Quality of life is markedly influenced by inflammatory pain, with current therapeutic options frequently necessitating extended treatment periods and resulting in many undesirable side effects. In the present study, a Complete Freund's Adjuvant (CFA)- induced model was employed to examine the therapeutic potential of electroacupuncture (EA) in conjunction with subhypnotic doses of dexmedetomidine (DEX) administered at acupoints for managing inflammatory pain. The experimental design involved 36 healthy male C57BL/6 mice equally divided into six experimental treatments: saline (SAL), CFA, diclofenac sodium standard treatment (ST), DEX, EA and combined DEX-EA, with six mice in each group. Treatments commenced 48h following CFA administration, consisting of four treatment sessions at two-day intervals. Following each treatment session, nociceptive thresholds were evaluated. After the last session, paw tissue samples collected from affected paws were subjected to histopathological and immunohistochemical examination, and RNA seq was performed on spinal cord specimens. Results revealed that the DEX-EA therapy produced significantly higher nociceptive thresholds compared to the CFA, DEX monotherapy, and EA monotherapy (P<0.05). Additionally, inflammatory indices showed significant improvements with the DEX-EA, with decreased levels of CD45, MPO, TNF-alpha, IL-6, and IL-1 beta compared to the CFA, DEX monotherapy, and EA monotherapy (P<0.05). Compared to the CFA, non-significant variations were found in nociceptive thresholds and IL-6 level in the DEX and EA monotherapies; however, a significant decrease was found in the level of CD45, MPO, and IL-1 beta (P<0.05). Transcriptomic data revealed 65 differentially expressed genes (DEGs), demonstrating enhanced expression of genes associated with GABAergic neurotransmission, degradative pathways, and autophagic mechanisms. The findings demonstrate that combining EA with DEX produces synergistic anti-nociceptive and anti-inflammatory effects mediated through spinal cord mechanisms.

Neuropathic pain severely affects patients' quality of life. Limited treatments offer relief but often involve long-term use and side effects. This study aimed to explore the electroacupuncture (EA) and subanesthetic alfaxalone (ALF) combination as a novel therapeutic substitute for the treatment of neuropathic pain in a spared nerve injury (SNI) mouse model. Sixty healthy C57BL/6 male mice were randomized into 5 equal-sized groups: sham (n = 12) group, spared nerve injury (SNI; n = 12) group, SNI-ALF (n = 12), SNI-EA (n = 12), and SNI-EA-ALF (n = 12). The SNI mice received the treatment regimens at 8 days postoperatively once every 2 days for 7 treatments in total. The mechanical and thermal pain thresholds were tested after each treatment. Spinal cord samples were collected after the fourth and seventh treatments for detection of diazepam-binding inhibitor (DBI) and γ-aminobutyrate A1 isoform receptor (GABAA1). Mice in the SNI-EA-ALF group showed a significant increase in mechanical and thermal pain thresholds as compared to those in the SNI-ALF and SNI-EA groups during the treatment period (P < 0.05). A significant increase in GABAA1 expression was observed after the fourth and seventh treatments in the SNI-EA-ALF group compared to the SNI-ALF and SNI-EA groups (P < 0.05). In addition, the DBI expression level was significantly lower in the SNI-ALF-EA group than the SNI, SNI-ALF, and SNI-EA groups (P < 0.05). Our results support the use of EA, combined with ALF, to synergistically relieve pain in preclinical models of NP.

