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ABSTRACT Purpose: Blackberries are rich in polyphenols and are a human health food continuously consumed to improve health and reduce diseases caused by aging. Herein, we evaluated the effects of daily blackberry administration before and after transient cerebral ischemia in gerbils. Methods: Blackberry extract (BBE) was orally administered twice a day for two weeks to protect against ischemic events during continuous administration. On the seventh day after administration, the bilateral common carotid arteries were transiently occluded for 5 min. To verify its therapeutic effect, BBE was administered after ischemia using a similar protocol without pre-administration. In both experiments, the number of viable neurons in the CA1 region of the hippocampus was assessed seven days after ischemic treatment. Results: The number of neurons in the group treated with BBE before ischemia was higher than that in the group treated with distilled water (p = 0.0601), and similar to that in the control group. In the BBE administration experiments after ischemia, the number of neurons was significantly reduced compared to that in the control group (p < 0.0001). Conclusions: Continuous BBE intake is expected to prevent or ameliorate ischemic events such as transient cerebral ischemia.

The enamel knot (EK), located at the center of cap stage tooth germs, is a transitory cluster of nondividing epithelial cells. The EK acts as a signaling center that provides positional information for tooth morphogenesis and regulates the growth of tooth cusps. To identify species-specific cuspal patterns, this study analyzed the cellular mechanisms in the EK that were related to bone morphogenetic protein (Bmp), which plays a crucial role in cell proliferation and apoptosis. To understand the cellular mechanisms in the EK, the differences between 2 species showing different cuspal patterning, mouse (pointy bunodont cusp) and gerbil (flat lophodont cusp), were analyzed with quantitative reverse transcriptase polymerase chain reaction and immunofluorescent staining. Based on these, we performed protein-soaked bead implantation on tooth germs of the 2 different EK regions and compared the cellular behavior in the EKs of the 2 species. Many genes related with cell cycle, cell apoptosis, and cell proliferation were involved in BMP signaling in the EK during tooth development. A comparison of the cell proliferation and apoptosis associated with Bmp revealed distinctive patterns of the cellular mechanisms. Our findings indicate that the cellular mechanisms, such as cell proliferation and apoptosis, in the EK are related to Bmp4 and play an important role in tooth morphogenesis. [ABSTRACT FROM AUTHOR]

The Guenfouda cave, located in eastern Morocco, has yielded an abundant macro- and microvertebrate fauna associated with a rich lithic industry attributed to several cultures (Middle Stone Age, Later Stone Age and Neolithic). Among the microfauna, on the basis of new morphological and biometric data of the upper and lower first molars, we identified two gerbillines of the genus Gerbillus collected from the upper levels of an Holocene age. Gerbillus henleyi is here identified for the first time in the fossil record of North Africa, while G. campestris has been cited previously at this site and in many other Pleistocene and Holocene sites in the Maghreb. The taphonomic study concluded that a medium-sized nocturnal predator (possibly Tyto alba) was likely to be the source of the accumulation of small mammals in the filling of the Guenfouda cave. The palaeoecological reconstruction based on the whole faunal spectrum indicates a semi-open steppic landscape, with patches of more wooded areas and water ponds or streams, which is also characteristic for this region at present. [ABSTRACT FROM AUTHOR]

To enrich the mitogenomic database of Gerbillinae (Rodentia: Muridae), mitogenomes of three gerbils from different genera, Meriones tamariscinus (16,393 bp), Brachiones przewalskii (16,357 bp), and Rhombomys opimus (16,352 bp), were elaborated and compared with those of other gerbils in the present study. The three gerbil mitogenomes consisted of 2 ribosomal RNA genes, 13 protein-coding genes (PCGs), 22 transfer RNA genes, and one control region. Here, gerbil mitogenomes have shown unique characteristics in terms of base composition, codon usage, non-coding region, and the replication origin of the light strand. There was no significant correlation between the nucleotide percentage of G + C and the phylogenetic status in gerbils, and between the GC content of PCGs and the leucine count. Phylogenetic relationships of the subfamily Gerbillinae were reconstructed by 7 gerbils that represented four genera based on concatenated mitochondrial DNA data using both Bayesian Inference and Maximum Likelihood. The phylogenetic analysis indicated that M. tamariscinus was phylogenetically distant from the genus Meriones, but has a close relationship with R. opimus. B. przewalskii was closely related to the genus Meriones rather than that of R. opimus. [ABSTRACT FROM AUTHOR]

Muscles are crucial for balance and walking, activities which depend specifically on the lower extremity muscles. Therefore, the evaluation of stroke induced atrophy and paralysis is essential; however, determining the extent of damage in the days after its occurrence remains challenging. In this study, we evaluated ischemic stroke-induced soleus muscle damage in gerbils using synchrotron radiation X-ray micro-computed tomography (SR-µCT), comparing a control group (n = 3), animals 7 days after stroke (7 d, n = 3), and animals 14 days after stroke (14 d, n = 3). The left muscle was paralyzed, whereas the right muscle was not. Subsequently, we quantified the assessment by segmenting the soleus muscle based on the extracellular space/matrix and fiber region to determine the degree of damage. The muscle fiber-to-extracellular space/matrix ratio were significantly damaged due to paralysis on the left side (control vs. 14 d, P = 0.040). Muscle area was significantly different at 14 d between the left and right sides (P = 0.010). Additionally, the left local fascicle surface area, thickness, global pennation angle, and local fascicle angle were significantly different between the control and 14 d groups (P = 0.002, P = 0.007, P = 0.005, and P = 0.014 respectively). These findings underscore the potential of post-stroke animal studies in improving rehabilitation treatment for the central nervous system by assessing the degree of muscle recovery., (© 2024. The Author(s).)

Exposure to pesticides, individually or in a mixture, in drinking water is one of the main sources of human contamination, which causes adverse effects on the reproductive system. Our study aimed to investigate, the effects of a 90-day exposure to low concentrations of glyphosate (GLY), atrazine (ATZ), and 2,4-dichlorophenoxyacetic acid (2,4-D), in commercial formulations, on morphological, molecular, and hormonal parameters of the ventral prostate of gerbils (Meriones unguiculatus). The animals were exposed via drinking water to individual concentrations of GLY: 700 μg/L, ATZ: 3 μg/L, and 2,4-D: 70 μg/L, as well as to their mixture (MIX). Our findings showed an increase in prostatic complex relative weight in ATZ-exposed animals. Stereological and morphometric techniques indicated an increase in the percentage and thickness of muscular stroma, following an increase in the amount of collagen and reticular fibers in the MIX group. Histopathological analysis showed a decrease in the incidence of epithelial atrophy, subepithelial inflammation, and microacini in the MIX. On the other hand, ATZ-exposed animals showed an increase in hyperplasia and total prostatic intraepithelial neoplasia (PIN). The expression of caspase-3 decreased and estrogen receptor alpha (ERα) increased in the 2,4-D and MIX. Western blotting showed an increase in estrogen receptor beta (ERβ) expression in MIX-exposed animals. Testosterone levels decreased in animals from the GLY, ATZ and 2,4-D groups. Our findings provide evidence that individual or combined exposure to herbicides causes hormonal imbalance and morphological alterations, besides favoring the incidence of proliferative lesions in the prostate, predisposing the gland to more severe injuries., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Hepatitis E virus (HEV) is one of the major pathogens causing acute viral hepatitis worldwide, which usually causes acute self-limited diseases in general individuals. However, it can lead to high mortality and adverse pregnancy outcomes in pregnant women. Due to the lack of effective and stable cell culture models for HEV, the establishment of suitable animal models for HEV infection during pregnancy is necessary. An electronic search of the relevant database was conducted to identify eligible articles. Main animal models for the study of HEV infection during pregnancy include rabbits, swine, nonhuman primates and Mongolian gerbils. These animal models have been used to study the prevention, treatment and possible mechanisms of HEV infection during pregnancy. Studies using these animal models have investigated the potential pathogenesis of HEV infection during pregnancy. It has been found that immune mechanism (changes in the CD4/CD8 ratio and cytokines), hormonal changes (increase in pregnancy-related hormones) and viral factors (different genotypes and genome structures) can lead to HEV-related adverse pregnancy outcomes in animal models. In this review, we aimed to comprehensively present the characteristics of different animal models and the pathogenesis of HEV-related adverse pregnancy outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financialinterests or personal relationships that could have appeared to influencethe work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: Develop a novel and highly efficient framework that decodes Inferior Colliculus (IC) neural activities for phoneme recognition., Methods: We propose using Hyperdimensional Computing (HDC) to support an efficient phoneme recognition algorithm, in contrast to widely applied Deep Neural Networks (DNN). The high-dimensional representation and operations in HDC are rooted in human brain functionalities and naturally parallelizable, showing the potential for efficient neural activity analysis. Our proposed method includes a spatial and temporal-aware HDC encoder that effectively captures global and local patterns. As part of our framework, we deploy the lightweight HDC-based algorithm on a highly customizable and flexible hardware platform, i.e., Field Programmable Gate Arrays (FPGA), for optimal algorithm speedup. To evaluate our method, we record IC neural activities on gerbils while playing the sound of different phonemes., Results: We compare our proposed method with multiple baseline machine learning algorithms in recognition quality and learning efficiency, across different hardware platforms. The results show that our method generally achieves better classification quality than the best-performing baseline. Compared to the Deep Residual Neural Network (i.e., ResNet), our method shows a speedup up to 74×, 67×, 210× on CPU, GPU, and FPGA respectively. We achieve up to 15% (10%) higher accuracy in consonant (vowel) classification than ResNet., Conclusion: By leveraging brain-inspired HDC for IC neural activity encoding and phoneme classification, we achieve orders of magnitude runtime speedup while improving accuracy in various challenging task settings., Significance: Decoding IC neural activities is an important step to enhance understanding about human auditory system. However, these responses from the central auditory system are noisy and contain high variance, demanding large-scale datasets and iterative model fine-tuning. The proposed HDC-based framework is more scalable and viable for future real-world deployment thanks to its fast training and overall better quality.

