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Goat may represent a valid large animal model for human pathogens and new vaccines testing. Appropriate vaccine administration is a critical component of a successful immunization program. The wrong route of administration may reduce the efficacy of the vaccine, whereas the proper administration strategy can enhance it. Viral vectors have been employed successfully for goat and sheep immunization; however, no data concerning the vaginal route are available. A viral vector's ability to transduce the site of inoculation is of primary interest. In this study, a fast and reliable ex vivo assay for testing the transduction capability of an Ad5-based vector when intravaginally administered was developed. An Ad5 vector delivering an expression cassette with a bicistronic reporter gene, Ad5-CMV-turboGFP-IRES-Luc2, was constructed. We demonstrated Ad5-CMV-turboGFP-IRES-Luc2's ability to transduce caprine vaginal mucosa by ex vivo bioluminescent imaging (BLI) employing a simple CCD camera apparatus for chemiluminescence western immunoblotting. These data, though simple, provide valuable insights into developing a vaginal immunization strategy using a viral vector-based vaccine to protect against pathogens causing genital diseases. [ABSTRACT FROM AUTHOR]

Apical periodontitis is an inflammatory condition resulting from microbial invasion in the root canal system, causing periapical tissue destruction and bone resorption. This study investigated melatonin's effects, known for its antioxidant and anti‐inflammatory properties, on experimentally induced apical periodontitis in rats. Three groups of rats were studied: control, apical periodontitis and apical periodontitis with melatonin treatment. Proinflammatory cytokines and enzyme levels in blood serum were measured, and micro‐CT analysis assessed bone resorption. Results showed significantly elevated cytokines and enzyme levels in the apical periodontitis group compared to the control. However, in the melatonin‐treated group, these levels were significantly reduced (p < 0.01–0.001). Micro‐CT analysis indicated decreased periapical resorption cavity volume and surface area with melatonin treatment. This suggests that systemic melatonin administration can mitigate inflammation and reduce bone resorption in experimentally induced apical periodontitis in rats, potentially holding promise for human endodontic disease treatment pending further research. [ABSTRACT FROM AUTHOR]

Recognizing the limitations of current therapies for Addison's disease, novel treatments that replicate dynamic physiologic corticosteroid secretion, under control of ACTH, are required. The aim of these experiments was to evaluate the feasibility of adrenocortical cell transplantation (ACT) in a large animal model, adapting methods successfully used for intracutaneous pancreatic islet cell transplantation, using a fully biodegradable temporizing matrix. Autologous porcine ACT was undertaken by bilateral adrenalectomy, cell isolation, culture, and intracutaneous injection into a skin site preprepared using a biodegradable temporizing matrix (BTM) foam. Hydrocortisone support was provided during adrenocortical cell engraftment and weaned as tolerated. Blood adrenocortical hormone concentrations were monitored, and the transplant site was examined at endpoint. Outcome measures included cellular histochemistry, systemic hormone production, and hydrocortisone independence. Transplanted adrenocortical cells showed a capability to survive and proliferate within the intracutaneous site and an ability to self-organize into discrete tissue organoids with features of the normal adrenal histologic architecture. Interpretation of systemic hormone levels was confounded by the identification of accessory adrenals and regenerative cortical tissue within the adrenal bed postmortem. Corticosteroids were unable to be completely ceased. ACT in a large animal model has not previously been attempted, yet it is an important step toward clinical translation. These results demonstrate rhe potential for ACT based on the development of adrenal organoids at the BTM site. However, the inability to achieve clinically relevant systemic hormone production suggests insufficient function, likely attributable to insufficient cells through delivered dose and subsequent proliferation. [ABSTRACT FROM AUTHOR]

Objective: Thromboangiitis obliterans (TAO) remains clinical challenging due to its rarity and underwhelming management outcomes. This study aimed to describe a novel TAO rabbit model that demonstrates a closer resemblance to TAO. Methods: Thirty-six New Zealand rabbits underwent the surgical implantation of calibrated gelatin sponge particles (CGSPs) into their right femoral artery. The CGSPs were soaked in different solutions to simulate different types of thrombi: normal (NT; normal saline); inflammatory TAO thrombus (TAO; dimethylsulfoxide [DMSO]), and DMSO with methotrexate (MTX). All groups underwent clinical assessment, digital subtraction angiography (DSA) and histopathological analysis at time points day 0 (immediate), week 1 (acute), week 2 (subacute), and week 4 (chronic). Results: The TAO rabbit presented with signs of ischemia of the right digit at week 4. On DSA, the TAO rabbits exhibited formation of corkscrew collaterals starting week 1. On H&E staining, gradual CGSP degradation was observed along with increased red blood cell aggregation and inflammatory cells migration in week 1. On week 2, disorganization of the tunica media layer and vascular smooth muscle cell (VSMC) proliferation was observed. In the TAO rabbit, migrated VSMCs, inflammatory cells, and extracellular matrix with collagen-like substances gradually occluded the lumen. On week 4, the arterial lumen of the TAO rabbit was filled with relatively-organized VSMC and endothelial cell clusters with less inflammatory cells. Neorevascularization was found in the MTX-treated group. Conclusion: The novel TAO rabbit model shows a closer resemblance to human TAO clinically, radiographically, and histopathologically. Histological analysis of the IT progression in the TAO model suggests that it is of VSMC origin. [ABSTRACT FROM AUTHOR]

Aim Methodology Results Conclusion The present study investigated the influence of apical periodontitis (AP) on the severity of rheumatoid arthritis (RA) using a Wistar rat model.Forty male Wistar rats were distributed across four groups (n = 10) based on the induction of RA and AP: Control, RA, AP, and RA + AP. RA was induced through two immunisations with type II collagen emulsified in incomplete Freund's adjuvant, followed by one immunisation with complete Freund's adjuvant. After 21 days of RA induction, AP was induced by exposing the pulp of four molars. Animals were euthanized after 28 days of pulp exposure. Through the experiment, visual and behavioural assessments tracked RA development and the knees and hind paw joints were measured. Micro‐computed tomography scans of knees and hind paws, as well as mandibles and maxillae, were conducted to evaluate RA severity and the presence of AP, respectively. Serum samples were collected to analyse proinflammatory cytokines (IL‐1β, IL‐2, IL‐17, and TNF‐α). Non‐parametric data were analysed using the Kruskal‐Wallis test followed by Student–Newman–Keuls test, while one‐way anova followed by Tukey's test was performed for parametric data. A significance level of 5% was employed.All molars submitted to access cavity developed AP. All joints subjected to arthritis induction developed the disease, with AP + RA demonstrating a higher arthritis severity when compared to the RA group (p < .05). RA + AP group displayed a significantly larger hind paw and knee circumference compared to the RA group (p < .05). Micro‐CT images of RA and RA + AP groups revealed joints with erosions and bone deformities, with a significantly lower bone surface density, lower trabecular number and higher trabecular separation in the hind paw and a significantly lower percent bone volume and higher trabecular separation in the knees of RA + AP group compared to RA group (p < .05). RA + AP group exhibited a significantly higher level of TNF‐α and a lower level of IL‐2 compared to all other groups (p < .05). Both RA and RA + AP groups had significantly higher IL‐17 levels (p < .05), while there was no significant difference in IL‐1β levels among the groups (p > .05).The findings from this study underscore a possible relationship between apical periodontitis and the exacerbation of rheumatoid arthritis. [ABSTRACT FROM AUTHOR]

Background Objective Methods Results Conclusion Current animal models of sensitive skin do not adequately reflect the objective symptoms or physiological manifestations observed in human sensitive skin.To construct and validate a sensitive skin model in mice.Tape stripping (TS) was used to induce partial mechanical disruption of the lipid film and stratum corneum. Subsequently, propylene glycol (PG) was applied to disrupt the lipid structure in the skin barrier, and capsaicin (CS) activate transient receptor potential vanilloid 1 (TRPV1) receptors of keratinocytes to simulate the formation of sensitive skin. Evident itching and tingling sensations, scaly skin, vasodilation, local congestion, increased transepidermal water loss (TEWL), elevated TRPV1 expression, and inflammatory symptoms were subsequently evaluated.TS combined with PG and CS application resulted in skin flakes; skin barrier disruption; vascular dilation; increased itching, stinging, and inflammation; TRPV1 upregulation in the epidermis; and a significant increase in lactic acid‐induced itching and stinging.Using a combination of TS and PG, and CS application, a mouse model of sensitive skin was successfully established involving various skin phenotypes and physiological manifestations, including skin flakes, vasodilation, increased blood flow and TEWL, itching and stinging sensations, inflammation, and elevated TRPV1 expression. [ABSTRACT FROM AUTHOR]

Introduction: Spinal cord injury (SCI) animal models often utilize an open surgical laminectomy, which results in animal morbidity and also leads to changes in spinal canal diameter, spinal cord perfusion, cerebrospinal fluid flow dynamics, and spinal stability which may confound SCI research. Moreover, the use of open surgical laminectomy for injury creation lacks realism when considering human SCI scenarios. Methods: We developed a novel, image-guided, minimally invasive, large animal model of SCI which utilizes a kyphoplasty balloon inserted into the epidural space via an interlaminar approach without the need for open surgery. Results: The model was validated in 5 Yucatán pigs with imaging, neurofunctional, histologic, and electrophysiologic findings consistent with a mild compression injury. Discussion: Few large animal models exist that have the potential to reproduce the mechanisms of spinal cord injury (SCI) commonly seen in humans, which in turn limits the relevance and applicability of SCI translational research. SCI research relies heavily on animal models, which typically involve an open surgical, dorsal laminectomy which is inherently invasive and may have untoward consequences on animal morbidity and spinal physiology that limit translational impact. We developed a minimally invasive, large animal model of spinal cord injury which utilizes a kyphoplasty balloon inserted percutaneously into the spinal epidural space. Balloon inflation results in a targeted, compressive spinal cord injury with histological and electrophysiological features directly relevant to human spinal cord injury cases without the need for invasive surgery. Balloon inflation pressure, length of time that balloon remains inflated, and speed of inflation may be modified to achieve variations in injury severity and subtype. [ABSTRACT FROM AUTHOR]