Aiming to enhance disease modeling and drug screening for fatty liver disease, a bovine liver organoid model was developed using R-spondin-1 conditioned medium. Adult stem cells from calf liver were cultured and differentiated into organoids, exhibiting specific liver markers and functions. These organoids, treated by a mixture of oleic acid and palmitic acid, demonstrated significant accumulation of total cholesterol and triglycerides, effectively mimicking the fatty liver condition observed in high-yielding dairy cows during the periparturient period. Treatment with 5 natural compounds (silymarin, gastrodin, cordycepin, curcumin, and polydatin) and a positive control (atorvastatin) showed significantly reduced inflammation and lipid accumulation in the bovine liver organoid. Specifically, anti-inflammatory factors were upregulated, pro-inflammatory factors downregulated, and genes related to lipid synthesis were downregulated. Collectively, the application of organoid technology exhibits its potential in simulating disease mechanisms and evaluating therapeutic interventions, notably reducing the need for live animal experiments. Our study establishes a bovine liver organoid model and validates its effectiveness as a tool for advancing disease research and pharmaceutical development.

Combining decellularized biological scaffolds with PRP can prevent the rapid inactivation of growth factors and achieve their controlled and sustained release during tissue regeneration. Therefore, the purpose of this study was to evaluate the combined effect of decellularized bovine pericardium (dBP) and leukocyte-rich platelet-rich plasma (LR-PRP) on the bone repair in a rabbit femoral defect model. Bovine pericardium was decellularized using the Trypsin-Triton X-SDS protocol and histologically assessed. Unicortical bone defects were surgically created in the femur of rabbits (n = 6) and randomly assigned to three treatment allocations: (1) untreated control, (2) LR-PRP, and (3) LR-PRP + dBP-treated defects. Bone defect healing was evaluated using quantitative computed tomography (CT) and histopathological analyses. The dBP achieved 99.2

ObjectiveTo investigate the role of quercetin-added pancreatic prescription food in regulating metabolic homeostasis in dogs.MethodsThe experimental dogs were divided into a control diet group and a prescription diet group. The control group was fed regular food, while the prescription group was fed pancreatic prescription food (3.9 g of quercetin was added in per 1 kg of food) for 8 weeks. Canine physical examination, complete blood count, and serum biochemical tests were conducted at 0 w, 4 w, and 8 w. Non-targeted metabolomics tests were performed using plasma samples at 0 w and 8 w.ResultsDogs that received a quercetin-added pancreatic diet supplemented with quercetin showed no changes in the body weight, fasting blood glucose, body condition score, the indexes of whole blood program of red blood cells, white blood cells and platelets, and most blood biochemical indexes, but increased lipase levels in plasma at 8 w. Quercetin significant improved in metabolic homeostasis, especially in fatty acid, amino acid, and bile acid metabolism. Untargeted metabolomics analysis revealed that quercetin activates ABC transport and arginine/proline pathways, suggesting potential benefits for pancreatitis in large animals, while maintaining comparable safety parameters.ConclusionsQuercetin-added prescription food enhances fatty acid and amino acid metabolism, demonstrating its potential to promote pancreatic function and sustain metabolic homeostasis.

Neuropathic pain (NP), resulting from nerve damage, is difficult to manage and often requires long-term treatment. However, prolonged use of pain medications can lead to addiction and reduced effectiveness over time. Understanding drug tolerance is essential for developing improved pain management strategies. Dexmedetomidine (DEX) is effective in targeting the α2-adrenergic receptor, providing relief from pain, especially NP. However, its extended use leads to tolerance and hinders its clinical utility. Herein, we investigated tolerance mechanisms and potential applications of this drug in managing NP. Adult C57BL/6 mice (male) were distributed into DEX Dosage Groups (n = 48), DEX Tolerance Model Groups (n = 32), SGK1 Inhibitor GSK650394 Groups (n = 48), and NF-κB Inhibitor PDTC Groups (n = 32) to explore dexmedetomidine's effects on NP and tolerance mechanisms. NP was established via selective ligation of the sciatic nerve branch (SNI), followed by administration of DEX. The results revealed a dose-dependent analgesic effect of DEX, with significant increases in pain thresholds observed compared to the sham group (p < 0.05). Optimal efficacy was found at a dose of 30 μg/kg, indicating its potential as an effective treatment for NP (p < 0.05). However, continuous administration of DEX over 13 days induced analgesic tolerance, evidenced by an initial increase in pain thresholds followed by a gradual decrease (p < 0.05). Despite an initial efficacy in elevating pain thresholds, the analgesic effect of DEX diminished over time, returning to pre-dose levels after 5 days (p < 0.05). Transcriptome sequencing of spinal cord samples from mice receiving multiple DEX injections revealed differential gene expression patterns, notably upregulation of SGK1, NR2A, and NR2B subunits (p < 0.05). Inhibiting SGK1 mitigated DEX-induced tolerance, suggesting its involvement in tolerance development (p < 0.05). Moreover, NF-κB inhibition reversed DEX-induced tolerance and implicated the SGK1-NF-κB pathway in the mediation of analgesic tolerance. To sum up, these findings revealed the molecular mechanism underlying DEX-induced analgesic tolerance in the NP model and offer potential avenues for future therapeutic interventions.