Hepatitis E virus (HEV) is a foodborne zoonotic pathogen that is supposed to be one of the most common causes of acute viral hepatitis. However, HEV infection has been recently associated with a wide spectrum of extrahepatic manifestations, particularly neurological disorders. Previous studies have shown that HEV is able to cross the blood-brain barrier (BBB) and induce inflammatory response of the central nervous system. However, the pathogenesis of HEV-induced neuroinflammation and tissue injury of the central nervous system have yet to be fully elucidated. In this study, activation of NLRP3 inflammasome following HEV infection were investigated. In a gerbil model infected by HEV, brain histopathological changes including gliosis, neuronophagia and neuron injury were observed and expression of NLRP3, caspase-1, IL-1β and IL-18 were elevated. Brain microvascular endothelial cells (BMECs) are key components of the BBB that protects the brain from various challenges. Following HEV infection, virus-like particles range from 30 to 40 nm in diameter were observed in human BMECs (hBMECs). Enhanced expression levels of NLRP3 and subsequent ASC, caspase-1, IL-1β and IL-18 were detected in infected cells. Treatment with MCC950 alleviated HEV infection induced activation of NLRP3 inflammasome, mitochondrial damage and VE-cadherin degradation. The findings provide new insights into HEV-associated neuroinflammation. Moreover, targeting NLRP3 inflammasome signalling is a promising therapeutic in HEV-induced neurological disorder., (© 2024 John Wiley & Sons Ltd.)

It is established that neurogenesis of dentate gyrus is increased after ischemic insult, although the regulatory mechanisms have not yet been elucidated. In this study, we focused on Ezh2 which suppresses gene expression through catalyzing trimethylation of lysine 27 of histone 3. Male gerbils were injected with adeno-associated virus (AAV) carrying shRNA targeting to Ezh2 into right dentate gyrus 2 weeks prior to forebrain ischemia. One week after ischemia, animals were injected with thymidine analogue to label proliferating cells. Three weeks after ischemia, animals were killed for histological analysis. AAV-mediated knockdown of Ezh2 significantly decreased the ischemia-induced increment of proliferating cells, and the proliferated cells after ischemia showed significantly longer migration from subgranular zone (SGZ), compared to the control group. Furthermore, the number of neural stem cells in SGZ significantly decreased after ischemia with Ezh2 knockdown group. Of note, Ezh2 knockdown did not affect the number of proliferating cells or the migration from SGZ in the non-ischemic condition. Our data showed that, specifically after ischemia, Ezh2 knockdown shifted the balance between self-renewal and differentiation toward differentiation in adult dentate gyrus., (© 2024. The Author(s).)

Temporal niche partitioning is a crucial strategy for sympatric species to avoid predation and competition for habitat space and food resources. This study investigated the effect of the gut microbiota on the metabolic rhythms of two sympatric gerbil species (Meriones unguiculatus and Meriones meridianus) to test the hypothesis that the oscillatory patterns of microbiota may not fully mirror those of the host's metabolism. Experiment 1 compared the circadian metabolic and gut microbiota rhythms of M. unguiculatus (n = 12) and M. meridianus (n = 12) and measured the subjects' body temperatures and environmental temperature preferences. In Experiment 2.1, six M. meridianus gerbils were treated with antibiotics, and in Experiment 2.2, 21 M. unguiculatus gerbils (seven per treatment) were randomly gavaged with saline or a gut microbiota suspension from either M. unguiculatus or M. meridianus; their metabolic rhythms were subsequently measured. The results showed that the two gerbils had different metabolic phenotypes that determined activity heterogeneity and contributed to their coexistence. The relative abundances of Bacteroidetes, Actinobacteria, and Cyanobacteria in M. meridianus varied rhythmically in parallel with the daily metabolic rate, which was significantly higher at night than during the day. The rhythm of the metabolic rate was not noticeable in M. unguiculatus. However, in M.unguiculatus, the relative abundances of Firmicutes, Bacteroidetes, Proteobacteria, and Verrucomicrobia were significantly higher during the day than at night, while Cyanobacteria exhibited the opposite pattern. Antibiotic treatment significantly weakened the metabolic rhythms of M. meridianus, and the circadian rhythms slowly recovered after stopping antibiotic gavage. However, after transplanting M. meridianus' gut microbiota into M. unguiculatus, the metabolic rate of M. unguiculatus was not significantly different from that of the control groups. Our hypothesis was partly supported: the microbiota was only partially involved in regulating the metabolic rhythms of gerbils, and other factors could compensate for the effect of the gut microbiota on host metabolic rhythms. This finding underscores the complexity of host-microbiota interactions and highlights the need for further exploration into the multifaceted mechanisms governing host metabolic regulation., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:, (Copyright © 2024 Elsevier Inc. All rights reserved.)