Introduction: Alzheimer’s disease (AD) and other forms of dementia have a devastating effect on the community and healthcare system, as neurodegenerative diseases are causing disability and dependency in older population. Pharmacological treatment options are limited to symptomatic alleviation of cholinergic deficit and accelerated clearance of β-amyloid aggregates, but accessible disease-modifying interventions are needed especially in the early phase of AD. Melatonin was previously demonstrated to improve cognitive function in clinical setting and experimental studies also. Methods: In this study, the influence of melatonin supplementation was studied on behavioral parameters and morphological aspects of the hippocampus and amygdala of rats. Streptozotocin (STZ) was injected intracerebroventricularly to induce AD-like symptoms in male adult Wistar rats (n = 18) which were compared to age-matched, sham-operated animals (n = 16). Melatonin was administered once daily in a dose of 20 mg/kg body weight by oral route. Behavioral analysis included open-field, novel object recognition, and radial-arm maze tests. TNF-α and MMP-9 levels were determined from blood samples to assess the anti-inflammatory and neuroprotective effects of melatonin. Immunohistological staining of brain sections was performed using anti-NeuN, anti-IBA-1, and anti-GFAP primary antibodies to evaluate the cellular reorganization of hippocampus. Results and Discussion: The results show that after 40 days of treatment, melatonin improved the cognitive performance of STZ-induced rats and reduced the activation of microglia in both CA1 and CA3 regions of the hippocampus. STZ-injected animals had higher levels of GFAP-labeled astrocytes in the CA1 region, but melatonin treatment reduced this to that of the control group. In conclusion, melatonin may be a potential therapeutic option for treating AD-like cognitive decline and neuroinflammation. [ABSTRACT FROM AUTHOR]

BACKGROUND: As a dominant breed pig in southwest China, the southern Yunnan small-ear pig has been widely used as an experimental animal in the basic research of other disciplines, but there are still no reports on its application in anterior cruciate ligament reconstruction. OBJECTIVE: To establish a large animal model of the southern Yunnan small-ear pig with anterior cruciate ligament with autologous Achilles tendon was established. METHODS: Twenty adult female Yunnan small-ear pigs were equally randomized into two groups. In the autologous Achilles tendon group, the right knee anterior cruciate ligament was reconstructed with autologous Achilles tendon as a graft, while in the sham-operated group, a similar operation was performed on the right knee without any treatment of the anterior cruciate ligament. General conditions of each pig were observed and recorded before and 12 months after surgery. Ligaments and grafts were taken for gross observation and MAS scoring. Hematoxylin-eosin staining was performed to observe morphological characteristics of ligaments. The staining and arrangement of type I and type III collagen were evaluated by immunohistochemistry. Transmission electron microscopy was used to observe the type, size, diameter, ratio, and distribution of collagen fibers in ligaments. RESULTS AND CONCLUSION: All animals had normal diet and activity, good wound healing, no obvious inflammatory reaction, no local purulent infection, and no significant changes in mental and urinary conditions compared with those before surgery. The reconstructed cruciate ligament of the knee was intact, with no stiffness and normal range of motion. Both the anterior drawer and Lachman tests were negative. Gross observation of the graft: 12 months after surgery, the grafts was in good position, with good integrity, obvious tension, ligament color close to the original anterior cruciate ligament, and complete surface synovial coverage. Most of the intraarticular ligaments in the autologous Achilles tendon group were defined as MAS I type and a few were defined as MAS II type. In the sham-operated group, the intraarticular ligament was defined as MAS I type. Hematoxylin-eosin staining indicated that, 12 months after surgery, collagen fibers in the autologous Achilles tendon group began to appear bundled, isotropic, and uniformly arranged, with more obvious isotropic corrugations, and the nuclei were mainly linear or spindle-shaped, which were similar to those in normal anterior cruciate ligament tissue of the sham-operated group. Immunohistochemistry results indicated that, 12 months after surgery, there was a higher expression of type I collagen and significantly less expression of type III collagen in the reconstructed anterior cruciate ligament in the autologous Achilles tendon group. The degree of type I and type III staining was similar in the two groups. Under the transmission electron microscope, the diameter, arrangement and density of collagen fibers in the reconstructed anterior cruciate ligament of the autologous Achilles tendon group were similar to those of the original anterior cruciate ligament at 12 months after surgery, indicating that the ligament remodeling process had been basically completed in the autologous Achilles tendon group at 12 months after surgery. Through a comprehensive evaluation of animal general conditions, ligament general view, MAS score, hematoxylin-eosin staining, immunohistochemistry, and transmission electron microscopy observation, we successfully established a large animal model of anterior cruciate ligament reconstruction using autogenous Achilles tendon in southern Yunnan small-ear pigs, with good morphological, histological and ultrastructural results. [ABSTRACT FROM AUTHOR]

Simple Summary: Depilation is a well-established method for synchronizing the hair growth in mice which is valuable to test hair growth interventions. However, our experience with the previously published depilation protocols showed that upon depilation mice developed wounds. Here, we propose a new depilation method that protects the mouse skin, minimizing skin injuries and improving not only experimental conditions but also animal welfare. We test this new protocol not only in C57BL/6J mice, the most commonly used strain in hair growth pre-clinical studies, but also in other two strains (Sv129 and B6129F1), which lack a well-characterized hair growth cycle. Our results show that hair cycle kinetics are similar in all the analyzed strains, but Sv129 and B6129F1 skins are morphologically different from C57BL/6J skin, presenting increased number and size of hair follicles in anagen, consistent to the higher hair density observed macroscopically. This study reveals a new method to improve animal hair research and characterizes the hair growth in two different strains, enhancing their suitability in future studies. In mice, hair growth follows a mosaic or wavy patterning. Therefore, synchronization of the hair growth cycle is required to adequately evaluate any trichogenic interventions pre-clinically. Depilation is the established method for synchronizing the growth phase of mouse hair follicles. When attempting to reproduce procedures reported in the literature, C57BL/6J mice developed severe wounds. This led us not only to optimize the procedure, but also to test the procedure in other strains, namely Sv129 and the F1 generation from C57BL/6J crossed with Sv129 (B6129F1 mixed background), for which the hair growth cycle has not been ascertained yet. Here, we describe an optimized depilation procedure, using cold wax and an extra step to protect the animal skin that minimizes injury, improving experimental conditions and animal welfare in all strains. Moreover, our results show that, although hair cycle kinetics are similar in all the analyzed strains, Sv129 and B6129F1 skins are morphologically different from C57BL/6J skin, presenting an increased number and size of hair follicles in anagen, consistent to the higher hair density observed macroscopically. Altogether, the results disclose an optimized mouse depilation method that excludes the detrimental and confounding effects of skin injury in hair growth studies and reveals the hair cycle features of other mouse strains, supporting their use in hair growth pre-clinical studies. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social interaction and communication, anxiety, hyperactivity, and interest restricted to specific subjects. In addition to the genetic factors, multiple environmental factors have been related to the development of ASD. Animal models can serve as crucial tools for understanding the complexity of ASD. In this study, a chemical model of ASD has been developed in zebrafish by exposing embryos to valproic acid (VPA) from 4 to 48 h post-fertilization, rearing them to the adult stage in fish water. For the first time, an integrative approach combining behavioral analysis and neurotransmitters profile has been used for determining the effects of early-life exposure to VPA both in the larval and adult stages. Larvae from VPA-treated embryos showed hyperactivity and decreased visual and vibrational escape responses, as well as an altered neurotransmitters profile, with increased glutamate and decreased acetylcholine and norepinephrine levels. Adults from VPA-treated embryos exhibited impaired social behavior characterized by larger shoal sizes and a decreased interest for their conspecifics. A neurotransmitter analysis revealed a significant decrease in dopamine and GABA levels in the brain. These results support the potential predictive validity of this model for ASD research. [ABSTRACT FROM AUTHOR]

Oral squamous cell carcinoma (OSCC) is a highly prevalent and aggressive malignancy, with mortality rates reaching 60%, mainly due to its excessive diagnostic delay. MiRNAs, a class of crucial epigenetic gene-expression regulators, have emerged as potential diagnostic biomarkers, with >200 molecules exhibiting expressional dysregulation in OSCC. We had previously established an in silico methodology for the identification of the most disease-specific molecules by bridging genetics and epigenetics. Here, we identified the stage-specific miRNAs that govern the asymptomatic early stages of oral tumorigenesis by exploiting seed-matching and the reverse interplay between miRNA levels and their target genes' expression. Incorporating gene-expression data from our group's experimental hamster model of sequential oral oncogenesis, we bioinformatically detected the miRNAs that simultaneously target/regulate >75% of the genes that are characteristically upregulated or downregulated in the consecutive stages of hyperplasia, dysplasia, and early invasion, while exhibiting the opposite expressional dysregulation in OSCC-derived tissue and/or saliva specimens. We found that all stages share the downregulation of miR-34a-5p, miR124-3p, and miR-125b-5p, while miR-1-3p is under-expressed in dysplasia and early invasion. The malignant early-invasion stage is distinguished by the downregulation of miR-147a and the overexpression of miR-155-5p, miR-423-3p, and miR-34a-5p. The identification of stage-specific miRNAs may facilitate their utilization as biomarkers for presymptomatic OSCC diagnosis. [ABSTRACT FROM AUTHOR]