OBJECTIVE:To compare cumulative dissipated energy (CDE) and postoperative complications between modified prechop and stop-chop techniques in dogs with hard cataracts. ANIMALS STUDIED:Seventy-nine dogs with 123 mature cataract eyes were studied for measuring anteroposterior lens diameters, or 149 dogs with 225 hard cataract eyes were treated with prechop phacoemulsification or stop-chop phacoemulsification surgery. PROCEDURES:A species-specific prechopper (3.5-5.0 mm width) was designed based on canine anteroposterior lens diameter (APLD: 7.40 ± 0.99 mm) and anterior chamber depth (ACD: 2.54 ± 0.75 mm). Among 225 eyes (149 dogs), 110 eyes were randomly selected for prechop phacoemulsification with the specific prechopper, and 115 eyes for stop-chop phacoemulsification. Surgical outcomes, including CDE, postoperative aqueous flare and complications, were evaluated. RESULTS:The prechop group demonstrated less mean CDE and postoperative aqueous flare incidence compared to the stop-chop group (53.93 ± 15.29 vs. 78.32 ± 21.32, p < 0.001; 35.14% vs. 58.59%, respectively). The prechop group had fewer overall complications than the stop-chop group (35.2% vs. 56.7%). Vision retention rates at final follow-up (30-1440 days postoperation) were comparable (prechop: 95.7% vs. stop-chop: 92.9%), but glaucoma incidence was lower in the prechop group than in the stop-chop cohort (5 vs. 3 eyes). CDE correlated strongly with complication severity. CONCLUSIONS:The prechop technique with a novel prechopper offers a safer, more efficient alternative for phacoemulsification of canine cataracts, particularly in eyes requiring high energy nuclear fragmentation.

Inflammatory pain, an important form of common pain, negatively influences the quality of life. Pathway-selective optogenetic control is a popular tool in neuronal function research; however, attempts to modulate rodent behavior using pathway-selective optogenetics remain unverified. We developed a methodology for pathway-selective optogenetics in rats, focusing on the delivery of recombinant adeno-associated virus (rAAV) containing channelrhodopsin-2 (ChR2) injected at the “Zusanli” acupoints to the dorsal root ganglia (DRG) and toes, which is a part of the complex neuron network. Optogenetic stimulation of gamma-aminobutyric acid (GABA) projections to the “Zusanli” acupoints delivered several rAAV9-GAD1-ChR2-mcherry particles to the spinal cord horn (SCDH) and DRG and few rAAV9-GAD1-ChR2-mcherry particles to toes, thereby evoking an analgesic effect in complete Freund's adjuvant (CFA) rats similar to those of acupuncture. Furthermore, blue light stimulation (LED) and electroacupuncture (EA) reduced inflammatory pain in CFA rats, as evidenced by the changes in the paw edema, paw withdrawal latency (PWL), and paw withdrawal threshold (PWT) values. Further exploration of the mechanisms underlying this phenomenon revealed that optogenetic stimulation upregulates the decarboxylase-65 (GAD65) and decarboxylase-67 (GAD67) protein levels and downregulates the levels of GABA transporter-1 (GAT1) and GABA transporter-3 (GAT3) to alleviate inflammatory pain. The activation of the p38 mitogen-activated protein kinases (MAPK) and Wnt signal transduction pathways decreased the release of interleukin 6 (IL-6), interleukin 10 (IL-10), and tumor necrosis factor-α (TNFα). These findings indicate that optogenetic stimulation of the “Zusanli” acupoint alleviated inflammatory pain.