Fleas, along with one of their host species, Meriones unguiculatus, possess the capability to act as vectors in the transmission of plague. Parasitism by fleas may markedly influence the physiology and immune system of their hosts. Gut microbiota plays an important role in the growth and development of rodents. However, few studies have explored the impacts of ectoparasitic flea on the gut microbiome of rodents. This study investigated the immunological responses and changes in the gut microbial diversity and composition in both wild and laboratory rodents infested with fleas and laboratory rodents infested with Ctenocephalides felis. We measured immune reactions post-infestation by enzyme-linked immunosorbent assay (ELISA) and explored the effects of ectoparasitic infestation on the diversity and composition of the rodent gut microbiota in microbiome studies by 16S rRNA gene sequencing techniques. After flea infestation, results from 16S rRNA gene sequencing techniques indicated a significant increase in alpha diversity, affecting the composition of the gut microbiota. At the genus level, the abundance of the harmful bacterium Desulfovibrio increased. Beta diversity analyses showed significant differences between the gut microbiota of the experimental and control groups. ELISA results revealed significantly elevated levels of IgG in parasitized mice, while the differences in IgA levels were not significant. Flea infections affect the composition and diversity of the gut microbiota in the M. unguiculatu, and it has been found that the biomarker Desulfovibrio increases following flea infection in these rodents. Our results indicate that the gut microbiota can regulate the stability of the rodent-flea system. These findings may provide a foundation for exploring preventive measures against plague and aid in developing more effective treatments for the infection., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Obesity is a predisposing risk factor for type 2 diabetes mellitus (T2DM). Actually, not only obese/overweight but also nonobese/lean individuals may be prone to T2DM. This study is aimed at identifying the contribution of adipose tissue to the development of nonobese diabetes (NOD) and obese diabetes (OD). Methods: Serum samples from the nonobese nondiabetes (NOND, n = 47, age = 46.8 ± 8.4, BMI ≤ 23.9 kg/m 2 ) controls, NOD ( n = 48, age = 50.7 ± 6.5, BMI ≤ 23.9 kg/m 2 ) and OD (n = 65, age = 49.8 ± 10.2, BMI ≥ 28 kg/m 2 ) patients were utilized to measure the expression of metabolic indicators, adipocytokines, inflammatory factors. Different adipose depots from offspring with corresponding blood glucose and obesity levels of a spontaneously diabetic gerbil line with various degrees of diabetic penetrance and body weights were examined for adipocytokines and inflammation factors detected by ELISA and western blot. Adipose tissue volume and fat cell size of the gerbils were evaluated by magnetic resonance imaging and immunohistochemistry, respectively. Results: The study yielded four key findings. Firstly, in comparison to the NOD group, the OD group exhibited more severe insulin resistance (IR) and metabolic dysfunction in both patients and gerbils, attributed to higher visceral adipose tissue mass and larger fat cell sizes. Secondly, in gerbils, gonadal fat deposition was linked to obesity development, whereas kidney fat deposition correlated with obesity and diabetes occurrence. Thirdly, in both patients and gerbils, the interplay between adiponectin and leptin levels in serum may significantly influence the development of obesity and diabetes. Lastly, heightened expression of MCP3 in gerbils' kidney adipose tissue may serve as a pivotal factor in initiating obesity-associated diabetes. Conclusions: Our study, which may be considered a pilot investigation, suggests that the interaction of adipocytokines and inflammation factors in different adipose depots could play diverse roles in the development of diabetes or obesity., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Hongjuan Fang et al.)

The enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB) plays an essential role in glycolysis and in the antioxidant pathway associated with glutathione. Therefore, we investigated the effects of PFKFB3 on oxidative and ischemic damage. We synthesized a fusion protein of transactivator of transcription (Tat)-PFKFB3 to facilitate its passage into the intracellular space and examine its effects against oxidative stress induced by hydrogen peroxide (H 2 O 2 ) treatment and ischemic damage caused by occlusion of the common carotid arteries for 5 min in gerbils. The Tat-PFKFB3 protein was efficiently delivered into HT22 cells in a concentration- and time-dependent manner, with higher levels observed 18 h after treatment. Furthermore, treatment with 6 µM Tat-PFKFB3 demonstrated intracellular delivery into HT22 cells, as analyzed through immunocytochemical staining. Moreover, it significantly ameliorated the reduction of cell viability induced by 200 µM H 2 O 2 treatment. Tat-PFKFB3 treatment also alleviated H 2 O 2 -induced DNA fragmentation and reactive oxygen species formation in HT22 cells. In gerbils, the intraperitoneal administration of 2 mg/kg Tat-PFKFB3 efficiently delivered the substance to all hippocampal areas, including the hippocampal CA1 region. This administration significantly mitigated ischemia-induced hyperlocomotion, long-term memory deficits, and ischemic neuronal death in the hippocampal CA1 region after ischemia. Additionally, treatment with 2 mg/kg Tat-PFKFB3 significantly ameliorated the translocation of Cdk5 from the cytosol to the nucleus in the hippocampal CA1 region 24 h after ischemia, but not in other regions. The treatment also significantly reduced reactive oxygen species formation in the CA1 region. These findings suggest that Tat-PFKFB3 reduces neuronal damage in the hippocampal CA1 region after ischemia through the reduction of Cdk5 signaling and reactive oxygen species formation. Therefore, Tat-PFKFB3 may have potential applications in reducing ischemic damage., (© 2024. The Author(s).)

Most scientists agree that subjective tinnitus is the pathological result of an interaction of damage to the peripheral auditory system and central neuroplastic adaptations. Here we investigate such tinnitus related adaptations in the primary auditory cortex (AC) 7 and 13 days after noise trauma induction of tinnitus by quantifying the density of the extracellular matrix (ECM) in the AC of Mongolian gerbils (Meriones unguiculatus). The ECM density has been shown to be relevant for neuroplastic processes and synaptic stability within the cortex. We utilized a mild monaural acoustic noise trauma in overall 22 gerbils to induce tinnitus and a sham exposure in 16 control (C) animals. Tinnitus was assessed by a behavioral response paradigm. Animals were separated for a presence (T) or absence (NT) of a tinnitus percept by a behavioral task. The ECM density 7 and 13 days after trauma was quantified using immunofluorescence luminance of Wisteria floribunda lectin-fluoresceine-5-isothiocyanate (WFA-FITC) on histological slices of the primary AC, relative to the non-auditory brainstem as a reference area. At both timepoints, we found that the WFA-FITC luminance of the AC of NT animals was not significantly different from that of C animals. However, we found a significant increase of luminance in T animals' ACs compared to NT or C animals' cortices. This effect was found exclusively on the AC side contralateral to the trauma ear. These results point to a hemisphere specific process of stabilization of synaptic connections in primary AC, which may be involved in the chronic manifestation of tinnitus., (© 2024. The Author(s).)

The perforation characteristics and fracture-related mechanical properties of the tympanic membrane (TM) greatly affect surgical procedures like myringotomy and tympanostomy performed on the middle ear. We analyzed the most important features of the gerbil TM perforation using an experimental approach that was based on force measurement during a 2-cycle needle insertion/extraction process. Fracture energy, friction energy, strain energy, and hysteresis loss were taken into consideration for the analysis of the different stages of needle insertion and extraction. The results demonstrated that (1) although the TM shows viscoelastic behavior, the contribution of hysteresis loss was negligible compared to other irreversible dissipated energy components (i.e., fracture energy and friction energy). (2) The TM puncture force did not substantially change during the first hours after animal death, but interestingly, it increased after 1 week due to the drying effects of soft tissue. (3) The needle geometry affected the crack length and the most important features of the force-displacement plot for the needle insertion process (puncture force, puncture displacement, and jump-in force) increased with increasing needle diameter, whereas the insertion velocity only changed the puncture and jump-in forces (both increased with increasing insertion velocity) and did not have a noticeable effect on the puncture displacement. (4) The fracture toughness of the gerbil TM was almost independent of the needle geometry and was found to be around 0.33 ± 0.10 kJ/m 2 ., (© 2024. The Author(s) under exclusive licence to Association for Research in Otolaryngology.)

The tympanic membrane (TM) is one of the most common routes to access the middle ear and inner ear for the treatment of hearing and balance pathologies. Since the TM is a soft thin biological tissue with small dimensions, using needles seems to be among the most practical interventional approaches. In this study, we proposed a finite-element (FE) analysis of needle-TM interactions that combines a 3D model of the TM and other main middle-ear structures in gerbil, and a 2D model of needle insertion into the TM based on the cohesive zone method (CZM). The TM was modelled using a 1 st -order Ogden hyperelastic material and its properties were obtained by fitting to the experimental force-displacement plots of large deformation in the TM under needle indentation. The cohesive parameters were also acquired by calibrating the puncture force against the experimental data of needle insertion into the TM. These FE models were then used to obtain the deformation behaviour of the TM and other middle-ear structures due to the insertion force applied at different locations on the TM. Moreover, we investigated the effect of the TM thickness, the geometry of the needle (i.e., diameter and tip angle), and needle material on the insertion of needles into the TM. We also studied the penetration success of deformable needles., (Copyright © 2024. Published by Elsevier B.V.)

