Genome-wide detections for runs of homozygosity and selective signatures reveal novel candidate genes under domestication in chickens.

BACKGROUND: Indigenous chickens were developed through a combination of natural and artificial selection; essentially, changes in genomes led to the formation of these modern breeds via admixture events. However, their confusing genetic backgrounds include a genomic footprint regulating complex traits, which is not conducive to modern animal breeding. RESULTS: To better evaluate the candidate regions under domestication in indigenous chickens, we considered both runs of homozygosity (ROHs) and selective signatures in 13 indigenous chickens. The genomes of Silkie feather chickens presented the highest heterozygosity, whereas the highest inbreeding status and ROH number were found in Luhua chickens. Short ROH (< 1 Mb), were the principal type in all chickens. A total of 291 ROH islands were detected, and QTLdb mapping results indicated that body weight and carcass traits were the most important traits. An ROH on chromosome 2 covering VSTM2A gene was detected in 12 populations. Combined analysis with the Tajima's D index revealed that 18 genes (e.g., VSTM2A, BBOX1, and RYR2) were under selection and covered by ROH islands. Transcriptional analysis results showed that RYR2 and BBOX1 were specifically expressed in the heart and muscle tissue, respectively. CONCLUSION: Based on genome-wide scanning for ROH and selective signatures, we evaluated the genomic characteristics and detected significant candidate genes covered by ROH islands and selective signatures. The findings in this study facilitated the understanding of genetic diversity and provided valuable insights for chicken breeding and conservation strategies.

Epidemiology, pathogenesis, immune evasion mechanism and vaccine development of porcine Deltacoronavirus.

Coronaviruses have been identified as pathogens of gastrointestinal and respiratory diseases in humans and various animal species. In recent years, the global spread of new coronaviruses has had profound influences for global public health and economies worldwide. As highly pathogenic zoonotic viruses, coronaviruses have become the focus of current research. Porcine Deltacoronavirus (PDCoV), an enterovirus belonging to the family of coronaviruses, has emerged on a global scale in the past decade and significantly influenced the swine industry. Moreover, PDCoV infects not only pigs but also other species, including humans, chickens and cattles, exhibiting a broad host tropism. This emphasizes the need for in-depth studies on coronaviruses to mitigate their potential threats. In this review, we provided a comprehensive summary of the current studies on PDCoV. We first reviewed the epidemiological investigations on the global prevalence and distribution of PDCoV. Then, we delved into the studies on the pathogenesis of PDCoV to understand the mechanisms how the virus impacts its hosts. Furthermore, we also presented some exploration studies on the immune evasion mechanisms of the virus to enhance the understanding of host-virus interactions. Despite current limitations in vaccine development for PDCoV, we highlighted the inhibitory effects observed with certain substances, which offers a potential direction for future research endeavors. In conclusion, this review summarized the scientific findings in epidemiology, pathogenesis, immune evasion mechanisms and vaccine development of PDCoV. The ongoing exploration of potential vaccine candidates and the insights gained from inhibitory substances have provided a solid foundation for future vaccine development to prevent and control diseases associated with PDCoV.

Bacillus amyloliquefaciens SC06 Relieving Intestinal Inflammation by Modulating Intestinal Stem Cells Proliferation and Differentiation via AhR/STAT3 Pathway in LPS-Challenged Piglets.