IntroductionEnteritis and dysbiosis are the major causes of high morbidity and mortality of juvenile ostriches. Chicory (CC) has been proven to have excellent antioxidant, anti-inflammatory, and antibacterial activities. However, it’s unclear whether CC could improve the survival rate of juvenile ostriches by relieving enteritis and correcting dysbiosis.Materials and methodsSouth African ostrich hatchlings (Struthio camelus domesticus) were fed with and without a CC-supplemented diet, and the body weight gain and mortality were compared over 4 months of age. Fresh fecal samples of clinically healthy ostriches were collected, and 16S DNAs were analyzed. Moreover, ostrich chicks with LPS-induced enteritis were fed with different dosages (0, 20, 40, and 80 mg/kg) of chicoric acid (CA), a major bioactive component of CC, for five consecutive days. The expression levels of tight junction (TJ)-related proteins and inflammatory mediators in the ilea were detected with western blot and immunofluorescence.ResultsThe ostrich chicks fed on the CC-supplemented diet began to increase in weight at the 1st month of age and became remarkably heavier at the fourth month (p < 0.01) compared with those fed on the non-CC-supplemented diet. Additionally, the mortality percentage was lower in the chicks fed on the CC-supplemented diet than those fed on the non-CC-supplemented diet (19% vs. 36%, respectively). The diet with the CC supplementation significantly increased the abundance of Phascolactobacteria (linear discriminant analysis; LDA >4) and Bacteroidota (26.7% vs. 17.7%, respectively) as well as decreased the enrichment of Clostridium (5.0% vs. 9.1%, respectively) in the ostrich ilea compared to the diet without CC. The supplementation of CA at a dose of 80 mg/kg significantly increased the expression level of ZO-1 and claudin-3 (p < 0.0001) and suppressed the levels of IL-1β, IL-6, and TNF-α (p < 0.0001) in ostriches with LPS-induced ileitis.ConclusionOur results substantiate that CC or CA supplementation in a diet could effectively improve growth performance and reduce mortality in juvenile ostriches via modulating the gut microbiota and attenuating enteritis.

Objective:This study evaluates the effect of electro-acupuncture (EA) on visceral hypersensitivity (VH) and the expression of N-methyl-D-aspartate receptor-2B (NMDAR-2B) and glutamate transporter EAAT2 in goats. Methods:Twenty-four goats were divided into four groups: saline, 2, 4, 6-Trinitrobenzenesulfonic acid (TNBS), TNBS + EA, and sham EA. EA was administered at Zusanli (ST36) with 60 Hz and 1-3 mA on specified days. Electromyography (EMG) recorded visceromotor response to colorectal distention (CRD). Spinal cords were collected for immunohistochemistry, western blotting, and RT-PCR. The ileum was examined histologically. Results:The repeated EA administration significantly attenuated VH (P < 0.05) in TNBS-treated goats without similar effects in the sham group. NMDAR-2B expression increased (P < 0.01), and EAAT2 expression decreased (P < 0.01) in the TNBS group compared to saline. EA increased the EAAT2 and decreased the NMDAR-2B expression (P < 0.01) compared to TNBS, with no change in the sham-EA group. Conclusion:EA may alleviate VH by upregulating EAAT2 and downregulating NMDAR-2B in the spinal cord of TNBS-treated goats, indicating its potential for treating chronic visceral pain in gastrointestinal disorders.