Current research using animal models to investigate retinal cell biology and model retinal degenerative diseases largely utilize small mammals that are nocturnal and lack the ability to restore lost vision. In contrast, the Mongolian gerbil (Meriones) is a diurnal rodent with good photopic vision, and the spiny mouse (Acomys) is a small desert-dwelling rodent with remarkable regenerative capabilities. The goal of this study was to identify antibodies that detect retinal cell classes in Meriones and Acomys, and to describe the retinal anatomy of these two species in comparison to outbred laboratory mice (Mus musculus). Immunohistochemistry was performed on retinal sections with antibodies for various retinal cell types. Sections were imaged by light, fluorescence, and confocal microscopy. Cell density, morphology, and placement were compared between species qualitatively and quantitatively. Our analyses revealed a classic assembly of retinal cells in Meriones and Acomys, with a few deviations compared to Mus. Meriones displayed the highest density of cones and Acomys the lowest. A higher density of bipolar cell bodies in the proximal portion of the inner nuclear layer was observed in both Acomys and Meriones compared to Mus, and both species exhibited an increase in amacrine cell density compared to Mus. Our results provide a foundation for future research into the visual system adaptations of these interesting species., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The study aimed to investigate the repercussions of androgen modulation on the adrenal cortex of male gerbils, focusing on the morphophysiology, proliferation, and cell death, as well as the expression of hormone receptors and steroidogenic enzymes. Mongolian gerbils (Meriones unguiculatus) were divided into three experimental groups: Control (C), Testosterone (T), animals received injections of testosterone cypionate and Castrated (Ct), animals underwent orchiectomy. The results showed that castration increased the zona fasciculata and promoted cell hypertrophy in all zones. Testosterone supplementation increased cell proliferation and cell death. Androgen modulation promoted an increase in AR, Erα, and ERβ. Castration promoted an increase in the CYP19, while decreasing 17βHSD enzymes. Testosterone supplementation, on the other hand, reduced CYP17 and increased CYP19 and 3βHSD enzymes. By analyzing the effects of androgen supplementation and deprivation, it can be concluded that testosterone is responsible for tissue remodeling in the cortex, regulating the rate of cell proliferation and death, as well as cell hypertrophy. Testosterone also modulate steroid hormone receptors and steroidogenic enzymes, consequently affecting the regulation, hormone synthesis and homeostasis of this endocrine gland., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Although pair bonding has been studied for several decades, only somewhat recently have researchers began studying the neural consequences of separation from a pair bond partner. Here we examined the impact of partner separation on the socially monogamous Mongolian gerbil. Using a within-subjects design, we assessed nonsocial, nonreproductive, and reproductive behavior in male gerbils pre- and post- either 4 weeks of cohabitation with or separation from a pair bond partner. We then conducted an immediate early gene study to examine the influence of partner separation on hypothalamic oxytocin and vasopressin neural responses to interactions with a novel, opposite-sex conspecific., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: Blackberries are rich in polyphenols and are a human health food continuously consumed to improve health and reduce diseases caused by aging. Herein, we evaluated the effects of daily blackberry administration before and after transient cerebral ischemia in gerbils., Methods: Blackberry extract (BBE) was orally administered twice a day for two weeks to protect against ischemic events during continuous administration. On the seventh day after administration, the bilateral common carotid arteries were transiently occluded for 5 min. To verify its therapeutic effect, BBE was administered after ischemia using a similar protocol without pre-administration. In both experiments, the number of viable neurons in the CA1 region of the hippocampus was assessed seven days after ischemic treatment., Results: The number of neurons in the group treated with BBE before ischemia was higher than that in the group treated with distilled water (p = 0.0601), and similar to that in the control group. In the BBE administration experiments after ischemia, the number of neurons was significantly reduced compared to that in the control group (p < 0.0001)., Conclusions: Continuous BBE intake is expected to prevent or ameliorate ischemic events such as transient cerebral ischemia.

Background & Aims: Hepatitis E virus (HEV), primarily genotype 1 (HEV-1), causes approximately 20.1 million infections, 44,000 deaths, and 3000 stillbirths annually. Current evidence indicates that HEV-1 is only transmitted in humans. Here, we evaluated whether Mongolian gerbils can serve as animal models for HEV-1 infection., Methods: Mongolian gerbils were used for HEV-1 and hepatitis E virus genotype 3 infection experiments. HEV infection parameters, including detection of HEV RNA and HEV antigen, liver function assessment, and histopathology, were evaluated., Results: We adapted a clinical isolate of HEV-1 for Mongolian gerbils by serial passaging in feces of aged male gerbils. The gerbil-adapted strain obtained at passage 3 induced a robust, acute HEV infection, characterized by stable fecal virus shedding, elevated liver enzymes, histopathologic changes in the liver, and seroconversion to anti-HEV. An infectious complementary DNA clone of the adapted virus was generated. HEV-1-infected pregnant gerbils showed a high rate of maternal mortality and vertical transmission. HEV RNA or antigens were detected in the liver, kidney, intestine, placenta, testis, and fetus liver. Liver and placental transcriptomic analyses indicated activation of host immunity. Tacrolimus prolonged HEV-1 infection, whereas ribavirin cleared infection. The protective efficacy of a licensed HEV vaccine was validated using this model., Conclusions: HEV-1 efficiently infected Mongolian gerbils. This HEV-1 infection model will be valuable for investigating hepatitis E immunopathogenesis and evaluating vaccines and antivirals against HEV., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

The female prostate, also known as Skene's gland, is present in both humans and rodents. Prenatal exposure to ethinylestradiol (EE2), a synthetic estrogen found in oral contraceptives, induces pormotes neoplasic prostate lesions in gerbils ( Meriones unguiculatus ). Conversely, pequi oil (Pe), extracted from the Brazilian Cerrado fruit, has antioxidant, anti-inflammatory, and anticancer properties, mitigates risks associated with chronic diseases related to lifestyle and aging. This study evaluates the impact of prenatal exposure to Pe (300 mg/kg) on senile gerbil offspring's male and female prostates under normal conditions and EE2 exposure (15 μg/kg/day). Histological and morphometric analyses revealed that Pe reduced male body weight and prostate epithelial height, along with a thinner muscle layer. In females, EE2 exposure reduced prostatic weight, while Pe exposure lowered epithelial height and the relative stromal compartment volume, increasing the muscle layer. Pequi oil holds potential in mitigating alterations induced by exposure to the endocrine disruptor EE2.

Selection of the appropriate species and strain of laboratory animals are among the scientist's major concerns. Tarabul's gerbil (Gerbillus tarabuli) is a small, seasonally breeding, desert rodent native to Africa. Despite its unique biological features, which make it an ideal model candidate for biomedical research, only a few reports have used it in research. Hence, the present review aims to provide more data about this species, covering all aspects of its biology, such as taxonomy, morphology, anatomy, ecology, wildlife biology, molecular biology, physiology, neurobiology, genetics, reproduction, development, evolutionary biology, and conservation biology, and covers current progress in exploration of G. tarabuli, discussing its valuable characteristics, which are widely useful for research in various fields. This review paper is destined for biologists, scientists, mammologists, zoologists, academics, and students. [ABSTRACT FROM AUTHOR]