Objective: Immunotherapy, specifically immune checkpoint inhibitors (ICIs), has revolutionized cancer treatment. However, it can also cause immune‐related adverse events (irAEs). This study aimed to develop a clinically practical animal model of irAEs using BALB/c mice. Methods: Subcutaneous tumors of mouse breast cancer 4T1 cells were generated in inbred BALB/c mice. The mice were treated with programmed death‐1 (PD‐1) and cytotoxic t‐lymphocyte antigen 4 (CTLA‐4) inhibitors once every 3 days for five consecutive administration cycles. Changes in tumor volume and body weight were recorded. Lung computed tomography (CT) scans were conducted. The liver, lungs, heart, and colon tissues of the mice were stained with hematoxylin–eosin (H&E) staining to observe inflammatory infiltration and were scored. Serum samples were collected, and enzyme‐linked immunosorbent assay (ELISA) was used to detect the levels of ferritin, glutamic‐pyruvic transaminase (ALT), tumor necrosis factor‐α (TNF‐α), interferon‐gamma (IFN‐γ), and interleukin‐6 (IL‐6). Mouse liver and lung cell suspensions were prepared, and changes in macrophages, T cells, myeloid‐derived suppressor cells (MDSCs), and regulatory (Treg) cells were detected by flow cytometry. Results: Mice treated with PD‐1 and CTLA‐4 inhibitors showed significant reductions in tumor volume and body weight. The tissue inflammatory scores in the experimental group were significantly higher than those in the control group. Lung CT scans of mice in the experimental group showed obvious inflammatory spots. Serum levels of ferritin, IL‐6, TNF‐α, IFN‐γ, and ALT were significantly elevated in the experimental group. Flow cytometry analysis revealed a substantial increase in CD3+T cells, Treg cells, and macrophages in the liver and lung tissues of mice in the experimental group compared with the control group, and the change trend of MDSCs was opposite. Conclusions: The irAE‐related animal model was successfully established in BALB/c mice using a combination of PD‐1 and CTLA‐4 inhibitors through multiple administrations with clinical translational value and practical. This model offers valuable insights into irAE mechanisms for further investigation. [ABSTRACT FROM AUTHOR]

Aim Methodology Results Conclusions To evaluate the effect of systemic administration of propranolol on the severity of apical periodontitis (AP) in chronically stressed rats.Twenty‐four 70‐day‐old male Wistar rats (Rattus norvegicus, albinus) were distributed into three groups (n = 8): rats with AP without stressful conditions (AP‐Control), rats with AP and submitted to a chronic unpredictable stress (CUS) protocol (AP + S) and rats with AP and submitted to a CUS protocol treated with propranolol (AP + S + PRO). Stress procedures were applied daily until the end of the experiment. After 3 weeks of CUS, AP was induced in all groups by exposing the pulpal tissue of mandibular and maxillary first molars to the oral environment. Propranolol treatment was administered orally once a day for the entire period of the experiment. Rats were sacrificed at 42 days, and the blood was collected for stress biomarkers serum dosage by multiplex assay. Mandibles were removed and submitted to microtomography and histopathological analyses. Periapical tissue surrounding the upper first molar was homogenized and subjected to RT‐PCR analysis to evaluate the mRNA expression of RANKL, TRAP and OPG. Parametric data were assessed using one‐way ANOVA followed by Tukey's test while the nonparametric data were analysed by the Kruskal–Wallis followed by Dunn's test. Significance level was set at 5% (p < .05) for all assessed parameters.Micro‐CT revealed statistically significant differences in bone resorption which was greater in the AP + S group (p < .05), but no differences were observed between the Control and AP + S + PRO groups (p > .05). The AP + S + PRO group had a lower intensity and extent of inflammatory infiltrate compared to the AP + S group with smaller areas of bone loss (p < 0.05). The gene expression of RANKL and TRAP was significantly higher in the stressed group AP + S compared to the control group (p < .05), and a significantly higher OPG expression was observed in AP + S + PRO compared to the AP + S group (p < .05).Oral administration of propranolol had a significant effect on the AP severity in stressed rats, suggesting an anti‐inflammatory effect and a protective role on bone resorption of AP in stressed animals. Further research is necessary to fully comprehend the underlying mechanisms. [ABSTRACT FROM AUTHOR]

Background: Extracellular matrix (ECM) remodeling in skeletal muscle is a significant factor in the development of sarcopenia. This study aims to evaluate changes in ECM remodeling in the lumbar paravertebral muscles of sarcopenic rats using diffusion-tensor magnetic resonance imaging (DT-MRI) and compare them with histology. Methods: Twenty 6-month-old female Sprague Dawley rats were randomly divided into the dexamethasone (DEX) group and the control (CON) group. Both groups underwent 3.0T MRI scanning, including Mensa, T2WI, and DT-MRI sequences. The changes in muscle fibers and extracellular matrix (ECM) of the erector spinal muscle were observed using hematoxylineosin and sirius red staining. The expressions of collagen I, III, and fibronectin in the erector spinae were detected by western blot. Pearson correlation analysis was employed to assess the correlation between MRI quantitative parameters and corresponding histopathology markers. Results: The cross-sectional area and fractional anisotropy values of the erector spinae in the DEX group rats were significantly lower than those in the CON group (p < 0.05). Hematoxylin eosin staining revealed muscle fiber atrophy and disordered arrangement in the DEX group, while sirius red staining showed a significant increase in collagen volume fraction in the DEX group. The western blot results indicate a significant increase in the expression of collagen I, collagen III, and fibronectin in the DEX group (p < 0.001 for all). Correlation coefficients between fractional anisotropy values and collagen volume fraction, collagen I, collagen III, and fibronectin were − 0.71, -0.94, -0.85, and − 0.88, respectively (p < 0.05 for all). Conclusions: The fractional anisotropy value is strongly correlated with the pathological collagen volume fraction, collagen I, collagen III, and fibronectin. This indicates that DT-MRI can non-invasively evaluate the changes in extracellular matrix remodeling in the erector spinal muscle of sarcopenia. It provides a potential imaging biomarker for the diagnosis of sarcopenia. [ABSTRACT FROM AUTHOR]

Background: Perforator dissection can be technically demanding with a steep learning curve. Surgical training during the spare time was vital to compensate for inadequate clinical exposure. The objective of this study was to explore a home do-it-yourself model for flap training. Methods: The artery and vein of ten porcine hindlimb were infused with black-colored latex and red-colored latex, respectively. The distribution of obvious perforators in the skin was carefully observed. The retrograde anatomy of each perforator was carefully determined to explore its source artery. Perforator flap planning and dissection were conducted on 5 hindlimb. Results: It was observed that there were three obvious perforators that were primarily located in the lateral, anterolateral and posterior sides of the thigh. Retrograde anatomy showed that the three perforators originated from two source arteries: the femoral profound artery and the superficial circumflex iliac artery. Based on the two source arteries, we named the three perforator flaps as follows: the superficial circumflex iliac artery flap, the profunda artery perforator flap in the posterior femoral region, and the profunda artery perforator flap in the lateral femoral region. All of the three perforator flaps can be easily located and harvest in a convenient position. Conclusions: The porcine thigh was an ideal cadaveric animal model for flap training. These three newly described porcine perforator flap models were easy to replicate at home without the need for an ethics license or for anesthesia. Level of Evidence: Not gradable. [ABSTRACT FROM AUTHOR]

The filamentous bacteriophage M13KO7 (M13) is the most used in phage display (PD) technology and, like other phages, has been applied in several areas of medicine, agriculture, and in the food industry. One of the advantages is that they can modulate the immune response in the presence of pathogenic microorganisms, such as bacteria and viruses. This study evaluated the use of phage M13 in the chicken embryos model. We inoculated 13-day-old chicken embryos with Salmonella Pullorum (SP) and then evaluated survival for the presence of phage M13 or E. coli ER2738 (ECR) infected with M13. We found that the ECR bacterium inhibits SP multiplication in 0.32 (M13-infected ECR) or 0.44 log UFC/mL (M13-uninfected ECR) and that the ECR-free phage M13 from the PD library can be used in chicken embryo models. This work provides the use of the chicken embryo as a model to study systemic infection and can be employed as an analysis tool for various peptides that M13 can express from PD selection. Key points: • SP-infected chicken embryo can be a helpful model of systemic infection for different tests. • Phage M13 does not lead to embryonic mortality or cause serious injury to embryos. • Phage M13 from the PD library can be used in chicken embryo model tests. [ABSTRACT FROM AUTHOR]

Sialadenitis and sialadenitis-induced sialopathy are typically caused by obstruction of the salivary gland ducts. Atrophy of the salivary glands in experimental animals caused by duct ligation exhibits a histopathology similar to that of salivary gland sialadenitis. Therefore, a variety of duct ligation/deligation models have been commonly employed to study salivary gland injury and regeneration. Duct ligation is mainly characterised by apoptosis and activation of different signaling pathways in parenchymal cells, which eventually leads to gland atrophy and progressive dysfunction. By contrast, duct de-ligation can initiate the recovery of gland structure and function by regenerating the secretory tissue. This review summarizes the animal duct ligation/de-ligation models that have been used for the examination of pathological fundamentals in salivary disorders, in order to unravel the pathological changes and underlying mechanisms involved in salivary gland injury and regeneration. These experimental models have contributed to developing effective and curative strategies for gland dysfunction and providing plausible solutions for overcoming salivary disorders. [ABSTRACT FROM AUTHOR]