Bacillus amyloliquefaciens is a well-accepted probiotic, with many benefits for both humans and animals. The ability of intestinal stem cells (ISCs) to develop into several intestinal epithelial cell types helps accelerate intestinal epithelial regeneration. Limited knowledge exists on how bacteria regulated ISCs proliferation and regeneration. Our study investigated the effects of Bacillus amyloliquefaciens supplementation on ISC proliferation and regeneration and intestinal mucosal barrier functions in piglets exposed to lipopolysaccharide (LPS). Eighteen piglets (male, 21 days old) were randomly split into 3 clusters: CON cluster, LPS cluster, and SC06+LPS cluster. On day 21, 100 µg/kg body weight of LPS was intraperitoneally administered to the SC06+LPS and LPS groups. We found SC06 supplementation maintained the intestinal barrier integrity, enhanced intestinal antioxidant capacity, reduced generation of inflammatory response, and suppressed enterocyte apoptosis against the deleterious effects triggered by LPS. In addition, our research indicated that the SC06 supplementation not only improved the ISC regeneration, but also resulted in upregulation of aryl hydrocarbon receptor (AhR) in LPS-challenge piglets. Further studies showed that SC06 also induced ISC differentiation toward goblet cells and inhibited their differentiation to intestinal absorptive cells and enterocytes. The coculture system of SC06 and ileum organoids revealed that SC06 increased the growth of ISCs and repaired LPS-induced organoid damage through activating the AhR/STAT3 signaling pathway. These findings showed that SC06, possibly through the AhR/STAT3 pathway, accelerated ISC proliferation and promoted epithelial barrier healing, providing a potential clinical treatment for IBD. Our research demonstrated that SC06 is effective in preventing intestinal epithelial damage after pathological injury, restoring intestinal homeostasis, and maintaining intestinal epithelial regeneration.

ApoE4 dysregulation incites depressive symptoms and mitochondrial impairments in mice.

Apolipoprotein E4 (ApoE4) is involved in the stress-response processes and is hypothesized to be a risk factor for depression by means of mitochondrial dysfunction. However, their exact roles and underlying mechanisms are largely unknown. ApoE4 transgenic mice (B6. Cg-ApoEtm1Unc Cdh18Tg( GFAP-APOE i4)1Hol /J) were subjected to stress (lipopolysaccharides, LPS) to elucidate the aetiology of ApoE4-induced depression. LPS treatment significantly aggravated depression-like behaviours, concurrent with neuroinflammation and impaired mitochondrial changes, and melatonin/Urolithin A (UA) + 5-aminoimidazole-4-carboxamide 1-ß-D-ribofuranoside (AICAR) reversed these effects in ApoE4 mice. Concurrently, ApoE4 mice exhibited mitophagy deficits, which could be further exacerbated by LPS stimulation, as demonstrated by reduced Atg5, Beclin-1 and Parkin levels, while PINK1 levels were increased. However, these changes were reversed by melatonin treatment. Additionally, proteomic profiling suggested mitochondria-related signalling and network changes in ApoE4 mice, which may underlie the exaggerated response to LPS. Furthermore, HEK 293T cells transfected with ApoE4 showed mitochondria-associated protein and mitophagy defects, including PGC-1α, TFAM, p-AMPKα, PINK1 and LC3B impairments. Additionally, it aggravates mitochondrial impairment (particularly mitophagy), which can be attenuated by triggering autophagy. Collectively, ApoE4 dysregulation enhanced depressive behaviour upon LPS stimulation.

Bacillus amyloliquefaciens SC06 alleviated intestinal damage induced by inflammatory via modulating intestinal microbiota and intestinal stem cell proliferation and differentiation.

The aim of our research was to investigate the effects of Bacillus amyloliquefaciens SC06 on growth performance, immune status, intestinal stem cells (ISC) proliferation and differentiation, and gut microbiota in weaned piglets. Twelve piglets (male, 21 days old, 6.11 ± 0.12 kg) were randomly allocated to CON and SC06 (1 × 108 cfu/kg to diet) groups. This experiment lasted three weeks. Our results showed that SC06 increased (P < 0.05) growth performance and reduced the diarrhea rate in weaned piglets. In addition, SC06 increased intestinal morphology and interleukin (IL)-10 levels, and decreased (P < 0.01) necrosis factor (TNF-α) levels in jejunum and serum. Moreover, weaning piglets fed SC06 had a better balance of colonic microbiota, with an increase in the abundance of Lactobacillus. Furthermore, SC06 enhanced ISCs proliferation and induced its differentiation to goblet cells via activating wnt/ß-catenin pathway in weaned piglets and intestinal organoid. Taken together, SC06 supplementation improved the growth performance and decreased inflammatory response of piglets by modulating intestinal microbiota, thereby accelerating ISC proliferation and differentiation and promoting epithelial barrier healing.

Gut microbiota-derived 5-hydroxyindoleacetic acid from pumpkin polysaccharides supplementation alleviates colitis via MAPKs-PPARγ/NF-κB inhibition.