Sensorineural hearing loss (SNHL) constitutes a major global health challenge, affecting millions of individuals and substantially impairing social integration and quality of life. The complexity of the auditory system and the multifaceted nature of SNHL necessitate advanced methodologies to understand its etiology, progression, and potential therapeutic interventions. This review provides a comprehensive overview of the current animal models used in SNHL research, focusing on their selection based on specific characteristics and their contributions to elucidating pathophysiological mechanisms and evaluating novel treatment strategies. It discusses the most commonly used rodent models in hearing research, including mice, rats, guinea pigs, Mongolian gerbils, and chinchillas. Through a comparative analysis, this review underscores the importance of selecting models that align with specific research objectives in SNHL studies, discussing the advantages and limitations of each model. By advocating for a multidisciplinary approach that leverages the strengths of various animal models with technological advancements, this review aims to facilitate significant advancements in the prevention, diagnosis, and treatment of sensorineural hearing loss., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Haemonchus contortus is a highly pathogenic blood-feeding parasite affecting sheep and goats, leading to significant economic losses. With increasing resistance to conventional anthelmintics, exploring plant-based alternatives is crucial. In vitro, studies suggest that peruvin and hentriacontane/1-nonacosanol, isolated from Artemisia cina (Asteraceae), may synergistically control Haemonchus contortus. However, their in vivo efficacy and safety are unestablished. This study evaluated these compounds' anthelmintic activity and health effects and their synergistic mixture in Meriones unguiculatus (gerbils). The compounds were isolated using open-column chromatography and identified by spectroscopic techniques. Gerbils were artificially infected with H. contortus following dexamethasone treatment to enhance infection. Anthelmintic activity was assessed by larval reduction in the stomach, blood biochemical parameters using a blood chemistry analyzer, and the anatomopathological changes in kidney and liver tissues. Peruvin (0.4 mg/kg) and hentriacontane/1-nonacosanol (2.60 mg/kg) achieved larvicidal reductions of 84.86 % and 74.05 %, respectively, while their synergistic mixture (0.08/0.0017 mg/kg) resulted in a 100 % reduction. Histopathological analysis revealed minor inflammation and albuminous degeneration, primarily affecting the liver. The peruvin-treated group showed notable kidney damage, while hepatic alterations were similar across both compounds. Although effective, further research is needed to optimize dosing and ensure safety., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Rosa Isabel Higuera-Piedrahita reports financial support was provided by Support Program for Research and Technological Innovation Projects (PAPIIT-UNAM) TA200324. Luis David Arango-De la Pava reports financial support was provided by National Autonomous University of Mexico Directorate General of Academic Staff Affairs. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Aging causes changes in liver morphophysiology, altering hepatocyte morphology and organ function. Due to its antioxidant and anti-inflammatory properties, coconut oil has been used as a therapeutic agent in diets, in an attempt to attenuate alterations in the liver naturally caused by aging. Herein, we evaluated the effects of coconut oil consumption during aging on Mongolian gerbil liver morphophysiology. The animals were divided into three experimental groups: the gerbils in the Adult Control Group (AC) were euthanized at 3 months of age, the gerbils in the Old Control Group (OC) at 15 months of age, and the gerbils in the Coconut Oil Group (CO) received 0.1 ml/day of coconut oil for 12 months and were euthanized at 15 months of age. Prolonged consumption of coconut oil during aging prevented the animals and the liver from gaining mass. However, the other results showed that coconut oil intensified the morphophysiological alterations of aging, promoting an increase in the hepatocyte cytoplasm and nuclei. In addition, an increase in blood vessels, reticular fibers, lipid droplets, and lipofuscin granules were observed in the CO group. Finally, the results also demonstrated that coconut oil promotes an increase in lipid peroxidation, indicated by an increase in MDA levels. We therefore conclude that coconut oil has the potential to intensify the morphophysiological alterations that occur in the liver during aging., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

17α-Ethinylestradiol is an endocrine-disrupting chemical that make up most contraceptive pills and can be found in the environment. Exposure to ethinylestradiol in different development periods may promote changes in morphophysiological parameters of reproductive and endocrine organs. Considering that the effects of low doses (15 µg/kg/day) of ethinylestradiol in ovaries from 12-month-old female gerbils (Meriones unguiculatus) were investigated. Four experimental groups used were control (without treatment), EE/PRE (treated from the 18th to the 22nd gestational day), EE/PUB (treated from the 42nd to the 49th day of life), and EE/PRE-PUB (treated in the both periods). The animals were euthanized at 12 months. Testosterone and 17β-estradiol levels were measured. The ovaries were stained with Hematoxylin and Eosin, Periodic Acid Schiff, and Gomori's Trichome. The follicles, corpus luteum, interstitial gland, lipofuscin, ovarian epithelium, and tunica albuginea were analyzed. Estradiol was higher in EE/PRE and EE/PUB groups, while testosterone was higher only in EE/PUB group. The main changes in follicle count occurred in EE/PUB and EE/PRE-PUB groups, with higher primordial follicle count and lower maturation of follicles. The corpus luteum was more evident in EE/PRE group. No differences were found in atretic follicles count. A higher area occupied by interstitial gland cells and lipofuscin deposit in these cells was noted in EE/PUB and EE/PRE-PUB groups. Higher epithelium height and thicker tunic albuginea were showed in treated groups. These results suggest that exposure to doses of EE2 in prenatal and pubertal periods of the development leads to morphological changes in senile ovaries. [ABSTRACT FROM AUTHOR]

Previous studies have suggested a role for selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine (Prozac ® ) in the treatment of dizziness and inner ear vestibular dysfunction. The potential mechanism of action within the vestibular system remains unclear; however, fluoxetine has been reported to block certain types of K + channel in other systems. Here, we investigated the direct actions of fluoxetine on membrane currents in presynaptic hair cells and postsynaptic calyx afferents of the gerbil peripheral vestibular system using whole cell patch clamp recordings in crista slices. We explored differences in K + currents in peripheral zone (PZ) and central zone (CZ) calyces of the crista and their response to fluoxetine application. Outward K + currents in PZ calyces showed greater inactivation at depolarized membrane potentials compared to CZ calyces. The application of 100 μM fluoxetine notably reduced K + currents in calyx terminals within both zones of the crista, and the remaining currents exhibited distinct traits. In PZ cells, fluoxetine inhibited a non-inactivating K + current and revealed a rapidly activating and inactivating K + current, which was sensitive to blocking by 4-aminopyridine. This was in contrast to CZ calyces, where low-voltage-activated and non-inactivating K + currents persisted following application of 100 μM fluoxetine. Additionally, marked inhibition of transient inward Na + currents by fluoxetine was observed in calyces from both crista zones. Different concentrations of fluoxetine were tested, and the EC 50 values were found to be 40 µM and 32 µM for K + and Na + currents, respectively. In contrast, 100 μM fluoxetine had no impact on voltage-dependent K + currents in mechanosensory type I and type II vestibular hair cells. In summary, micromolar concentrations of fluoxetine are expected to strongly reduce both Na + and K + conductance in afferent neurons of the peripheral vestibular system in vivo. This would lead to inhibition of action potential firing in vestibular sensory neurons and has therapeutic implications for disorders of balance.

Purpose: Amid rising health awareness, natural products which has milder effects than medical drugs are becoming popular. However, only few systems can quantitatively assess their impact on living organisms. Therefore, we developed a deep-learning system to automate the counting of cells in a gerbil model, aiming to assess a natural product's effectiveness against ischemia., Methods: The image acquired from paraffin blocks containing gerbil brains was analyzed by a deep-learning model (fine-tuned Detectron2)., Results: The counting system achieved a 79%-positive predictive value and 85%-sensitivity when visual judgment by an expert was used as ground truth., Conclusions: Our system evaluated hydrogen water's potential against ischemia and found it potentially useful, which is consistent with expert assessment. Due to natural product's milder effects, large data sets are needed for evaluation, making manual measurement labor-intensive. Hence, our system offers a promising new approach for evaluating natural products.