Background Existing remedial approaches for relieving neuropathic pain (NPP) are challenging and open the way for alternative therapeutic measures such as electroacupuncture (EA). The mechanism underlying the antinociceptive effects of repeated EA sessions, particularly concerning the regulation of the Adora3 receptor and its associated enzymes, has remained elusive. Methods This study used a mouse model of spared nerve injury (SNI) to explore the cumulative analgesic effects of repeated EA at ST36 (Zusanli) and its impact on Adora3 regulation in the spinal cord dorsal horn (SCDH). Forty-eight male mice underwent SNI surgery for induction of neuropathic pain and were randomly assigned to the SNI, SNI + 2EA, SNI + 4EA, and SNI + 7EA groups. Spinal cord (L4-L6) was sampled for immunofluorescence, adenosine (ADO) detection and for molecular investigations following repeated EA treatment. Results Following spared nerve injury (SNI), there was a significant decrease in mechanical withdrawal thresholds (PWTs) and thermal nociceptive withdrawal latency (TWL) in the ipsilateral hind paw on the third day post-surgery, while the contralateral hind paw PWTs showed no significant changes. On subsequent EA treatments, the SNI + EA groups led to a significant increase in pain thresholds (p < 0.05). Repeated EA sessions in SNI mice upregulated Adenosine A3 (Adora3) and cluster of differentiation-73 (CD73) expression while downregulating adenosine deaminase (ADA) and enhancing neuronal instigation in the SCDH. Colocalization analysis of Neun-treated cells revealed increased Adora3 expression, particularly in the SNI + 7EA group. Conclusions In conclusion, cumulative electroacupuncture treatment reduced neuropathic pain by regulating Adora3 and CD73 expression, inhibiting ADA and most likely increasing neuronal activation in the SCDH. This study offers a promising therapeutic option for managing neuropathic pain, paving the way for further research.

Neuropathic pain (NPP) is a devastating and unbearable painful condition. As prevailing treatment strategies have failed to mitigate its complications, there remains a demand for effective therapies. Electroacupuncture (EA) has proved a potent remedial strategy in NPP management in humans and mammals. However, past studies have investigated the underlying mechanism of the analgesic effects of EA on NPP, focusing primarily on adenosine receptors in peripheral tissues. Herein, we elucidate the role of the adenosine (Adora-3) signaling pathway in mediating pain relief through EA in the central nervous system, which is obscure in the literature and needs exploration. Specific pathogen-free (SPF) male adult mice (C57BL/6 J) were utilized to investigate the effect of EA on adenosine metabolism (CD73, ADA) and its receptor activation (Adora-3), as potential mechanisms to mitigate NPP in the central nervous system. NPP was induced via spared nerve injury (SNI). EA treatment was administered seven times post-SNI surgery, and lumber (L4–L6) spinal cord was collected to determine the molecular expression of mRNA and protein levels. In the spinal cord of mice, following EA application, the expression results revealed that EA upregulated (p < 0.05) Adora-3 and CD73 by inhibiting ADA expression. In addition, EA triggered the release of adenosine (ADO), which modulated the nociceptive responses and enhanced neuronal activation. Meanwhile, the interplay between ADO levels and EA-induced antinociception, using an Adora-3 agonist and antagonist, showed that the Adora-3 agonist IB-MECA significantly increased (p < 0.05) nociceptive thresholds and expression levels. In contrast, the antagonist MRS1523 exacerbated neuropathic pain. Furthermore, an upregulated effect of EA on Adora-3 expression was inferred when the Adora-3 antagonist was administered, and the EA treatment increased the fluorescent intensity of Adora-3 in the spinal cord. Taken together, EA effectively modulates NPP by regulating the Adora-3 signaling pathway under induced pain conditions. These findings enhance our understanding of NPP management and offer potential avenues for innovative therapeutic interventions.