Polysaccharides from Pumpkin (Cucurbita moschata Duchesne) (PPs) have many pharmacological activities, including anti-oxidant, immune, and intestinal microbiota regulation. These activities have provided some reminders of its potential therapeutic effect on ulcerative colitis (UC), but this has not yet been confirmed. This study preliminarily confirmed its significant anti-UC activity superior to Salicylazosulfapyridine. The average molecular weight of PPs was 3.10 × 105 Da, and PPs mainly comprised Mannose, Rhamnose, Galacturonic acid, Galactosamine, Glucose, and Xylose with molar ratios of 1.58:3.51:34.54:1.00:3.25:3.02. PPs (50, 100 mg/kg) could significantly resist dextran sodium sulfate induced UC on C57BL/6 mice by improving gut microbiota dysbiosis, such as the changes of relative abundance of Bacteroides, Culturomica, Mucispirillum, Escherichia-Shigella, Alistipes and Helicobacter. PPs also reverse the abnormal inflammatory reaction, including abnormal level changes of TNF-α, IFN-γ, IL-1ß, IL-4, IL-6, IL-10, and IL-18. Metabolomic profiling showed that PPs supplementation resulted in the participation of PPAR and MAPK pathways, as well as the increase of 5-hydroxyindole acetic acid (5-HIAA) level. 5-HIAA also exhibited individual and synergistic anti-UC activities in vivo. Furthermore, combination of PPs and 5-HIAA could also elevate the levels of PPARγ in nuclear and inhibit MAPK/NF-ĸB pathway in the colon. This study revealed that PPs and endogenous metabolite 5-HIAA might be developed to treat UC.

A novel dopamine D2 receptor-NR2B protein complex might contribute to morphine use disorders.

Dopamine receptors can form heteromeric interactions with other receptors, including glutamate receptors, and present a novel pharmacological target because it contribute to dopamine-dysregulated brain disorders such as addiction and other motor-related diseases. In addition, dopamine receptors D2 (D2Rs) and glutamate NMDA receptors subtype-NR2B have been implicated in morphine use disorders; however, the molecular mechanism underlying the heteromeric complex of these two receptors in morphine use disorders is unclear. Herein, we focus on interactions between D2R and NR2B in morphine-induced conditioned place preference (CPP) and hyperlocomotion mice models. We found that the D2R-NR2B complex significantly increases in morphine-induced mice models, accompanied by ERK signaling impairment, implying the complex could contribute to the morphine addiction pathophysiological process. Further, we design a brain-penetrant interfering peptide (TAT-D2-KT), which could disrupt interactions of D2R-NR2B and decrease addictive-like behaviors concurrent to ERK signaling improvement. In summary, our data provided the first evidence for a D2R-NMDAR complex formation in morphine use disorders and its underlying mechanism of ERK signaling, which could present a novel therapeutic target with direct implications for morphine acquisition and relapse treatment.

eIF4E phosphorylation mediated LPS induced depressive-like behaviors via ameliorated neuroinflammation and dendritic loss.

The translational defect has emerged as a common feature of neurological disorders. Studies have suggested that alterations between opposing and balanced synaptic protein synthesis and turnover processes could lead to synaptic abnormalities, followed by depressive symptoms. Further studies link this phenomenon with eIF4E and TrkB/BDNF signaling. However, the interplay between the eIF4E and TrkB/BDNF signaling in the presence of neuroinflammation is yet to be explored. To illuminate the role of eIF4E activities within LPS-induced neuroinflammation and depression symptomology, we applied animal behavioral, biochemical, and pharmacological approaches. In addition, we sought to determine whether eIF4E dysregulated activities correlate with synaptic protein loss via the TrkB/BDNF pathway. Our results showed that LPS administration induced depressive-like behaviors, accompanied by neuroinflammation, reduced spine numbers, and synaptic protein dysregulation. Concurrently, LPS treatment enhanced eIF4E phosphorylation and TrkB/BDNF signaling defects. However, eFT508 treatment rescued the LPS-elicited neuroinflammation and depressive behaviors, as well as altered eIF4E phosphorylation, synaptic protein expression, and TrkB/BDNF signaling. The causal relation of eIF4E with BDNF signaling was further explored with TrkB antagonist K252a, which could reverse the effects of eFT508, validating the interplay between the eIF4E and TrkB/BDNF signaling in regulating depressive behaviors associated with neuroinflammation via synaptic protein translational regulation. In conclusion, our results support the involvement of eIF4E-associated translational dysregulation in synaptic protein loss via TrkB/BDNF signaling, eventually leading to depressiven-like behaviors upon inflammation-linked stress.