Helicobacter pylori is a microaerophilic Gram-negative bacterium that resides in the human stomach and is classified as a class I carcinogen for gastric cancer. Numerous studies have demonstrated that H. pylori infection plays a role in regulating the function of host cells, thereby contributing to the malignant transformation of these cells. However, H. pylori infection is a chronic process, and short-term cellular experiments may not provide a comprehensive understanding of the in vivo situation, especially when considering the lower oxygen levels in the human stomach. In this study, we aimed to investigate the mechanisms underlying gastric cell dysfunction after prolonged exposure to H. pylori under hypoxic conditions. We conducted a co-culture experiment using the gastric cell line GES-1 and H. pylori for 30 generations under intermittent hypoxic conditions. By closely monitoring cell proliferation, migration, invasion, autophagy, and apoptosis, we revealed that sustained H. pylori stimulation under hypoxic conditions significantly influences the function of GES-1 cells. This stimulation induces epithelial-mesenchymal transition and contributes to the propensity for malignant transformation of gastric cells. To confirm the in vitro results, we conducted an experiment involving Mongolian gerbils infected with H. pylori for 85 weeks. All the results strongly suggest that the Nod1 receptor signaling pathway plays a crucial role in H. pylori -related apoptosis and autophagy. In summary, continuous stimulation by H. pylori affects the functioning of gastric cells through the Nod1 receptor signaling pathway, increasing the likelihood of cell carcinogenesis. The presence of hypoxic conditions further exacerbates this process.IMPORTANCEDeciphering the collaborative effects of Helicobacter pylori infection on gastric epithelial cell function is key to unraveling the development mechanisms of gastric cancer. Prior research has solely examined the outcomes of short-term H. pylori stimulation on gastric epithelial cells under aerobic conditions, neglecting the bacterium's nature as a microaerophilic organism that leads to cancer following prolonged stomach colonization. This study mimics a more genuine in vivo infection scenario by repeatedly exposing gastric epithelial cells to H. pylori under hypoxic conditions for up to 30 generations. The results show that chronic exposure to H. pylori in hypoxia substantially increases cell migration, invasion, and epithelial-mesenchymal transition, while suppressing autophagy and apoptosis. This highlights the significance of hypoxic conditions in intensifying the carcinogenic impact of H. pylori infection. By accurately replicating the in vivo gastric environment, this study enhances our comprehension of H. pylori 's pathogenic mechanisms in gastric cancer., Competing Interests: The authors declare no conflict of interest.

Remembering what just happened is a crucial prerequisite to form long-term memories but also for establishing and maintaining working memory. So far there is no general agreement about cortical mechanisms that support short-term memory. Using a classifier-based decoding approach, we report that hippocampal activity during few sparsely distributed brief time intervals contains information about the previous sensory motor experience of rodents. These intervals are characterized by only a small increase of firing rate of only a few neurons. These low-rate predictive patterns are present in both working memory and non-working memory tasks, in two rodent species, rats and Mongolian gerbils, are strongly reduced for rats with medial entorhinal cortex lesions, and depend on the familiarity of the sensory-motor context., (© 2024 The Author(s). Hippocampus published by Wiley Periodicals LLC.)

Sensorineural hearing loss (SNHL) is the most common sensory deficit worldwide. Due to the heterogeneity of causes for SNHL, effective treatment options remain scarce, creating an unmet need for novel drugs in the field of otology. Cochlear implantation (CI) currently is the only established method to restore hearing function in profound SNHL and deaf patients. The cochlear implant bypasses the non-functioning sensory hair cells (HCs) and electrically stimulates the neurons of the cochlear nerve. CI also benefits patients with residual hearing by combined electrical and auditory stimulation. However, the insertion of an electrode array into the cochlea induces an inflammatory response, characterized by the expression of pro-inflammatory cytokines, upregulation of reactive oxygen species, and apoptosis and necrosis of HCs, putting residual hearing at risk. Here, we characterize the small molecule AC102, a pyridoindole, for its protective effects on residual hearing in CI. In a gerbil animal model of CI, AC102 significantly improves the recovery of hearing thresholds across multiple frequencies and confines the cochlear trauma to the directly mechanically injured area. In addition, AC102 significantly preserves auditory nerve fibers and inner HC synapses throughout the whole cochlea. In vitro experiments in an ethanol challenged HT22 cell-line revealed significant and dose-responsive anti-apoptotic effects following the treatment of with AC102. Further, AC102 treatment resulted in significant downregulation of the expression of pro-inflammatory cytokines in an organotypic ex vivo model of electrode insertion trauma (EIT). These results suggest that AC102's effects are likely elicited during the inflammatory phase of EIT and mediated by anti-apoptotic and anti-inflammatory properties, highlighting AC102 as a promising compound for hearing preservation during CI. Moreover, since the inflammatory response in CI shares similarities to that in other etiologies of SNHL, AC102 may be inferred as a potential general treatment option for various inner ear conditions., (© 2024. The Author(s).)

Helicobacter pylori is a common resident in the stomach of at least half of the world's population and recent evidence suggest its emergence in other organs such as the pancreas. In this organ, the presence of H. pylori DNA has been reported in cats, although the functional implications remain unknown. In this work, we determined distinct features related to the H. pylori manifestation in pancreas in a rodent model, in order to analyse its functional and structural effect. Gerbils inoculated with H. pylori exhibited the presence of this bacterium, as revealed by the expression of some virulence factors, as CagA and OMPs in stomach and pancreas, and confirmed by urease activity, bacterial culture, PCR and immunofluorescence assays. Non-apparent morphological changes were observed in pancreatic tissue of infected animals; however, delocalization of intercellular junction proteins (claudin-1, claudin-4, occludin, ZO-1, E-cadherin, β-catenin, desmoglein-2 and desmoplakin I/II) and rearrangement of the actin-cytoskeleton were exhibited. This structural damage was consistent with alterations in the distribution of insulin and glucagon, and a systemic inflammation, event demonstrated by elevated IL-8 levels. Overall, these findings indicate that H. pylori can reach the pancreas, possibly affecting its function and contributing to the development of pancreatic diseases., (© 2024. The Author(s).)

The vagus nerve regulates metabolic homeostasis and mediates gut-brain communication. We hypothesized that vagus nerve dysfunction, induced by truncated vagotomy (VGX) or carotid artery occlusion (AO), would disrupt gut-brain communication and exacerbate metabolic dysregulation, neuroinflammation, and cognitive impairment. This study aimed to test the hypothesis in gerbils fed a high-fat diet. The gerbils were divided into four groups: AO with VGX (AO&#95;VGX), AO without VGX (AO&#95;NVGX), no AO with VGX (NAO&#95;VGX), and no AO without VGX (NAO&#95;NVGX). After 5 weeks on a high-fat diet, the neuronal cell death, neurological severity, hippocampal lipids and inflammation, energy/glucose metabolism, intestinal morphology, and fecal microbiome composition were assessed. AO and VGX increased the neuronal cell death and neurological severity scores associated with increased hippocampal lipid profiles and lipid peroxidation, as well as changes in the inflammatory cytokine expression and brain-derived neurotrophic factor (BDNF) levels. AO and VGX also increased the body weight, visceral fat mass, and insulin resistance and decreased the skeletal muscle mass. The intestinal morphology and microbiome composition were altered, with an increase in the abundance of Bifidobacterium and a decrease in Akkermansia and Ruminococcus . Microbial metagenome functions were also impacted, including glutamatergic synaptic activity, glycogen synthesis, and amino acid biosynthesis. Interestingly, the effects of VGX were not significantly additive with AO, suggesting that AO inhibited the vagus nerve activity, partly offsetting the effects of VGX. In conclusion, AO and VGX exacerbated the dysregulation of energy, glucose, and lipid metabolism, neuroinflammation, and memory deficits, potentially through the modulation of the gut-brain axis. Targeting the gut-brain axis by inhibiting vagus nerve suppression represents a potential therapeutic strategy for ischemic stroke.