Dysbindin-1, a protein encoded by the schizophrenia susceptibility gene DTNBP1, is reduced in the hippocampus of schizophrenia patients. It is expressed in various cellular populations of the brain and implicated in dopaminergic and glutamatergic transmission. To investigate the impact of reduced dysbindin-1 in excitatory cells on hippocampal-associated behaviors and synaptic transmission, we developed a conditional knockout mouse model with deletion of dysbindin-1 gene in CaMKIIα expressing cells. We found that dysbindin-1 reduction in CaMKII expressing cells resulted in impaired spatial and social memories, and attenuation of the effects of glutamate N-methyl-d-asparate receptor (NMDAR) antagonist MK801 on locomotor activity and prepulse inhibition of startle (PPI). Dysbindin-1 deficiency in CaMKII expressing cells also resulted in reduced protein levels of NMDAR subunit GluN1 and GluN2B. These changes were associated with increased expression of immature dendritic spines in basiliar dendrites and abnormalities in excitatory synaptic transmission in the ventral hippocampus. These results highlight the functional relevance of dysbindin-1 in excitatory cells and its implication in schizophrenia-related pathologies. [ABSTRACT FROM AUTHOR]

Aim Methodology Results Conclusion In this study, we investigated the systemic implications of chronic apical periodontitis (CAP). CAP may contribute to the nonalcoholic fatty liver disease (NAFLD) progression through the gut microbiota and its metabolites, which are related to the degree of fibrosis.Sixteen 7‐week‐old male apolipoprotein E knockout (apoE−/−) mice were randomly divided into two groups: the CAP and Con groups. A CAP model was established by sealing the first‐ and second‐maxillary molars with bacterium‐containing cotton balls. Apical lesions were evaluated by micro‐CT. Histological evaluations of NAFLD were performed using second harmonic generation/two‐photon excitation fluorescence (SHG/TPEF) assays. Additionally, we comprehensively analyzed the gut microbiota using 16S rRNA gene sequencing and explored metabolic profiles by liquid chromatography–mass spectrometry (LC–MS). Immunofluorescence analysis was used to examine the impact of CAP on tight junction proteins and mucin expression. Transcriptome assays have elucidated gene expression alterations in liver tissues.Micro‐CT scans revealed an evident periapical bone loss in the CAP group, and the total collagen percentage was increased (Con, 0.0361 ± 0.00510%, CAP, 0.0589 ± 0.00731%, p < .05). 16S rRNA sequencing revealed reduced diversity and distinct taxonomic enrichment in the CAP group. Metabolomic assessments revealed that differentially enriched metabolites, including D‐galactosamine, were enriched and that 16‐hydroxyhexadecanoic acid and 3‐methylindole were depleted in the CAP group. Immunofluorescence analyses revealed disruptions in tight junction proteins and mucin production, indicating intestinal barrier integrity disruption. Liver transcriptome analysis revealed upregulation of Lpin‐1 expression in the CAP group.This study provides comprehensive evidence of the systemic effects of CAP on liver fibrosis in NAFLD patients by elucidating alterations in the gut microbiota composition and metabolism. [ABSTRACT FROM AUTHOR]

Chemotherapeutic drugs have demonstrated effectiveness in treating various neoplastic conditions; however, they can also have detrimental effects on male gonadal function and fertility. Consequently, interest has grown in identifying novel approaches that can mitigate chemotherapy-induced testicular damage. Thymoquinone (TQ), the chief active component of the volatile oil of Nigella sativa (NS), has a wide range of therapeutic properties, including antioxidant, anti-inflammatory and anti-apoptotic effects. The aim of this systematic review was to identify experimental animal studies that have evaluated the protective effects of TQ against testicular complications associated with chemotherapy. In accordance with the preferred reporting items for systematic review and meta-analyses (PRISMA) guidelines, a thorough search was performed across several databases (PubMed, EBSCOhost, Sage and Scopus) to identify experimental studies published from 2010 to May 2022 that focused on rodent models and compared the effects of TQ versus other chemotherapeutic drugs. Eight studies met the inclusion criteria, comparing TQ with methotrexate (MTX), 6-mercaptopurine (6-MP), cyclophosphamide (CPA), bleomycin (BL), doxorubicin (DOX) or busulfan (BUS). The results of these studies consistently demonstrated that TQ significantly improved sperm parameters, the levels of oxidative stress (OS) markers, apoptosis markers, and hormones and testicular histopathology, indicating that TQ has protective effects against chemotherapy-induced damage. TQ mitigated chemotherapy-induced testicular toxicity by decreasing lipid peroxidation and enhancing the activity of antioxidant enzymes within chemotherapy-treated testes. These findings highlight the potential of TQ as a therapeutic agent that can ameliorate testicular complications associated with chemotherapy, thereby providing a basis for further research and potential therapeutic applications. [ABSTRACT FROM AUTHOR]

Seizures and epilepsy affect people of all sexes and genders. In the last several years, funding agency initiatives such as the U.S. National Institutes of Health policy on sex as a biological variable (SABV) have intended to encourage researchers to study both males and females from cell to tissue to organism and analyze and report the resulting data with sex as a factor. Preclinical epilepsy research, however, continues to be plagued by confusion regarding both the SABV policy and its implementation, reflecting similar beliefs in the larger neuroscience research community. This article aims to address some common misconceptions and provide practical tools and suggestions for preclinical epilepsy researchers in implementing SABV and analysis of the female ovarian cycle (estrous cycle in rodents) in their research programs, with a focus on studies using rodent models. Examples of recent publications in preclinical epilepsy research highlighting the value of incorporating SABV and information on the estrous cycle are included. The specifics of how best to address SABV and the estrous cycle can vary depending on the needs and goals of a particular research program, but an embrace of these physiological factors by the preclinical epilepsy research community promises to yield more rigorous research and improved treatment strategies for all people with epilepsy. [ABSTRACT FROM AUTHOR]

Introduction: Nosocomial meningitis may occur after procedures affecting the central nervous system or following traumatic injury. The causative infectious organism is commonly Staphylococcus aureus, a Gram-positive bacterium. The aim of the present study was to compare the effectiveness of two antibacterial agents, ceftobiprole and vancomycin, in an animal model of methicillin-resistant S. aureus (MRSA) meningitis. Method: The strain of MRSA used was ATCC 43300. The animals were divided into three groups and infected intracisternally with MRSA. Controls received no antibiotherapy while the ceftobiprole group received 25 mg/kg and the vancomycin group received 20 mg/kg intravenously. Blood and cerebrospinal fluid (CSF) samples were collected at three time points. All animals were euthanized at 73 h after start of treatment. Results: There was a significant difference (p < 0.05) between both treatment groups and the control animals at 24 h (drug trough) and 73 h (1 h after third dose) after start of treatment in terms of CSF bacterial levels. At 73 h, there was a significant difference in survival between the control group and the two treatment groups but no difference between the treated animal survival rates. Conclusion: Intravenous treatment with ceftobiprole and vancomycin appears to be equally effective in a rabbit model of MRSA meningitis. [ABSTRACT FROM AUTHOR]

Introduction: Cupping therapy has been widely utilized as a complementary therapy, including in the treatment of stroke. This study aims to compare the effects of wet cupping therapy and exercise on brain-derived neurotrophic factor (BDNF) expression in animal models of stroke. Materials and methods: This study employed a post-test-only control group design. Twenty-four 3-month-old male Wistar rats were divided into four groups: sham group (n=6), stroke group (n=6), stroke+cupping group (n=6), and stroke+exercise group (n=6). Stroke animal models were induced by unilateral common carotid artery occlusion (UCCAO). Wet cupping therapy was administered twice a week for three weeks to the stroke+cupping group. In contrast, the stroke+exercise group participated in swimming activities scheduled for 20 minutes per day, three times a week over the same three-week period. Results: The mean of nerve cells expressing BDNF in the sham group was 41.33±22.17; the stroke group was 17.66±11.03; the stroke+cupping group was 24.50±26.82; and the stroke+exercise group was 60.16±30.94. Analysis of multiple comparisons among groups proved that there were no significant differences in BDNF expression between the stroke and sham group (p=0.102) and between the stroke+cupping and stroke group (p=0.626). Meanwhile, the BDNF expression in the stroke+exercise group was significantly higher than in the stroke group (p=0.06). Apart from that, the BDNF expression in the stroke+exercise group was significantly higher than stroke+ cupping group (p=0.018). Conclusion: In the stroke animal model, exercise demonstrated greater efficacy in upregulating the expression of BDNF compared to wet cupping therapy. [ABSTRACT FROM AUTHOR]

Animal body coloration is often linked to social dominance and mating success. This is because it can carry information on an animal's body condition and competitive ability by reflecting the genetic quality of individuals or by responding to their current or past living conditions. The present study investigates genetic and environmental effects on a conspicuous color pattern of the cichlid fish Tropheus sp. black "Ikola," in which the size of a carotenoid‐based yellow area on the body co‐varies with social dominance. To examine environmental plasticity of the color pattern, we tested for effects of early‐life stress, induced by reduced feeding of juveniles prior to color pattern formation, as well as effects of a stress treatment administered to fully colored adult fish. None of the stress treatments affected the color pattern as quantified by the width of the yellow bar. However, offspring bar width was correlated to parental values in mid‐parent‐mid‐offspring regression analyses, and animal models estimated significant additive genetic effects on bar width, indicating heritability of the trait. Depending on the random effects structure of the animal models (i.e., whether including or excluding maternal and brood effects), narrow‐sense heritability estimates for bar width ranged between 0.2 and 0.8, with the strongest statistical support for the highest estimate. In each of the alternative models, a large proportion of the total variance in bar width was explained by the included random effects, suggesting that bar width is strongly determined by genetic factors or shared maternal and brood environments, with limited scope for environmental influences later in life. [ABSTRACT FROM AUTHOR]

