expressing Ach, CD68,
S100 protein, and iba1. These expressions indicate the involvement of TCs in multiple signaling pathways that contribute to heart architecture. This study delineates the intricate relationship between
cardiomyocytes and innate immune cells in Molly fish.
 

Teleost fish exhibit the most pronounced and widespread adult neurogenesis.
Recently, functional development and the fate of newborn neurons have been
reported in the optic tectum (OT) of fish. To determine the role of neurogenesis in
the OT, this study used histological, immunohistochemical, and electron microscopic
investigations on 18 adult Molly fish specimens (Poecilia sphenops). The OT of the
Molly fish was a bilateral lobed structure located in the dorsal part of the mesencephalon. It exhibited a laminated structure made up of alternating fiber and cellular layers,
which were organized into six main layers. The stratum opticum (SO) was supplied by
optic nerve fibers, in which the neuropil was the main component. Radial bipolar neurons that possessed bundles of microtubules were observed in the stratum fibrosum
et griseum superficiale (SFGS). Furthermore, oligodendrocytes with their processes
wrapped around the nerve fibers could be observed. The stratum album centrale
(SAC) consisted mainly of the axons of the stratum griseum centrale (SGC) and the
large tectal, pyriform, and horizontal neurons. The neuronal cells of the SO and large
tectal cells of the SAC expressed autophagy-related protein-5 (APG5). Interleukin-1β
(IL-1β) was expressed in both neurons and glia cells of SGC. Additionally, inducible
nitric oxide synthase (iNOS) was expressed in the neuropil of the SAC synaptic layer
and granule cells of the stratum periventriculare (SPV). Also, transforming growth factor beta (TGF-β), SRY-box transcription factor 9 (SOX9), and myostatin were clearly
expressed in the proliferative neurons. In all strata, S100 protein and Oligodendrocyte
Lineage Transcription Factor 2 (Olig2) were expressed by microglia, oligodendrocytes,
and astrocytes. In conclusion, it was possible to identify different varieties of neurons
in the optic tectum, each with a distinct role. The existence of astrocytes, proliferative
neurons, and stem cells highlights the regenerative capacity of OT
 

The bulbus arteriosus of goldfish, Carassius auratus, possesses unique structural features.
The wall of the bulbus arteriosus is exceptionally thick, with an inner surface characterized by
longitudinally arranged finger-like ridges, resulting in an uneven luminal appearance. These ridges
are covered by endocardium and encased in an amorphous extracellular matrix. The inner surface
of the bulbus arteriosus also contains rodlet cells at different developmental stages, often clustered
beneath the endothelium lining the bulbar lumen. Ruptured rodlet cells release their contents via
a holocrine secretion process. The high abundance of rodlet cells in the bulbus arteriosus suggests
that this is the site of origin for these cells. Within the middle layer of the bulbus arteriosus, smooth
muscle cells, branched telocytes (TCs), and collagen bundles coexist. TCs and their telopodes form
complex connections within a dense collagen matrix, extending to rodlet cells and macrophages.
Moreover, the endothelium makes direct contact with telopodes. The endocardial cells within the
bulbus arteriosus display irregular, stellate shapes and numerous cell processes that establish direct
contact with TCs. TEM reveals that they contain moderately dense bodies and membrane-bound
vacuoles, suggesting a secretory activity. TCs exhibit robust secretory activity, evident from their
telopodes containing numerous secretory vesicles. Furthermore, TCs release excretory vesicles
containing bioactive molecules into the extracellular matrix, which strengthens evidence for telocytes
as promising candidates for cellular therapies and regeneration in various heart pathologies.