Circadian disruption causes glucose intolerance, cardiac fibrosis, and adipocyte dysfunction in sand rats ( Psammomys obesus ). Exercise intervention can improve glucose metabolism, insulin sensitivity, adipose tissue function and protect against inflammation. We investigated the influence of exercise on male P. obesus exposed to a short photoperiod (5 h light:19 h dark) and high-energy diet. Exercise reduced glucose intolerance. Exercise reduced cardiac expression of inflammatory marker Ccl2 and Bax : Bcl2 apoptosis ratio. Exercise increased heart:body weight ratio and hypertrophy marker Myh7 : Myh6 , yet reduced Gata4 expression. No phenotypic changes were observed in perivascular fibrosis and myocyte area. Exercise reduced visceral adipose expression of inflammatory transcription factor Rela , adipogenesis marker Ppard and browning marker Ppargc1a, but visceral adipocyte size was unaffected. Conversely, exercise reduced subcutaneous adipocyte size but did not affect any molecular mediators. Exercise increased ZT7 Bmal1 and Per2 in the suprachiasmatic nucleus and subcutaneous Per2 . Our study provides new molecular insights and histological assessments on the effect of exercise on cardiac inflammation, adipose tissue dysfunction and circadian gene expression in P. obesus exposed to short photoperiod and high-energy diet. These findings have implications for the protective benefits of exercise for shift workers in order to reduce the risk of diabetes and cardiovascular disease.

Circadian disruption increases the development of cardiovascular disease and diabetes. We found that circadian disruption causes glucose intolerance, cardiac fibrosis and adipocyte tissue dysfunction in male sand rats, Psammomys obesus . Whether these effects occur in female P. obesus is unknown. Male and female P. obesus were fed a high energy diet and exposed to a neutral (12 light:12 dark, control) or short (5 light:19 dark, circadian disruption) photoperiod for 20 weeks. Circadian disruption impaired glucose tolerance in males but not females. It also increased cardiac perivascular fibrosis and cardiac expression of inflammatory marker Ccl2 in males, with no effect in females. Females had reduced proapoptotic Bax mRNA and cardiac Myh7:Myh6 hypertrophy ratio. Cardiac protection in females occurred despite reductions in the clock gene Per2 . Circadian disruption increased adipocyte hypertrophy in both males and females. This was concomitant with a reduction in adipocyte differentiation markers Pparg and Cebpa in males and females, respectively. Circadian disruption increased visceral adipose expression of inflammatory mediators Ccl2 , Tgfb1 and Cd68 and reduced browning marker Ucp1 in males. However, these changes were not observed in females. Collectively, our study show that sex differentially influences the effects of circadian disruption on glucose tolerance, cardiac function and adipose tissue dysfunction.

Helicobacter pylori is a highly prevalent human gastric pathogen that causes gastritis, ulcer disease, and gastric cancer. It is not yet fully understood how H. pylori injures the gastric epithelium. The Na,K-ATPase, an essential transporter found in virtually all mammalian cells, has been shown to be important for maintaining the barrier function of lung and kidney epithelia. H. pylori decreases levels of Na,K-ATPase in the plasma membrane of gastric epithelial cells, and the aim of this study was to demonstrate that this reduction led to gastric injury by impairing the epithelial barrier. Similar to H. pylori infection, the inhibition of Na,K-ATPase with ouabain decreased transepithelial electrical resistance and increased paracellular permeability in cell monolayers of human gastric cultured cells, 2D human gastric organoids, and gastric epithelium isolated from gerbils. Similar effects were caused by a partial shRNA silencing of Na,K-ATPase in human gastric organoids. Both H. pylori infection and ouabain exposure disrupted organization of adherens junctions in human gastric epithelia as demonstrated by E-cadherin immunofluorescence. Functional and structural impairment of epithelial integrity with a decrease in Na,K-ATPase amount or activity provides evidence that the H. pylori -induced downregulation of Na,K-ATPase plays a role in the complex mechanism of gastric disease induced by the bacteria.

Even a transient period of hearing loss during the developmental critical period can induce long-lasting deficits in temporal and spectral perception. These perceptual deficits correlate with speech perception in humans. In gerbils, these hearing loss-induced perceptual deficits are correlated with a reduction of both ionotropic GABA A and metabotropic GABA B receptor-mediated synaptic inhibition in auditory cortex, but most research on critical period plasticity has focused on GABA A receptors. Therefore, we developed viral vectors to express proteins that would upregulate gerbil postsynaptic inhibitory receptor subunits (GABA A , Gabra1 ; GABA B , Gabbr1b ) in pyramidal neurons, and an enzyme that mediates GABA synthesis ( GAD65 ) presynaptically in parvalbumin-expressing interneurons. A transient period of developmental hearing loss during the auditory critical period significantly impaired perceptual performance on two auditory tasks: amplitude modulation depth detection and spectral modulation depth detection. We then tested the capacity of each vector to restore perceptual performance on these auditory tasks. While both GABA receptor vectors increased the amplitude of cortical inhibitory postsynaptic potentials, only viral expression of postsynaptic GABA B receptors improved perceptual thresholds to control levels. Similarly, presynaptic GAD65 expression improved perceptual performance on spectral modulation detection. These findings suggest that recovering performance on auditory perceptual tasks depends on GABA B receptor-dependent transmission at the auditory cortex parvalbumin to pyramidal synapse and point to potential therapeutic targets for developmental sensory disorders., Competing Interests: Competing interests statement:S.M. and D.H.S. submitted a patent application for the viruses used to express Gabra1 and Gabbr1b (U.S. Patent Application No. 63/359,724), and a provisional patent application for the virus to express GAD65 (U.S. Patent Provisional Application No. 63/507,894). R.F. and T.M.M. declare no competing financial interests.

This study describes the anthelmintic efficacy of an organic fraction (EtOAc-F) from Guazuma ulmifolia leaves and the evaluation of its reactive oxidative stress on Haemonchus contortus. The first step was to assess the anthelmintic effect of EtOAc-F at 0.0, 3.5, 7.0 and 14 mg kg of body weight (BW) in gerbil's (Meriones unguiculatus) artificially infected with H. contortus infective larvae (L3). The second step was to evaluate the preliminary toxicity after oral administration of the EtOAc-F in gerbils. Finally, the third step was to determine the relative expression of biomarkers such as glutathione (GPx), catalase (CAT), and superoxide dismutase (SOD) against H. contortus L3 post-exposition to EtOAc-F. Additionally, the less-polar compounds of EtOAc-F were identified by gas mass spectrophotometry (GC-MS). The highest anthelmintic efficacy (97.34%) of the organic fraction was found in the gerbils treated with the 14 mg/kg of BW. Histopathological analysis did not reveal changes in tissues. The relative expression reflects overexpression of GPx (p<0.05, fold change: 14.35) and over expression of SOD (p≤0.05, fold change: 0.18) in H. contortus L3 exposed to 97.44 mg/mL of EtOAc-F compared with negative control. The GC-MS analysis revealed the presence of 4-hydroxybenzaldehyde (1), leucoanthocyanidin derivative (2), coniferyl alcohol (3), ferulic acid methyl ester acetate (4), 2,3,4-trimethoxycinnamic acid (5) and epiyangambin (6) as major compounds. According to these results, the EtOAc-F from G. ulmifolia leaves exhibit anthelmintic effect and increased the stress biomarkers on H. contortus., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Microglia are the residential immune cells in the central nervous system. Their roles as innate immune cells and regulators of synaptic remodeling are critical to the development and the maintenance of the brain. Numerous studies have depleted microglia to elucidate their involvement in healthy and pathological conditions. PLX3397, a blocker of colony stimulating factor 1 receptor (CSF1R), is widely used to deplete mouse microglia due to its non-invasiveness and convenience. Recently, other small rodents, including Syrian hamsters (Mesocricetus auratus) and Mongolian gerbils (Meriones unguiculatus), have been recognized as valuable animal models for studying brain functions and diseases. However, whether microglia depletion via PLX3397 is feasible in these species remains unclear. Here, we administered PLX3397 orally via food pellets to hamsters and gerbils. PLX3397 successfully depleted gerbil microglia but had no effect on microglial density in hamsters. Comparative analysis of the CSF1R amino acid sequence in different species hints that amino acid substitutions in the juxtamembrane domain may potentially contribute to the inefficacy of PLX3397 in hamsters., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest associated with this manuscript., (Copyright © 2024 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