Simple Summary: Therapies to prevent osteoporosis are relevant since it is one of the most common non-communicable human diseases in the world and the most prevalent bone disorder in adults. Jaboticaba is a small, round fruit with white pulp and purple peel that concentrates compounds that may have therapeutic applications. Since jaboticaba peel extract (JPE) enhances the activity of osteoblasts (the cells that form bone) under osteoporotic conditions, we hypothesized that JPE prevents the development of osteoporosis induced by the removal of the ovaries. Ovariectomized rats were treated with either JPE (30 mg/kg of body weight) or its vehicle for 90 days, starting 7 days after the ovariectomy. JPE attenuated ovariectomy-induced bone loss due to its ability to prevent the imbalance between osteoblast and adipocyte (the cells that produce bone and fat, respectively) differentiation. These data indicate the potential therapeutic use of JPE to prevent osteoporosis. Therapies to prevent osteoporosis are relevant since it is one of the most common non-communicable human diseases in the world and the most prevalent bone disorder in adults. Since jaboticaba peel extract (JPE) added to the culture medium enhanced the osteogenic potential of mesenchymal stem cells (MSCs) derived from osteoporotic rats, we hypothesized that JPE prevents the development of ovariectomy-induced osteoporosis. Ovariectomized rats were treated with either JPE (30 mg/kg of body weight) or its vehicle for 90 days, starting 7 days after the ovariectomy. Then, the femurs were subjected to microcomputed tomography and histological analyses, and the osteoblast and adipocyte differentiation of MSCs was evaluated. JPE attenuated ovariectomy-induced bone loss, as evidenced by higher bone volume/total volume and trabecular number, along with lower trabecular separation and bone marrow adiposity. These protective effects of JPE on bone tissue are due to its ability to prevent the imbalance between osteoblast and adipocyte differentiation of MSCs, since, compared with MSCs derived from ovariectomized rats treated with vehicle, MSCs treated with JPE exhibited higher gene and protein expression of osteogenic markers and extracellular matrix mineralization, as well as lower gene expression of adipogenic markers. These data highlight the potential therapeutic use of JPE to prevent osteoporosis. [ABSTRACT FROM AUTHOR]

The neural connectivity among the oral cavity, pharynx, and esophagus is a critical component of infant feeding physiology. Central integration of oral and pharyngeal afferents alters motor outputs to structures that power swallowing, but the potential effects of esophageal afferents on preesophageal feeding physiology are unclear. These effects may explain the prevalence of oropharyngeal dysphagia in infants suffering from gastroesophageal reflux (GER), though the mechanism underlying this relationship remains unknown. Here we use the validated infant pig model to assess the impacts of simulated GER on preesophageal feeding parameters. We used high-speed videofluoroscopy and electromyography to record bottle-feeding before and following the infusion of a capsaicin-containing solution into the lower esophagus. Sucking parameters were minimally affected by capsaicin exposure, such that genioglossus activity was unchanged and tongue kinematics were largely unaffected. Aspects of the pharyngeal swallow were altered with simulated GER, including increased thyrohyoid muscle activity, increased excursions of the hyoid and thyroid per swallow, decreased swallow frequency, and increased bolus sizes. These results suggest that esophageal afferents can elicit changes in pharyngeal swallowing. In addition, decreased swallowing frequency may be the mechanism by which esophageal pathologies induce oropharyngeal dysphagia. Although recent work indicates that oral or pharyngeal capsaicin may improve dysphagia symptoms, the decreased performance following esophageal capsaicin exposure highlights the importance of designing sensory interventions based upon neurophysiology and the mechanisms underlying disordered feeding. This mechanistic approach requires comprehensive data collection across the entirety of the feeding process, which can be achieved using models such as the infant pig. NEW & NOTEWORTHY: Simulated gastroesophageal reflux (GER) in an infant pig model resulted in significant changes in pharyngeal swallowing, which suggests that esophageal afferents are centrally integrated to alter motor outputs to the pharynx. In addition, decreased swallow frequency and increased bolus sizes may be underlying mechanisms by which esophageal pathologies induce oropharyngeal dysphagia. The infant pig model used here allows for a mechanistic approach, which can facilitate the design of intervention strategies based on neurophysiology. [ABSTRACT FROM AUTHOR]

The latent reservoir remains a major roadblock to curing human immunodeficiency virus (HIV) infection. Currently available antiretroviral therapy (ART) can suppress active HIV replication, reduce viral loads to undetectable levels, and halt disease progression. However, antiretroviral drugs are unable to target cells that are latently infected with HIV, which can seed viral rebound if ART is stopped. Consequently, a major focus of the field is to study the latent viral reservoir and develop safe and effective methods to eliminate it. Here, we provide an overview of the major mechanisms governing the establishment and maintenance of HIV latency, the key challenges posed by latent reservoirs, small animal models utilized to study HIV latency, and contemporary cure approaches. We also discuss ongoing efforts to apply these approaches in combination, with the goal of achieving a safe, effective, and scalable cure for HIV that can be extended to the tens of millions of people with HIV worldwide. [ABSTRACT FROM AUTHOR]

Favipiravir is a ribonucleoside analogue that has been explored as a therapeutic for the treatment of Ebola Virus Disease (EVD). Promising data from rodent models has informed nonhuman primate trials, as well as evaluation in patients during the 2013–2016 West African EVD outbreak of favipiravir treatment. However, mixed results from these studies hindered regulatory approval of favipiravir for the indication of EVD. This study examined the influence of route of administration, duration of treatment, and treatment schedule of favipiravir in immune competent mouse and guinea pig models using rodent-adapted Zaire ebolavirus (EBOV). A dose of 300 mg/kg/day of favipiravir with an 8-day treatment was found to be fully effective at preventing lethal EVD-like disease in BALB/c mice regardless of route of administration (oral, intraperitoneal, or subcutaneous) or whether it was provided as a once-daily dose or a twice-daily split dose. Preclinical data generated in guinea pigs demonstrates that an 8-day treatment of 300 mg/kg/day of favipiravir reduces mortality following EBOV challenge regardless of route of treatment or duration of treatments for 8, 11, or 15 days. This work supports the future translational development of favipiravir as an EVD therapeutic. [ABSTRACT FROM AUTHOR]

Aim: Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow obstruction and development of emphysema. Among the comorbidities associated with COPD, skeletal muscle dysfunction is known to affect exercise capacity and the survival rate of patients. Pulmonary rehabilitation (PR), via exercise training, is essential for COPD patients. However, the response to PR is most often moderate. An animal model that recapitulates critical features of chronic human disease and provides access to muscle function should therefore be useful to improve PR benefits. Methods: We used a rat model of induced emphysema based on pulmonary instillations of elastase (ELA) and lipopolysaccharides (LPS). We assessed the long‐term effects of ELA/LPS and the potential effectiveness of endurance training on the skeletal muscle function. In vivo strength of the animals, and ex vivo contractility, endurance, type 1 fiber proportion, fiber cross‐sectional area, and capillarization of both soleus and extensor digitorum longus (EDL) were assessed. Results: An impaired overall muscle strength with decreased force, reduced capillarization, and atrophy of type 1 fiber of EDL was observed in ELA/LPS rats. Soleus was not affected. Endurance training was able to reduce fatigability, and increase type 1 fiber proportion and capillarization of soleus, and improve force, endurance, and capillarization of EDL in control and ELA/LPS rats. Conclusion: Our rat model of induced emphysema, which shares some features with the phenotype present in patients with COPD, could represent a suitable model to study skeletal muscle dysfunction and the effects of exercise training on muscle function in patients. [ABSTRACT FROM AUTHOR]

[Display omitted] • Tri-Tharn-Thip tea (Tri-TTa) showed protective effects against ethanol-induced gastric ulcer in rats. • The gastroprotective effect of Tri-TTa could be partly related to decrease in oxidative stress markers as ROS. • The gastroprotective effect of Tri-TTa could be partly related to increase in antioxidant enzyme levels as CAT, SOD and GSH. Tri-Tharn-Thip, a traditional Thai medicine, is a herbal formula used to promote milk production, wound healing, and gastric ulcer. However, no previous studies have reported its anti-gastric ulcer activity. This study aimed to evaluate the gastroprotective effects of Tri-Tharn-Thip tea (Tri-TTa) and explore its potential mechanisms of action by measuring the levels of reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH), mucin, and inducible nitric oxide synthase (iNOS). For this purpose, 24 Wistars rats were divided into four groups. Group I, sham group, received distilled water; Group II, vehicle control group, received distilled water; Group III, positive control group, received omeprazole (20 mg/kg/d); and Group IV, Tri-TTa group, received Tri-TTa (500 mg/kg/d). The treatment protocol lasted 7 d, and all groups except for the sham group received 80 % ethanol on the last day, 4 h before scarification. The gastric tissue was removed; the ulcer area, ulcer score, and pH values were evaluated; and a histopathological examination of the gastric tissue was conducted. ROS, MDA, iNOS, SOD, CAT, and GSH levels were determined using ELISA. Pretreatment with 500 mg/kg Tri-TTa significantly reduced the gastric ulcer area and ROS, MDA, and iNOS levels in rats with ethanol-induced gastric ulcers. Tri-TTa increased the levels of SOD, CAT, and GSH in gastric tissues. Tri-TTa administration also significantly increased mucin content. Tri-TTa exhibited gastroprotective properties that could be linked to decreased oxidative stress markers and elevated antioxidant enzyme levels. [ABSTRACT FROM AUTHOR]