Rapamycin Exerts an Antidepressant Effect and Enhances Myelination in the Prefrontal Cortex of Chronic Restraint Stress Mice.

Depressive disorder is a psychiatric condition that is characterized by the core symptoms of anhedonia and learned helplessness. Myelination loss was recently found in the prefrontal cortex (PFC) of patients with depression and animal models, but the mechanism of this loss is unclear. In our previous study, chronic restraint stress (CRS) mice showed depressive-like symptoms. In this study, we found that myelin was reduced in the PFC of CRS mice. We also observed increased mammalian target of rapamycin (mTOR) phosphorylation levels in the PFC. Chronic injections of rapamycin, a mTOR complex inhibitor, prevented depressive behavior as shown by the forced swimming test and sucrose preference test. Rapamycin also increased myelination in the PFC of CRS mice. In summary, we found that CRS enhanced mTOR signaling and reduced myelination in the PFC and that rapamycin could prevent it. Our study provides the etiology of reduced myelin in depressive symptoms and suggests that mTOR signaling could be a target for treating depression or improving myelination deficits in depressive disorders.

D1R-5-HT2AR Uncoupling Reduces Depressive Behaviours via HDAC Signalling.

Dopamine and serotonin signalling are associated with major depressive disorder, which is a prevalent life-threatening illness worldwide. Numerous FDA-approved dopamine/serotonin signalling-modifying drugs are available but are associated with concurrent side effects and limited efficacy. Thus, identifying and targeting their signalling pathway is crucial for improving depression treatment. Here, we determined that serotonin receptor 2A (5-HT2AR) abundantly forms a protein complex with dopamine receptor 1 (D1R) in high abundance via its carboxy-terminus in the brains of mice subjected to various chronic stress paradigms. Furthermore, the D1R/5-HT2AR interaction elicited CREB/ERK/AKT modulation during synaptic regulation. An interfering peptide (TAT-5-HT2AR-SV) agitated the D1R/5-HT2AR interaction and attenuated depressive symptoms accompanied by CREB/ERK molecule costimulation. Interestingly, HDAC antagonism but not TrkB antagonism reversed the antidepressant effect of competitive peptides. These findings revealed a novel D1R/5-HT2AR heteroreceptor complex mechanism in the pathophysiology of depression, and their uncoupling ameliorates depressive-like behaviours through HDAC-, and not BDNF-, dependent mechanisms.

Compound Bacillus alleviates diarrhea by regulating gut microbes, metabolites, and inflammatory responses in pet cats.

BACKGROUND: Pet cats frequently have diarrhea in their daily life. Bacillus has a protective role that has crucial beneficial functions on intestinal homeostasis. The aim of this research was to investigate the effects of the compound Bacillus on the prevention of diarrhea, microbiota and metabolism in pet cats. A total of 20 pet cats (1-2 years old, 3.91 ± 0.92 kg) were randomly divided into two groups and fed with a basal diet (Control group), or a basal diet supplemented with 3 × 109 CFU/kg compound Bacillus (Probiotics group). The experiment lasted 33 days. RESULTS: Results showed that the compound Bacillus significantly reduced the rate of soft stools and diarrhea in pet cats compared with the control group (P < 0.05, n = 10). Meanwhile, compared with the control group, the probiotics group significantly decreased the content of IL-1ß and IL-6 and significantly increased IL-10 (P < 0.05, n = 6) in the serum. In addition, feeding probiotics significantly increased the abundance of p_Patescibacter and g_Plectosphaerella, decreased the abundance of p_Firmicutes, p_Gemmatimonadetes, g_Ruminococcaceae_UCG-005, g_Ascochytahe and g_Saccharomyces in the feces of the pet cats (P < 0.05, n = 6). And it also can significantly increase the content of total SCFAs, acetic acid and butyric acid in the feces (P < 0.05, n = 6). The fecal and serum metabolomics analyses revealed that most fecal and serum compounds were involved in metabolism, particularly in chemical structure transformation maps and amino acid metabolism. Also, eugenitol and methyl sulfate were the most significantly increased serum metabolites, and log2FC were 38.73 and 37.12, respectively. Pearson's correlation analysis showed that changes in serum metabolism and fecal microbiota were closely related to immune factors. There was also a strong correlation between serum metabolites and microbiota composition. CONCLUSIONS: The results of this research highlight the potential of the compound Bacillus as a dietary supplement to alleviate diarrhea in pet cats.