The gut microbiota has a profound effect on immunity and metabolic status of the host, which has increasingly attracted research communities. However, the intrinsic mechanism underlying the interplay among these three aspects remains unclear. Different immune states were established via shaping the population structure of gut microbiota with antibacterial agents. The gut microbiota population structures altered with the subtherapeutic level of antibacterial agents facilitated growth phenotype in both piglets and infant mice. Notably, increased colonization of Prevotella copri was observed in the intestinal microbiota, which shifted the immune balance from a CD4+ T cell-dominated population toward a T helper 2 cell (Th2) phenotype, accompanied by a significant elevation of interleukin-13 (IL-13) levels in the portal vein, which was found to display a strong positive correlation with hepatic insulin-like growth factor-1 (IGF-1) levels. Subsequent investigations unveiled that gut-derived IL-13 stimulated the production of hepatic IGF-1 by activating the IL-13R/Jak2/Stat6 pathway in vitro. The IGF-1 levels were increased in the muscles, leading to an upregulation of and resulted the increased genes associated with related to myofibrillar synthesis and differentiation, which ultimately improving the growth phenotype. Our findings highlight the modification of gut immunity states as a central strategy for increasing anabolism of the host, which has significant implications for addressing human undernutrition/stunting, sarcopenia, obesity and related comorbidities.

BACKGROUND:The purpose of our study was to study the composition and content of the feline plasma metabolome revealing the critical metabolites and metabolic pathways associated with age during growth and development.METHODS:Blood samples were collected from juvenile and adult groups for blood routine tests and serum biochemistry tests. Non-targeted metabolomics analyses of plasma were also performed to investigate changes in metabolites and metabolic pathways.RESULTS:In this study, we found that the red blood cell counts, liver function indexes (albumin and gamma-glutamyl transpeptidase), and the concentration of triglyceride and glucose changed significant with growth and development. The metabolomics results revealed that 1427 metabolites were identified in the plasma of young and adult cats. Most of these metabolites belong to major classes of lipids and lipid-like molecules. The most obvious age-related metabolites include reduced levels of chenodeoxycholate, taurocholate, cholate, and taurochenodeoxycholate but increased levels of L-cysteine and taurocyamine in the adult cat's serum. These metabolites are mainly involved in the primary bile acid biosynthesis pathway, the bile secretion pathway, and the taurine and hypotaurine metabolism pathway.CONCLUSION:This study revealed many age-related metabolite alterations in the feline plasma. These age-varying metabolites, especially in the bile acid biosynthesis and secretion metabolism pathways, indicate that the regulation of these pathways is involved in the growth and development of cats. This study promotes our understanding of the mechanism of feline growth and provides new insights into nutrition and medicine for cats of different ages.

Canine atopic dermatitis (CAD) is a prevalent genetically susceptible inflammatory and pruritic allergic skin condition affecting not only the health of dogs but also the quality of life of their owners. Interleukin-31 (IL-31) and interleukin-31 receptor alpha (IL-31RA) are essential for the development of pruritus in primates and mice. Hence, it is expected that inhibiting IL-31RA will be an effective approach to alleviate pruritus. The purpose of the study was to produce anti-canine IL-31RA polyclonal antibodies (anti-IL-31RA pAbs) and evaluate their efficacy in inhibiting house dust mite (HDM)-evoked pruritic responses. Dogs were immunized with antigens formed by IL-31RA recombinant short peptides coupled to BSA to produce anti-IL-31RA pAbs. The CAD model was developed by using HDM allergen stimulation, and the effects of IL-31RA pAbs on the reduction of pruritus in CAD model dogs were examined. The Canine Atopic Dermatitis Extent and Severity Index (CADESI)-4 and pruritus Visual Analog Scale (pVAS) were utilized to evaluate pruritic responses, and skin tissue samples were collected from the inguinal area for pathological assessment of skin inflammatory cell infiltration. The results showed that anti-IL-31RA pAbs with high titers (1:128,000) and specificity were effectively produced. In the CAD model group, the severity of skin damage, pruritus score, inflammatory cell infiltration and level of inflammatory factors were considerably elevated. Anti-IL-31RA pAbs relieved pruritic behavior and dermatitis in dogs compared to placebo-treated dogs. In conclusion, anti-IL-31RA pAbs effectively suppressed CAD in vivo and are anticipated to be an effective novel treatment for pruritic skin disorders such as CAD.