Johne's disease (JD) is an infectious enteric disease in ruminants, causing substantial economic loss annually worldwide. This work aimed to estimate JD's genetic parameters and the phenotypic and genetic trends by incorporating recent data. It also explores the feasibility of a national genetic evaluation for JD susceptibility in Holstein cattle in the United States. The data were extracted from a JD data repository, maintained at the Council on Dairy Cattle Breeding, and initially supplied by 2 dairy record processing centers. The data comprised 365,980 Holstein cows from 1,048 herds participating in a voluntary control program for JD. Two protocol kits, IDEXX Paratuberculosis Screening Ab Test (IDX) and Parachek 2 (PCK), were used to analyze milk samples with the ELISA technique. Test results from the first 5 parities were considered. An animal was considered infected if it had at least one positive outcome. The overall average of JD incidence was 4.72% in these US Holstein cattle. Genotypes of 78,964 SNP markers were used for 25,000 animals randomly selected from the phenotyped population. Variance components and genetic parameters were estimated based on 3 models, namely, a pedigree-only threshold model (THR), a single-step threshold model (ssTHR), and a single-step linear model (ssLR). The posterior heritability estimates of JD susceptibility were low to moderate: 0.11 to 0.16 based on the 2 threshold models and 0.05 to 0.09 based on the linear model. The average reliability of EBVs of JD susceptibility using single-step analysis for animals with or without phenotypes varied from 0.18 (THR) to 0.22 (ssLR) for IDX and from 0.14 (THR) to 0.18 (ssTHR and ssLR) for PCK. Despite no prior direct genetic selection against JD, the estimated genetic trends of JD susceptibility were negative and highly significant. The correlations of bulls' PTA with economically important traits such as milk yield, milk protein, milk fat, somatic cell score, and mastitis were low, indicating a nonoverlapping genetic selection process with traits in current genetic evaluations. Our results suggest the feasibility of reducing the JD incidence rate by incorporating it into the national genetic evaluation programs. [ABSTRACT FROM AUTHOR]

Background: Kawasaki disease (KD) is a syndrome primarily affecting young children, typically under the age of five, and is characterized by the development of acute vasculitis. Through extensive research conducted on both murine and human subjects, it has been demonstrated that heightened levels of reactive oxygen species (ROS) play a pivotal role in the development of KD, especial coronary artery lesions (CALs). Hydrogen gas exhibits potent antioxidant properties that effectively regulate ROS production and the inflammatory response. Methods: We used Lactobacillus casei cell wall extract (LCWE)-induced vasculitis in mice as an animal model of KD and treated the mice with hydrogen gas inhalation. Results: We observed significant dilatation and higher Z scores in the left coronary artery (LCA) in D21 and D28 in mice after LCWE treatment compared to the control group (p < 0.001) and a significant resolution of LCA diameters (p < 0.01) and Z scores (p < 0.01) after treatment with inhaled hydrogen gas. We further demonstrated that serum IL-6 expression was higher in mice after LCWE treatment (p < 0.01) and IL-6 significantly decreased after inhaled hydrogen gas therapy (p < 0.001). Conclusion: According to our literature review, this is the first report where hydrogen gas inhalation has been demonstrated to be effective for the treatment of coronary artery dilatation in a KD murine model. [ABSTRACT FROM AUTHOR]

The use of electrospun fibers as anti-inflammatory drug carriers is currently one of the most interesting approaches for the design of drug delivery systems. In recent years, biodegradable polymers blended with naturally derived ones have been extensively studied to fabricate bioinspired platforms capable of driving biological responses by releasing selected molecular/pharmaceutical signals. Here, sodium diclofenac (DicNa)-loaded electrospun fibers, consisting of polycaprolactone (PCL) or gelatin-functionalized PCL, were studied to evaluate fibroblasts' in vitro and in vivo response. In vitro studies demonstrated that cell adhesion of L929 cells (≈70%) was not affected by the presence of DicNa after 4 h. Moreover, the initial burst release of the drug from PD and PGD fibers, e.g., 80 and 48%, respectively, after 5 h—combined with its sustained release—did not produce any cytotoxic effect and did not negatively influence the biological activity of the cells. In particular, it was demonstrated that the addition of gelatin concurred to slow down the release mechanism, thus limiting the antiproliferative effect of DicNa, as confirmed by the significant increase in cell viability and collagen deposition after 7 days, with respect to PCL alone. In vivo studies in a rat subcutaneous model also confirmed the ability of DicNa-loaded fibers to moderate the inflammatory/foreign body response independently through the presence of gelatin that played a significant role in supporting the formation of small-caliber vessels after 10 days of implantation. All of these results suggest using bicomponent fibers loaded with DicNa as a valid therapeutic tool capable of supporting the wound healing process and limiting in vivo inflammation and rejection phenomena. [ABSTRACT FROM AUTHOR]

Pulmonary drug delivery offers a minimally invasive and efficient method for treating lung conditions, leveraging the lungs' extensive surface area and blood flow for rapid drug absorption. Nebulized therapies aim to deliver drugs directly to the lung tissue. This study investigates the histological impact of nebulized tocilizumab—a monoclonal antibody targeting IL-6, traditionally administered intravenously for rheumatoid arthritis and severe COVID-19—on a murine model. Thirty BALB/c mice were nebulized with tocilizumab (10 mg, 5 mg, and 2.5 mg) and six controls were nebulized with saline solution. They were euthanized 48 h later, and their organs (lungs, nasal mucosa, and liver) were analyzed by a microscopic histological evaluation. The results indicate that all the mice survived the 48 h post-nebulization period without systemic compromise. The macroscopic examination showed no abnormalities, and the histopathological analysis revealed greater lung vascular changes in the control group than in the nebulized animals, which is attributable to the euthanasia with carbon dioxide. Additionally, increased alveolar macrophages were observed in the nebulized groups compared to controls. No significant histological changes were observed in the liver, indicating the safety of nebulized tocilizumab. In conclusion, these findings suggest the potential of nebulized tocilizumab for treating pulmonary inflammation, warranting further research to establish its efficacy and safety in clinical settings. [ABSTRACT FROM AUTHOR]

Objective: Binge‐eating disorder is an eating disorder characterized by recurrent binge‐eating episodes, during which individuals consume excessive amounts of highly palatable food (HPF) in a short time. This study investigates the intricate relationship between repeated binge‐eating episode and the transcriptional regulation of two key genes, adenosine A2A receptor (A2AAR) and dopamine D2 receptor (D2R), in selected brain regions of rats. Method: Binge‐like eating behavior on HPF was induced through the combination of food restrictions and frustration stress (15 min exposure to HPF without access to it) in female rats, compared to control rats subjected to only restriction or only stress or none of these two conditions. After chronic binge‐eating episodes, nucleic acids were extracted from different brain regions, and gene expression levels were assessed through real‐time quantitative PCR. The methylation pattern on genes' promoters was investigated using pyrosequencing. Results: The analysis revealed A2AAR upregulation in the amygdala and in the ventral tegmental area (VTA), and D2R downregulation in the nucleus accumbens in binge‐eating rats. Concurrently, site‐specific DNA methylation alterations at gene promoters were identified in the VTA for A2AAR and in the amygdala and caudate putamen for D2R. Discussion: The alterations on A2AAR and D2R genes regulation highlight the significance of epigenetic mechanisms in the etiology of binge‐eating behavior, and underscore the potential for targeted therapeutic interventions, to prevent the development of this maladaptive feeding behavior. These findings provide valuable insights for future research in the field of eating disorders. Public Significance: Using an animal model with face, construct, and predictive validity, in which cycles of food restriction and frustration stress evoke binge‐eating behavior, we highlight the significance of epigenetic mechanisms on adenosine A2A receptor (A2AAR) and dopamine D2 receptor (D2R) genes regulation. They could represent new potential targets for the pharmacological management of eating disorders characterized by this maladaptive feeding behavior. [ABSTRACT FROM AUTHOR]

Objective: Test the efficacy of the selective orexin 1 receptor (OX1R) antagonist (SO1RA) nivasorexant in an animal model of binge‐eating disorder (BED) and study its dose–response relationship considering free brain concentrations and calculated OX1R occupancy. Compare nivasorexant's profile to that of other, structurally diverse SO1RAs. Gain understanding of potential changes in orexin‐A (OXA) neuropeptide and deltaFosB (ΔFosB) protein expression possibly underlying the development of the binge‐eating phenotype in the rat model used. Method: Binge‐like eating of highly palatable food (HPF) in rats was induced through priming by intermittent, repeated periods of dieting and access to HPF, followed by an additional challenge with acute stress. Effects of nivasorexant were compared to the SO1RAs ACT‐335827 and IDOR‐1104‐2408. OXA expression in neurons and neuronal fibers as well as ΔFosB and OXA‐ΔFosB co‐expression was studied in relevant brain regions using immuno‐ or immunofluorescent histochemistry. Results: All SO1RAs dose‐dependently reduced binge‐like eating with effect sizes comparable to the positive control topiramate, at unbound drug concentrations selectively blocking brain OX1Rs. Nivasorexant's efficacy was maintained upon chronic dosing and under conditions involving more frequent stress exposure. Priming for binge‐like eating or nivasorexant treatment resulted in only minor changes in OXA or ΔFosB expression in few brain areas. Discussion: Selective OX1R blockade reduced binge‐like eating in rats. Neither ΔFosB nor OXA expression proved to be a useful classifier for their binge‐eating phenotype. The current results formed the basis for a clinical phase II trial in BED, in which nivasorexant was unfortunately not efficacious compared with placebo. Public Significance: Nivasorexant is a new investigational drug for the treatment of binge‐eating disorder (BED). It underwent clinical testing in a phase II proof of concept trial in humans but was not efficacious compared with placebo. The current manuscript investigated the drug's efficacy in reducing binge‐like eating behavior of a highly palatable sweet and fat diet in a rat model of BED, which initially laid the foundation for the clinical trial. [ABSTRACT FROM AUTHOR]