Effects of Dietary Bacillus subtilis HC6 on Growth Performance, Antioxidant Capacity, Immunity, and Intestinal Health in Broilers.

This study aimed to investigate the impact of Bacillus subtilis HC6 on the growth performance, immunity, antioxidant capacity, and intestinal health of broilers. A total of 180 one-day-old white feather broilers were randomly divided into two experimental groups, each comprising six replicates of fifteen chicks from 1 to 50 d of age. The groups were either fed a basal diet (CON) or the same diet supplemented with 5 × 108 cfu/kg of Bacillus subtilis HC6 (BS). Our results indicated that compared with the CON, dietary supplementation with BS increased feed efficiency during d 21-50 and d 1-50 (p < 0.05). Moreover, BS supplementation enhanced antioxidant capacity in the serum and liver, and also decreased the activity of diamine oxidase and the level of endotoxins (p < 0.05). Additionally, BS treatment increased the villi height in the jejunum and ileum, increased the ratio of villus height/crypt depth in the ileum, upregulated the expression of tight junction proteins in the jejunal mucosa, and downregulated the levels of IL-22 and IFN-γ on day 50 (p < 0.05). Principal coordinates analysis yielded clear clustering of two groups; dietary BS increased the relative abundance of Bacteroidales_unclassified (genus) and Olsenella (genus), and decreased the abundance of genera Alistipes on day 50, which identified a strong correlation with FCR, serum differential metabolites, or differential gene expression in the jejunal mucosa by spearman correlation analysis. The PICRUSt2 analysis revealed that supplementation with BS enriched the pathways related to xenobiotics biodegradation and metabolism, carbohydrate metabolism, energy metabolism, signaling molecules and interaction, the digestive system, and transport and catabolism. These results demonstrated that dietary BS increased feed efficiency, antioxidant capacity, and the mRNA expression of pro-inflammatory cytokines in the jejunal mucosa; and decreased the activity of diamine oxidase in serum, which might be attributed to the modulation of community composition and the functions of cecal microbiota in white-feathered broilers.

Lactiplantibacillus plantarum Lac16 Attenuates Enterohemorrhagic Escherichia coli O157:H7 Infection by Inhibiting Virulence Traits and Improving Intestinal Epithelial Barrier Function.

Large-scale use of antimicrobials in agriculture and medicine contributes to antibiotic residues in raw foods, the spread of antimicrobial resistance (AMR) and drug pollution, which seriously threatens human health and imposes significant economic burdens on society, suggesting the need for novel therapeutic options that prevent or control zoonoses. In this study, four probiotics were selected to assess their capability to alleviate pathogen-induced damage. Results showed that a simulated gastrointestinal juice and bile tolerated L. plantarum Lac16 with high lactic acid secretion can significantly inhibit the growth of multiple zoonotic pathogens. Lac16 also significantly inhibited the biofilm formation and mRNA expression of virulence traits (genes related to virulence, toxins, flagella biogenesis and motility, antibiotic resistance, biofilm formation and AI-2 quorum sensing) of enterohemorrhagic E. coli O157:H7 (EHEC). Furthermore, Lac16 and Lac26 significantly protected C. elegans against zoonotic pathogen-induced (EHEC, S. typhimurium, C. perfringens) deaths. Moreover, Lac16 significantly promoted epithelial repair and ameliorated lipopolysaccharide (LPS)-induced intestinal epithelial apoptosis and barrier dysfunction by activating the Wnt/ß-catenin signaling pathway, and markedly reduced LPS-induced inflammatory responses by inhibiting the TLR4/MyD88 signaling pathway. The present results indicate that Lac16 attenuates enterohemorrhagic E. coli infection-induced damage by inhibiting key virulence traits of E. coli, promoting epithelial repair and improving intestinal epithelial barrier function, which may be mediated by the activated Wnt/ß-catenin signaling pathway and the inhibited TLR4/MyD88 signaling pathway of the intestinal epithelium.