Introduction:The primo vascular system (PVS), an intensive network structure, has been claimed to be representative of the acupuncture meridian. Here, we explored the role of the PVS in local enteritis and its modification by acupuncture.Methods:Chronic cecitis in rabbits was induced by 2,4,6-trinitro-benzene-sulfonic acid (TNBS). The PVS on the cecum was visualized with trypan blue staining, and collected with the help of microsurgical forceps under an optical stereomicroscope.Results:The increased primo vessels (PVs) and primo nodes (PNs) of the PVS on the surface of the cecum were induced by local inflammation, which was positively correlated with the inflammatory cells in the cecal mucosa. Tandem mass tag (TMT) based proteomic analysis revealed that 110 differentiated proteins of the PVS existed between TNBS-treated and control rabbits; 65 proteins were upregulated, while 45 proteins were downregulated. These proteins were mainly enriched in inflammation- and immunity-related processes, such as inflammatory cell proliferation, antigen presentation, and cell adhesion in the proliferated PVS (data are available via ProteomeXchange with the identifiers PXD034280). Importantly, TNBS-induced cecitis, the proliferated PVS and inflammation response-related proteins (CD40, CD45, HLA-DRA1, LAMP1, JAGN1 and FGL1) in the PVS were alleviated or reversed by repetitive electroacupuncture (EA) stimulations.Conclusion:These results suggest that the proliferated PVS and its active inclusions were related to the inflammatory process, which was modified by EA. Our study provides a new avenue for further exploration of the mechanism by which EA exerts anti-inflammatory effects.

Electroacupuncture (EA) is an efficient treatment for visceral hypersensitivity (VH). However, the mechanism underlying VH remains obscure. This study aimed to examine the effect of EA at Housanli acupoint on PAR2 and PAR4 expression in the periaqueductal gray (PAG), rostral ventromedial medulla (RVM), and spinal cord dorsal horn (SCDH) axes, as well as on expression of the proinflammatory cytokines IL-1β and TNF-α, COX-2 enzyme, c-Fos, and the neuropeptides CGRP and SP in the same areas of the descending pain modulatory system. To induce VH in male goats, a 2,4,6-trinitrobenzene-sulfonic acid (TNBS)–ethanol solution was administered to the ileal wall. The visceromotor response (VMR) and nociceptive response at different colorectal distension pressures were measured to evaluate VH. Goats in the TNBS group displayed significantly increased VMR and nociceptive response scores, and elevated protein and mRNA levels of PAR2 and PAR4 in the descending pain modulatory system compared to those in the control group. EA alleviated VMR and nociceptive responses, decreased the protein and mRNA expression levels of PAR2, and elevated those of PAR4 in the descending pain modulatory system. EA may relieve VH by reducing PAR2 expression and increasing PAR4 expression in the descending pain modulatory system.