By using a unique animal model of type 2 diabetes mellitus, Psammomys obesus induced by a high-calorie diet (HCD) for nine months, we showed for the first time, in the liver, the impact of inflammation on the remodeling of intercellular junction molecules E-cadherins during the progression of steatohepatitis. Under the effect of HCD, the expressions of immunohistochemical markers, Tumor Necrosis Factor alpha (TNFα) and E-cadherins were inversely correlated. Ultrastructural examination revealed the involvement of destabilization and loss of E-cadherins in the process of hepatic pathogenesis. This mechanical maintenance stress was favored by the recruitment of immune cells which contributed to the triggering and progression of fibrosis by the enlargement of the intercellular space and the invasion of collagen fibers. Furthermore to escape cell death, loss of E-cadherins played a major role in mediating fibrosis. Psammomys obesus is a promising model for experimental research, enabling the extrapolation of observed structural and functional alterations in humans, the objective to find new therapeutic targets. The physiological resemblance between Psammomys obesus and humans enhances the precision and relevance of biomedical research efforts., Competing Interests: Declaration of interest The authors declare that they have no competing interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Aconitum coreanum (A. coreanum), a traditional Chinese medicine, has been proved to treat ischemic stroke (IS). However, the mechanisms of A. coreanum's anti-stroke is currently unknown. This study aimed to uncover the effect and mechanisms of A. coreanum. And study raw Aconitum coreanum (RA) and steamed Aconitum coreanum (SA) and Aconitum coreanum processed with ginger and Alumen (GA) on the mechanism of the pharmacological action of treating IS. Determining whether the efficacy is affected after processing. The right unilateral ligation of the carotid artery of gerbils was used to mimic IS. The neurological function score, infarct volume, oxidative stress level and inflammatory factor expression were measured in gerbils after IS. Western blot and immunofluorescence analyses were conducted to evaluate the expression of related proteins. Metabolomic analyzes IS-related metabolic pathways in urinary metabolites. RA, SA and GA significantly improved the infarct volume and behavioral score of IS gerbils, increased the expression of brain tissue superoxide dismutase (SOD), glutathione (GSH), nitric oxide (NO) and decreased the content of malondialdehyde (MDA), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α). Western blot and immunofluorescence analysis results showed that RA, SA and GA significantly increased the expression of P-Akt, PI3K, HO-1 and KEAP1. Metabolomic studies identified 112 differential metabolites, including L-Proline, Riboflavin, Leukotriene D4, and 7-Methylxanthine, as potential biomarkers of stroke, involving 14 metabolic pathways including riboflavin metabolism, pyrimidine metabolism, and purine metabolism. Our findings indicated that A. coreanum protected against cerebral ischemia injury probably via the PI3K/Akt and KEAP1/NRF2 pathway. A. coreanum before and after processing both had a protective effect against IS brain injury in gerbils. The A. coreanum efficacy was not reduced after processing. Even compared to RA, SA had better efficacy., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

With the growth of optogenetic research, the demand for optical probes tailored to specific applications is ever rising. Specifically, for applications like the coiled cochlea of the inner ear, where planar, stiff, and nonconformable probes can hardly be used, transitioning from commonly used stiff glass fibers to flexible probes is required, especially for long-term use. Following this demand, polydimethylsiloxane (PDMS) with its lower Young's modulus compared to glass fibers can serve as material of choice. Hence, the long-term usability of PDMS as a waveguide material with respect to variations in transmission and refractive index over time is investigated. Different manufacturing methods for PDMS-based flexible waveguides are established and compared with the aim to minimize optical losses and thus maximize optical output power. Finally, the waveguides with lowest optical losses (-4.8 dB cm -1 ± 1.3 dB cm -1 at 472 nm) are successfully inserted into the optogenetically modified cochlea of a Mongolian gerbil (Meriones unguiculatus), where optical stimuli delivered by the waveguides evoked robust neuronal responses in the auditory pathway., (© 2024 The Authors. Advanced Healthcare Materials published by Wiley‐VCH GmbH.)

Mitochondrial dysfunction is a significant feature of type 2 diabetes. MOTS-C, a peptide derived from mitochondria, has positive effects on metabolism and exercise capacity. This study explored the impact of high and moderate-intensity interval exercises on mitochondrial MOTS-C alterations and their correlation with metabolic markers in male diabetic sand rats. Thirty male sand rats were divided into six groups: control, MIIT, DM + HIIT, DM + MIIT, DM, and HIIT (5 rats each). Diabetes was induced using a high-fat diet (HFD) combined with streptozotocin (STZ). The Wistar sand rats in exercise groups underwent 8 weeks of interval training of varying intensities. Post sample collection, protein expressions of PCG-1a, AMPK, and GLUT4 were assessed through Western blot analysis, while MOTS-C protein expression was determined using ELISA. Both exercise intensity and diabetes significantly affected the levels of PCG-1a, MOTS-C, GLUT4 proteins, and insulin resistance (p < 0.001). The combined effect of diabetes status and exercise intensity on these levels was also significant (p < 0.001). However, the diabetes effect varied when comparing high-intensity to moderate-intensity exercise. The moderate-intensity exercise group with diabetes showed higher levels of PCG-1a, MOTS-C, and GLUT4 proteins and reduced insulin resistance levels (p < 0.001). Exercise intensity (p = 0.022) and diabetes (p = 0.008) significantly influenced AMPK protein levels. The interplay between diabetes status and exercise intensity on AMPK protein levels was noteworthy, with the moderate-intensity diabetes group exhibiting higher AMPK levels than the high-intensity diabetes group (p < 0.001). In conclusion, exercise elevates the levels of PCG-1a, MOTS-C, GLUT4, and AMPK proteins, regulating insulin resistance in diabetic sand rats. Given the AMPK-MOTS-C mitochondrial pathway's mechanisms, interval exercises might enhance the metabolic rates and general health of diabetic rodents., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Skin-penetrating parasitic nematodes infect approximately one billion people worldwide and are responsible for some of the most common neglected tropical diseases. The infective larvae of skin-penetrating nematodes are thought to search for hosts using sensory cues, yet their host-seeking behavior is poorly understood. We conducted an in-depth analysis of host seeking in the skin-penetrating human parasite Strongyloides stercoralis, and compared its behavior to that of other parasitic nematodes. We found that Str. stercoralis is highly mobile relative to other parasitic nematodes and uses a cruising strategy for finding hosts. Str. stercoralis shows robust attraction to a diverse array of human skin and sweat odorants, most of which are known mosquito attractants. Olfactory preferences of Str. stercoralis vary across life stages, suggesting a mechanism by which host seeking is limited to infective larvae. A comparison of odor-driven behavior in Str. stercoralis and six other nematode species revealed that parasite olfactory preferences reflect host specificity rather than phylogeny, suggesting an important role for olfaction in host selection. Our results may enable the development of new strategies for combating harmful nematode infections.

Giardiasis is one of the most common causes of diarrheal disease worldwide. Treatment is primarily with 5-nitro antimicrobials, particularly metronidazole. Resistance to metronidazole has been described, and treatment failures can occur in up to 20% of cases, making development of alternative antigiardials an important goal. To this end, we have screened a chemical library of 746 approved human drugs and 164 additional bioactive compounds for activity against Giardia lamblia. We identified 56 compounds that caused significant inhibition of G. lamblia growth and attachment. Of these, 15 were previously reported to have antigiardial activity, 20 were bioactive but not approved for human use, and 21 were drugs approved for human use for other indications. One notable compound of the last group was the antirheumatic drug auranofin. Further testing revealed that auranofin was active in the low (4 to 6)-micromolar range against a range of divergent G. lamblia isolates representing both human-pathogenic assemblages A and B. Most importantly, auranofin was active against multiple metronidazole-resistant strains. Mechanistically, auranofin blocked the activity of giardial thioredoxin oxidoreductase, a critical enzyme involved in maintaining normal protein function and combating oxidative damage, suggesting that this inhibition contributes to the antigiardial activity. Furthermore, auranofin was efficacious in vivo, as it eradicated infection with different G. lamblia isolates in different rodent models. These results indicate that the approved human drug auranofin could be developed as a novel agent in the armamentarium of antigiardial drugs, particularly against metronidazole-resistant strains.