Ibrutinib Delays ALS Installation and Increases Survival of SOD1G93A Mice by Modulating PI3K/mTOR/Akt Signaling.

Amyotrophic lateral sclerosis (ALS) is a fatal multisystem degenerative disorder with minimal available therapeutic. However, some recent studies showed promising results of immunological-based treatment. Here, we aimed to evaluate the efficacy of ibrutinib against ALS-associated abnormalities by targeting inflammation and muscular atrophy. Ibrutinib was administrated orally to SOD1 G93A mice from 6 to 19 weeks for prophylactic administration and 13 to 19 weeks for therapeutic administration. Our results demonstrated that ibrutinib treatment significantly delayed ALS-like symptom onset in the SOD1 G93A mice, as shown by improved survival time and reduced behavioral impairments. Ibrutinib treatment significantly reduced muscular atrophy by increasing muscle/body weight and decreasing muscular necrosis. The ibrutinib treatment also considerably reduced pro-inflammatory cytokine production, IBA-1, and GFAP expression, possibly mediated by mTOR/Akt/Pi3k signaling in the medulla, motor cortex and spinal cord of the ALS mice. In conclusion, our study demonstrated that ibrutinib could delay ALS onset, increase survival time, and reduce ALS progression by targeting inflammation and muscular atrophy via mTOR/Akt/PI3K modulation.

Adiponectin deficiency accelerates brain aging via mitochondria-associated neuroinflammation.

BACKGROUND: A wide spectrum of changes occurs in the brain with age, from molecular to morphological aspects, and inflammation accompanied by mitochondria dysfunction is one of the significant factors associated with age. Adiponectin (APN), an essential adipokine in glucose and lipid metabolism, is involved in the aging; however, its role in brain aging has not been adequately explored. Here, we aimed to explore the relationship between APN deficiency and brain aging using multiple biochemical and pharmacological methods to probe APN in humans, KO mice, primary microglia, and BV2 cells. RESULTS: We found that declining APN levels in aged human subjects correlated with dysregulated cytokine levels, while APN KO mice exhibited accelerated aging accompanied by learning and memory deficits, anxiety-like behaviors, neuroinflammation, and immunosenescence. APN-deficient mice displayed aggravated mitochondrial dysfunction and HDAC1 upregulation. In BV2 cells, the APN receptor agonist AdipoRon alleviated the mitochondrial deficits and aging markers induced by rotenone or antimycin A. HDAC1 antagonism by Compound 60 (Cpd 60) improved mitochondrial dysfunction and age-related inflammation, as validated in D-galactose-treated APN KO mice. CONCLUSION: These findings indicate that APN is a critical regulator of brain aging by preventing neuroinflammation associated with mitochondrial impairment via HDAC1 signaling.

Roxadustat (FG-4592) abated lipopolysaccharides-induced depressive-like symptoms via PI3K signaling.

Background: Despite its role in inflammation and the redox system under hypoxia, the effects and molecular mechanisms of hypoxia-inducible factor (HIF) in neuroinflammation-associated depression are poorly explored. Furthermore, Prolyl hydroxylase domain-containing proteins (PHDs) regulate HIF-1; however, whether and how PHDs regulate depressive-like behaviors under Lipopolysaccharides (LPS)-induced stress conditions remain covered. Methods: To highlight the roles and underlying mechanisms of PHDs-HIF-1 in depression, we employed behavioral, pharmacological, and biochemical analyses using the LPS-induced depression model. Results: Lipopolysaccharides treatment induced depressive-like behaviors, as we found, increased immobility and decreased sucrose preference in the mice. Concurrently, we examined increased cytokine levels, HIF-1 expression, mRNA levels of PHD1/PHD2, and neuroinflammation upon LPS administration, which Roxadustat reduced. Furthermore, the PI3K inhibitor wortmannin reversed Roxadustat-induced changes. Additionally, Roxadustat treatment attenuated LPS-induced synaptic impairment and improved spine numbers, ameliorated by wortmannin. Conclusion: Lipopolysaccharides-dysregulates HIF-PHDs signaling may contribute to neuroinflammation-coincides depression via PI3K signaling.