Objective To evaluate differentially expressed genes with correlation of gene body methylation. Methods The lingual carcinogenesis was induced through the delivery of drinking water of 4-nitroquinoline-1- oxide (4NQO) with a density of 50 mg/L. The lingual mucosae specimens were harvested at 0, 12, 28 weeks, which represented normal, pre-cancer, and cancer individually. The microarray and methylated DNA immunoprecipitation sequencing (MeDIP-Seq) were used for the evaluation of gene expression and global DNA methylation in these specimens. The mRNA expression of Ubiquitin carboxyl-terminal hydrolase CYLD was tested with qRT-PCR in human normal and dysplasia mucosa. Results There were no statistical differences in gene body methylation among normal (C), pre-cancer (M), and cancer (E) (mean±sofMeDIP-score were 5.58±14.80, 5.79±13.35, 5.83±17.25 individually, H = 100.75, P > 0.05) There presented 145 differentially expressed genes with positive correlation to gene body methylation changes.The expression of CYLD mRNA was decreased in human dysplasia compared to normal mucosa with downregulation of gene body methylation. Conclusions There are many differentially expressed genes with a positive correlation to gene body methylations. The expression of CYLD is downregulated with the downregulation of gene body methylation in earlier stage during tongue carcinogenesis. [ABSTRACT FROM AUTHOR]

Simple Summary: Attention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder in humans, characterised by inattention, hyperactivity, and impulsivity. Evidence suggests that family dogs can exhibit behaviours similar to symptoms of ADHD seen in humans. While past research mainly used questionnaires to assess ADHD-like behaviours in dogs, we aimed to create a simple behavioural test battery covering key ADHD symptom dimensions: inattention, hyperactivity, and impulsivity. Using our previously validated questionnaire (Dog ADHD and Functionality Rating Scale–DAFRS; 2024) in a study involving 59 dogs, we correlated owner-rated DAFRS scores with behavioural test outcomes to further validate our questionnaire. In a subsample of 38 dogs, we also determined whether there is a difference in how owner- and trainer-rated ADHD scores are linked with the test variables. Our test battery included attention, plush dog, leash, and sit tests, all showing significant correlations with the relevant questionnaire scores in an expected direction. Both owner- and trainer-rated ADHD questionnaire factor scores showed correspondence with the relevant behavioural test variables. Dogs' training status only showed association with the sit test. The test battery proved to be consistent in time; test–retest analyses demonstrated moderate-to-excellent agreement across all tests. Our findings endorse the validity of our questionnaire and behavioural tests, providing valuable tools for assessing inattention, hyperactivity, and impulsivity in dogs. Family dogs exhibit neuropsychological deficits similar to attention-deficit/hyperactivity disorder (ADHD) symptoms in humans. Questionnaire methods have mostly been used to assess ADHD-like behaviours in dogs. In addition to our validated questionnaire (Dog ADHD and Functionality Rating Scale–DAFRS; 2024), we developed a simple behavioural test battery covering the ADHD symptom domains (i.e., inattention, hyperactivity, and impulsivity) in dogs. Our main aim was (i) to provide a final external validation step to the DAFRS by examining its associations with the test variables (N = 59); and (ii) to compare owner- and trainer-rated factor scores' associations with the test variables (n = 38). We developed four tests covering the ADHD symptom domains: the attention test (inattention), the plush dog test (impulsivity), the leash test, and the sit test (hyperactivity). All four behavioural variables correlated with their respective questionnaire scores, i.e., the strongest for hyperactivity, and the least strong for inattention. Both owner- and trainer-rated scores (n = 38) correlated with the relevant test variables in an expected direction. Dogs' training status was linked only to the sit test results. Test–retest analyses (n = 34) indicated moderate-to-excellent agreement across all behavioural variables. Our findings support the validity of our novel human-analogue questionnaire for dogs as the behavioural tests strongly correlate with the relevant questionnaire scores, indicating that the two constructs together can effectively assess inattention, hyperactivity, and impulsivity in dogs. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to evaluate whether thermal implant removal of osseointegrated implants is possible using a diode laser with an specific temperature–time interval. Materials and methods: First, tooth extraction of the first three premolars was performed in the maxilla and mandible on both sides of 10 pig. After 3 months, implants were inserted into the upper and lower jaws of 10 pigs. After 3 more months, osseointegrated implants were heated with a laser device to a temperature of 50 °C for 1 min. After 14 days, the implant stability quotient (ISQ), torque-out values, and bone-to-implant contact (BIC) ratio were assessed using resonance frequency analysis. Results: ISQ values showed no significant differences within each group or between the control and test groups. Furthermore, torque-out and BIC value measurements presented no significant differences between the groups. Conclusions: At 50°C, changes in the BIC values were noticeably smaller; however, these differences were not significant. Future studies should evaluate the same procedures at either a higher temperature or longer intervals. Clinical relevance: With only 50 °C for 1 min, a dental implant will not de-integrate predictably. [ABSTRACT FROM AUTHOR]

Although it has been reported that cellular senescence is important in the pathogenesis of asthma, the differential effects of diesel exhaust particle (DEP)-induced cellular senescence on the development of asthma according to age have not been thoroughly studied. We first confirmed that DEP induced cellular senescence in mouse lungs, and then that DEP-induced cellular senescence followed by intranasal instillation of a low-dose house dust mite (HDM) allergen resulted in murine asthma. Second, we examined age-dependent differential effects using 6-week-old (young) and 18-month-old mice (old), and tested whether the mammalian target of the rapamycin (mTOR) pathway plays an important role in this process. Finally, we performed in vitro experiments using human bronchial epithelial cells (HBEC) originating from young and elderly adults to identify the underlying mechanisms. DEP induced cellular senescence in the airway epithelial cells of young and old mice characterized by increased senescence-associated beta-galactosidase, S100A8/9, and high mobility group box 1 (HMGB1) expressions. DEP-induced cellular senescence with subsequent exposure to a low-dose HDM allergen resulted in asthma in young and old mice. Rapamycin (mTOR pathway inhibitor) administration before DEP instillation significantly attenuated these asthmatic features. In addition, after treatment with a low-dose HDM allergen, S100A9 and HMGB1 over-expressed HBEC originating from young and elderly adults greatly activated co-cultured monocyte-derived dendritic cells (DCs). This study showed that DEP-induced senescence made both young and old mice susceptible to allergic sensitization and resultant asthma development by enhancing DC activation. Public health efforts to reduce DEP exposure are warranted. [Display omitted] [ABSTRACT FROM AUTHOR]

Hypohidrotic ectodermal dysplasia is a developmental defect characterized by sparse or absent hair, missing or malformed teeth and defects in eccrine glands. Loss-of-function variants in the X-chromosomal EDA gene have been reported to cause hypohidrotic ectodermal dysplasia in humans, mice, dogs and cattle. We investigated a male cat exhibiting diffuse truncal alopecia with a completely absent undercoat. The cat lacked several teeth, and the remaining teeth had an abnormal conical shape. Whole-genome sequencing revealed a hemizygous missense variant in the EDA gene, XM_011291781.3:c.1042G>A or XP_011290083.1:p.(Ala348Thr). The predicted amino acid exchange is located in the C-terminal TNF signaling domain of the encoded ectodysplasin. The corresponding missense variant in the human EDA gene, p.Ala349Thr, has been reported as a recurring pathogenic variant in several human patients with X-linked hypohidrotic ectodermal dysplasia. The identified feline variant therefore represents the likely cause of the hypohidrotic ectodermal dysplasia in the investigated cat, and the genetic investigation confirmed the suspected clinical diagnosis. This is the first report of an EDA-related hypohidrotic ectodermal dysplasia in cats. [ABSTRACT FROM AUTHOR]

Background: The meticulous selection of appropriate vaccine adjuvants is crucial for optimizing immune responses. Traditionally, pemphigus vulgaris (PV), an autoimmune disorder, has been modelled using complete Freund's adjuvant (CFA). In this study, we aimed to discern potential variations in immune responses elicited by Toll‐like receptor (TLR) ligands as compared to CFA. Methods: A comprehensive investigation was conducted, comparing the effects of these adjuvants in conjunction with ovalbumin or desmoglein‐3. Flow cytometry was employed to analyse distinct cell subsets, while enzyme‐linked immunosorbent assay quantified antigen‐specific antibodies and cytokine levels. Histological examination of harvested skin tissues and transcriptome analysis of skin lesions were performed to identify differentially expressed genes. Results: TLR ligands demonstrated efficacy in inducing PV‐like symptoms in wild‐type mice, in contrast to CFA. This underscored the substantial impact of the adjuvant on self‐antigen tolerance. Furthermore, we proposed an enhanced method for establishing a PV model through adoptive transfer, substituting CFA with TLR ligands. Our results revealed that in contrast to the perception that CFA being the most potent immunopotentiator reported, CFA promoted regulatory T cells (Treg), follicular regulatory T cells and IL‐10‐producing neutrophils, whereas TLR ligands downregulated CCL17 and IL‐10. This suggested potential implications for the recruitment and activation of Treg subsets. While B cell and CD8+ T cell responses exhibited similarity, CFA induced less activation in dendritic cell subsets. A novel mouse model of PV and systemic comparison of immunostimulatory effects of adjuvants were provided by this study. Conclusions: The systematic comparison of CFA and TLR ligands shed light on the distinctive properties of these adjuvants, presenting innovative mouse models for the investigation of pemphigus. This study significantly contributes to adjuvant research and advances our understanding of PV pathogenesis. Key points/highlights: Immunization with desmoglein 3 and Toll‐like receptor (TLR) ligands effectively induces pemphigus symptoms in wild‐type mice, whereas complete Freund's adjuvant (CFA) fails.TLR ligands heightened the autoreactivity of donor cells in the adoptive transfer pemphigus model.CFA promoted regulatory T cells and IL‐10‐producing neutrophils, whereas TLR ligands downregulated CCL17 and IL‐10, leading to more effective immune responses. [ABSTRACT FROM AUTHOR]