Background and aims:The metabolomic profile of a biofluid can be affected by age, and thus provides detailed information about the metabolic alterations in biological processes and reflects the in trinsic rule regulating the growth and developmental processes.Methods:To systemically investigate the characteristics of multiple metabolic profiles associated with canine growth, we analyzed the metabolomics in the plasma and urine samples from 15 young and 15 adult beagle dogs via UHPLC-Q-TOFMS-based metabolomics. Blood routine and serum biochemical analyses were also performed on fasting blood samples.Results:The metabolomics results showed remarkable differences in metabolite fingerprints both in plasma and urine between the young and adult groups. The most obvious age-related metabolite alterations include decreased serumlevels of oxoglutaric acid and essential amino acids and derivatives but increased levels of urine levels of O-acetylserine. These changes primarily involved in amino acid metabolism and bile secretion pathways. We also found that the levels of glutamine were consistently higher in both serum and urine of adults, while N-acetylhistamine and uracil concentrations were much lower in the adult group compared to younger ones.Conclusion:Our study provides a whole metabolic profile of serum and urine characteristics of young and adult canines, identifying several metabolites that were significantly associated with age change, which provides theoretical support for the nutrition-related research and age-related homeostasis maintenance in dogs.

The adverse effects of plastic on adult animal and human health have been receiving increasing attention. However, its potential toxicity to fetuses has not been fully elucidated. Herein, biodistribution of polystyrene (PS) particles was determined after the maternal mice were orally given PS micro- and/or nano-particles with and without surface modifications during gestational days 1 to 17. The results showed that PS microplastics (MPs) and nanoparticles (NPs) mainly emerged in the alimentary tract, brain, uterus, and placenta in maternal mice, and only the latter infiltrated into the fetal thalamus. PS NPs and carboxyl-modified NPs induced differentially expressed genes mainly enriched in oxidative phosphorylation and GABAergic synapse. Maternal administration of PS particles during gestation led to anxiety-like behavior of the progenies and their γ-aminobutyric acid (GABA) reduction in the prefrontal cortex and amygdala at Week 8. N-Acetylcysteine (NAC), an antioxidant, alleviated PS particles-induced oxidative injury in the fetal brain and rescued the anxiety-like behavior of the progenies. Additionally, PS nanoparticles caused excessive ROS and apoptosis in neuronal cell lines, which were prevented by glutathione supplementation. These results suggested that PS particles produced a negative effect on fetuses by inducing oxidative injury and suppressing GABA synthesis in their brain. The findings contribute to estimating the risk for PS particles to human and animal health.

Background and aimsOverweight or obesity is one of the most prevalent health burdens in companion pets and predisposes subjects to multiple comorbidities and reduced longevity. Dietary management and sufficient exercise are effective options for weight loss but challenged by modern lifestyle and calorie control-triggered malnutrition. Therefore, this study aimed to develop a formulated obesity control diet characterized by protein- and fiber-rich diet and supplemented with astaxanthin. We systemically evaluated global influences of the designed weight-loss diet on metabolic homeostasis in an obese beagle model. Materials and methodsBeagles were induced for obesity by a 24-week HFD treatment and then included into weight-loss programs. Briefly, obese beagles were randomly assigned to two groups that were fed with a formulated weight-loss diet or control diet, respectively. Body weight and body condition scoring (BCS) were analyzed biweekly. Computed tomography (CT), nuclear magnetic resonance imaging (MRI) measurements, and blood and adipose tissue biopsies were collected at 0 and 8 weeks. Plasma lipids and adipocyte size were also measured after 8 weeks of weight-loss diet feeding. The global influence of the formulated diet on the whole spectrum of gene panels were examined by adipose RNA assays. ResultsTwenty-four weeks of continuous HFD feeding significantly induced obesity in beagles, as evidenced by increased body weight, BCS, abdominal fat mass, and serum lipid levels. The obese and metabolic condition of the modeled canine were effectively improved by an 8-week weight-loss diet administration. Importantly, we did not observe any side effects during the weight loss duration. Transcriptional analysis of adipose tissues further supported that a weight-loss diet significantly increased energy metabolism-related pathways and decreased lipid synthesis-related pathways. ConclusionThe prescribed weight-loss diet exhibited profound benefits in canine weight management with well safety and palatability. These findings support effective strategies of nutritional management and supplementation approaches for weight control in companion animals.