Chronic salmon calcitonin exerts an antidepressant effect via modulating the p38 MAPK signaling pathway.

Depression is a common recurrent psychiatric disorder with a high lifetime prevalence and suicide rate. At present, although several traditional clinical drugs such as fluoxetine and ketamine, are widely used, medications with a high efficiency and reduced side effects are of urgent need. Our group has recently reported that a single administration of salmon calcitonin (sCT) could ameliorate a depressive-like phenotype via the amylin signaling pathway in a mouse model established by chronic restraint stress (CRS). However, the molecular mechanism underlying the antidepressant effect needs to be addressed. In this study, we investigated the antidepressant potential of sCT applied chronically and its underlying mechanism. In addition, using transcriptomics, we found the MAPK signaling pathway was upregulated in the hippocampus of CRS-treated mice. Further phosphorylation levels of ERK/p38/JNK kinases were also enhanced, and sCT treatment was able only to downregulate the phosphorylation level of p38/JNK, with phosphorylated ERK level unaffected. Finally, we found that the antidepressant effect of sCT was blocked by p38 agonists rather than JNK agonists. These results provide a mechanistic explanation of the antidepressant effect of sCT, suggesting its potential for treating the depressive disorder in the clinic.

Porcine endogenous retrovirus: classification, molecular structure, regulation, function, and potential risk in xenotransplantation.

Xenotransplantation with porcine organs has been recognized as a promising solution to alleviate the shortage of organs for human transplantation. Porcine endogenous retrovirus (PERV), whose proviral DNAs are integrated in the genome of all pig breeds, is a main microbiological risk for xenotransplantation. Over the last decades, some advances on PERVs' studies have been achieved. Here, we reviewed the current progress of PERVs including the classification, molecular structure, regulation, function in immune system, and potential risk in xenotransplantation. We also discussed the problem of insufficient study on PERVs as well as the questions need to be answered in the future work.

Bacillus amyloliquefaciens SC06 attenuated high-fat diet induced anxiety-like behavior and social withdrawal of male mice by improving antioxidant capacity, intestinal barrier function and modulating intestinal dysbiosis.

Anxiety-like behavior and social withdrawal induced by obesity and oxidative stress are significant health concerns in contemporary society. Our previously study found that Bacillus amyloliquefaciens SC06 (SC06) decreased the body weight of high-fat diet (HFD)-fed male mice and protected porcine intestinal epithelial cells against oxidative stress. The present study further investigated the effect of SC06 on HFD-induced obesity, anxiety-like behavior and social withdrawal of male mice and explored its mechanism. Results showed that SC06 significantly decreased HFD-induced obesity as evidenced by the decreased body weight, weight of liver and epididymal fat. Meanwhile, SC06 attenuated the anxiety-like behavior of HFD-fed male mice as illustrated by the more exploration time in both the open arms of elevated plus maze and the central area of open field and the reversed their social withdrawal tested in the three-chamber social choice task. SC06 also reduced reactive oxygen species (ROS) concentration and normalized the mitochondrial morphology in the hippocampus. SC06 reduced the systemic inflammation and increased the expression of intestinal tight junctions (ZO-1 and Claudin1). Furthermore, SC06 also altered the microbial diversity and composition, and decreased Firmicutes to Bacteroidetes ratio of HFD-fed male mice. These findings suggest SC06 attenuate HFD-induced anxiety-like behavior and social withdrawal of male mice by attenuating hippocampal oxidation stress, systemic inflammation, dysbiosis and improving intestinal barrier function.