The present study aimed to evaluate the genetic parameters of first parity reproductive traits. Information on 762 reproductive records on Saanen × Beetal (S × B) goats reared for approximately five decades was collected from ICAR‐National Dairy Research Institute, Karnal, Haryana (1973–2020). For genetic analysis, single‐trait and multiple‐trait animal models were used. Gibbs sampler for animal model (GSAM) approach was used for estimating (co)variance components of reproductive traits. Six different single‐trait animal models (with or without maternal and environmental effects) were used and the deviance information criterion (DIC) determined the best model. The least squares mean for age at first service (AFS), age at first kidding (AFK), service period (SP), dry period (DP), gestation length (GL), kidding interval (KI), litter weight (LW), number of kids born (NKB) and number of female kids born (NFKB) in first parity were 526.99 ± 4.86, 662.96 ± 5.03, 219.11 ± 6.25, 109.38 ± 6.00, 150.48 ± 0.27, 356.63 ± 4.80 days, 3.87 ± 0.05 kg, 1.27 ± 0.02 and 0.67 ± 0.03, respectively. Lower heritability estimates for these reproductive traits revealed a sparse scope for genetic improvement. Multivariate analysis using Model 1 was carried out to evaluate the genetic and phenotypic correlation of these nine reproductive traits. The genetic correlation of DP and SP was negatively with LW, NKB and NFKB, which is favourable as reduction in SP and DP can improve these economically important traits through indirect selection. Consistent efforts towards genetic improvement of these goat flock poses a promising future for meat industry owing to high prolificacy and good reproductive potential in this flock. [ABSTRACT FROM AUTHOR]

Gravity in space can have a negative impact on the reproductive system. Given that the reproductive system is one of vitamin D's objectives, this study will use a simulated microgravity model to evaluate its impact on the rat reproductive system. Twenty-two male Wistar rats were allocated into four groups at random. Under microgravity circumstances, the rats were housed in both special and standard cages. Each group was then separated into two subgroups, one of which received vitamin D3 and the other did not. Blood was drawn twice to determine blood levels of vitamin D3, LH, FSH, and testosterone. Rat testes were isolated for histological analysis, as well as a piece of epididymis for sperm count and morphological examination. Microgravity had a detrimental effect on testicular tissue, resulting in lower serum levels of LH and testosterone (p-value < 0.001). Spermatogenesis was largely inhibited under microgravity. During microgravity conditions, however, vitamin D3 had a good effect on testicular structure, and the total number of sperm. Simulated microgravity affects the male reproductive system, compromising testicular morphology, sperm parameters, and hormonal balance. However, this study shows that vitamin D3 supplementation can act as a preventative strategy, minimizing the negative consequences of microgravity. The beneficial effect of vitamin D3 on testicular health and sperm quality implies that it may be useful in protecting male reproductive function in space-related situations. [ABSTRACT FROM AUTHOR]

Animal models of authentic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection require operation in biosafety level 3 (BSL-3) containment. In the present study, we established a mouse model employing a single-cycle infectious virus replicon particle (VRP) system of SARS-CoV-2 that can be safely handled in BSL-2 laboratories. The VRP [ΔS-VRP(G)-Luc] contains a SARS-CoV-2 genome in which the spike gene was replaced by a firefly luciferase (Fluc) reporter gene (Rep-Luci), and incorporates the vesicular stomatitis virus glycoprotein on the surface. Intranasal inoculation of ΔS-VRP(G)-Luc can successfully transduce the Rep-Luci genome into mouse lungs, initiating self-replication of Rep-Luci and, accordingly, inducing acute lung injury mimicking the authentic SARS-CoV-2 pathology. In addition, the reporter Fluc expression can be monitored using a bioluminescence imaging approach, allowing a rapid and convenient determination of viral replication in ΔS-VRP(G)-Luc-infected mouse lungs. Upon treatment with an approved anti-SARS-CoV-2 drug, VV116, the viral replication in infected mouse lungs was significantly reduced, suggesting that the animal model is feasible for antiviral evaluation. In summary, we have developed a BSL-2-compliant mouse model of SARS-CoV-2 infection, providing an advanced approach to study aspects of the viral pathogenesis, viral-host interactions, as well as the efficacy of antiviral therapeutics in the future. IMPORTANCE Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly contagious and pathogenic in humans; thus, research on authentic SARS-CoV-2 has been restricted to biosafety level 3 (BSL-3) laboratories. However, due to the scarcity of BSL-3 facilities and trained personnel, the participation of a broad scientific community in SARS-CoV-2 research had been greatly limited, hindering the advancement of our understanding on the basic virology as well as the urgently necessitated drug development. Previously, our colleagues Jin et al. had generated a SARS-CoV-2 replicon by replacing the essential spike gene in the viral genome with a Fluc reporter (Rep-Luci), which can be safely operated under BSL-2 conditions. By incorporating the Rep-Luci into viral replicon particles carrying vesicular stomatitis virus glycoprotein on their surface, and via intranasal inoculation, we successfully transduced the Rep-Luci into mouse lungs, developing a mouse model mimicking SARS-CoV-2 infection. Our model can serve as a useful platform for SARS-CoV-2 pathological studies and antiviral evaluation under BSL2 containment. [ABSTRACT FROM AUTHOR]

The biomechanical properties of the cornea are important for vision and ocular health. Optical coherence elastography (OCE) has the potential to improve our capacity to measure these properties. This study tested a static compression OCE method utilising a commercially available optical coherence tomography (OCT) device, to estimate the Young's modulus of ex-vivo porcine corneal tissue. Approach: OCT was used to image corneal tissue samples before and during loading by static compression. The compressive force was measured with a piezoresistive force sensor, and tissue deformation was quantified through automated image analysis. Ten ex-vivo porcine corneas were assessed and the corneal thickness was also measured to assess the impact of corneal swelling. An average (standard deviation) Young's modulus of 0.271 (+/- 0.091) MPa was determined across the 10 corneas assessed. There was a mean decrease of 1.78 % in corneal thickness at the end of the compression series. These results showed that there was a moderate association between corneal thickness and the Young's modulus recording (R2 = 0.274). Optical coherence elastography utilising clinical instrumentation, can reliably characterise the mechanical properties of the cornea. These results support the further investigation of the technique for in-vivo measurement of the mechanical properties of the human cornea. [ABSTRACT FROM AUTHOR]

With the increase in life expectancy, aging has emerged as a significant health concern. Due to its various mechanisms of action, cardiometabolic drugs are often repurposed for other indications, including aging. This systematic review analyzed and highlighted the repositioning potential of cardiometabolic drugs to increase lifespan as an aging parameter in animal studies and supplemented by information from current clinical trial registries. Systematic searching in animal studies was performed based on PICO: "animal," "cardiometabolic drug," and "lifespan." All clinical trial registries were also searched from the WHO International Clinical Trial Registry Platform (ICTRP). Analysis of 49 animal trials and 10 clinical trial registries show that various cardiovascular and metabolic drugs have the potential to target lifespan. Metformin, acarbose, and aspirin are the three most studied drugs in animal trials. Aspirin and acarbose are the promising ones, whereas metformin exhibits various results. In clinical trial registries, metformin, omega-3 fatty acid, acarbose, and atorvastatin are currently cardiometabolic drugs that are repurposed to target aging. Published clinical trial results show great potential for omega-3 and metformin in healthspan. Systematic Review Registration: crd.york.ac.uk/prospero/display_record.php?RecordID=457358, identifier: CRD42023457358. [ABSTRACT FROM AUTHOR]

Mithun (Bos frontalis), a domestically raised herbivore, holds significant economic importance for the farming community of Northeast India. This study aimed to elucidate the genetic parameters governing Mithun body weight traits across different ages using data from the sole organized semi-intensive Mithun farm in India. Information was gathered from 110 Mithuns born over a period spanning from 2011 to 2022. Body weight taken at week 1 (W1), 1-month (M1), 3-months (M3), 6-months (M6), 9-months (M9), 12-months (M12), 30-months (M30) and 45-months (M45) were considered for the study. The genetic parameters estimation employed the BLUPF90 suite of programs, incorporating univariate Gibbs sampler animal model with fixed effects; season and period of birth, and sex of the animal. Variance and covariance components, including direct additive genetic effects, were estimated. Heritability estimates for the eight body weight traits ranged from 0.47 ± 0.0050 to 0.50 ± 0.0043, indicating varying genetic influence across growth stages. Results revealed that Mithun herd has a substantial genetic variability for growth traits and therefore there is ample scope to select for a better growth rate. Here, we conclude that Month 12 (M12) and Month 9 (M9) body weights exhibit higher heritability, indicating potential for genetic improvement through selective breeding. [ABSTRACT FROM AUTHOR]

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