Selenium deficiency-induced multiple tissue damage with dysregulation of immune and redox homeostasis in broiler chicks under heat stress

Broiler chicks are fast-growing and susceptible to dietary selenium(Se) deficiency. This study sought to reveal the underlying mechanisms of how Se deficiency induces key organ dysfunctions in broilers. Day-old male chicks(n=6 cages/diet, 6 chicks/cage) were fed with a Se-deficient diet(Se-Def, 0.047 mg Se/kg) or the Se-Def+0.3 mg Se/kg(Control, 0.345 mg Se/kg) for 6weeks. The serum, liver, pancreas, spleen, heart, and pectoral muscle of the broilers were collected at week 6 to assay for Se concentration, histopathology, serum metabolome, and tissue transcriptome. Compared with the Control group, Se deficiency induced growth retardation and histopathological lesions and reduced Se concentration in the five organs. Integrated transcriptomics and metabolomics analysis revealed that dysregulation of immune and redox homeostasis related biological processes and pathways contributed to Se deficiency-induced multiple tissue damage in the broilers. Meanwhile, four metabolites in the serum, daidzein, epinephrine, L-aspartic acid and 5-hydroxyindoleacetic acid, interacted with differentially expressed genes with antioxidative effects and immunity among all the five organs, which contributed to the metabolic diseases induced by Se deficiency. Overall, this study systematically elucidated the underlying molecular mechanisms in the pathogenesis of Se deficiency-related diseases, which provides a better understanding of the significance of Se-mediated heath in animals.

Interplay between mesenchymal stem cells and macrophages:Promoting bone tissue repair

The repair of bone tissue damage is a complex process that is well-orchestrated in time and space,a focus and difficulty in orthopedic treatment.In recent years,the success of mesenchymal stem cells(MSCs)-mediated bone repair in clinical trials of large-area bone defects and bone necrosis has made it a candidate in bone tissue repair engineering and regenerative medicine.MSCs are closely related to macrophages.On one hand,MSCs regulate the immune regulatory function by influencing macrophages proliferation,infiltration,and phenotype polarization,while also affecting the osteoclasts differentiation of macrophages.On the other hand,macrophages activate MSCs and mediate the multilineage differentiation of MSCs by regulating the immune microenvironment.The cross-talk between MSCs and macrophages plays a crucial role in regulating the immune system and in promoting tissue regeneration.Making full use of the relationship between MSCs and macrophages will enhance the efficacy of MSCs therapy in bone tissue repair,and will also provide a reference for further application of MSCs in other diseases.

Effect of Chinese Herbal Medicine for Activating Blood Circulation and Detoxifying on Expression of Inflammatory Reaction and Tissue Damage Related Factors in Experimental Carotid Artery Thrombosis Rats

Objective：To observe the pharmaceutical effect of Chinese drugs for activating blood circulation （Xiongshao Capsule,XSC,芎芍胶囊）and for activating blood circulation and detoxification（Xiongshao Capsule and Huanglian Capsule,XSHLC,黄连胶囊）in terms of the indices of thrombosis,inflammatory reaction and tissue damage related factors in experimental carotid artery thrombosis rats.Methods：Fifty Wistar rats were randomly divided into the sham operation group,the model group,the Simvastatin group（SG）,the activating blood circulation（ABC）group,and the activating blood circulation and detoxifying（ABCD）group,with 10 rats in each group.Simvastatin（1.8 mg/kg）,XSC（0.135 g/kg）and XSHLC（0.135 g/kg）were administered to Simvastatin,ABC and ABCD group by gastrogavage,and an equal volume of normal saline was given to the sham operation group and the model group.After 2 weeks of successive medication,the rats in the model and all drug therapy groups were made into experimental carotid artery thrombosis model.The serum levels of matrix metalloproteinases（MMP-9）,tissue inhibitors to metalloproteinase（TIMP-1）,granule membrane protein-140（GMP-140）,tissue-type plasminogen activator（t-PA）,high-sensitivity C-reactive protein（hs-CRP） and interleukin-6（IL-6）were detected with enzyme-linked immunoassay 24 h later.Results：Compared with the model group,the levels of serum GMP-140,hs-CRP,IL-6 and MMP-9 were significantly decreased,and the level of t-PA was significantly increased in the ABC and ABCD group（P〈0.05）,while the level of serum hs-CRP in ABCD group decreased significantly compared with that in the ABC group（P〈0.05）.Conclusions：Chinese drugs both for activating blood circulation and for activating blood circulation and detoxifying have good effects on regulating indices of thrombosis,inflammatory reaction and tissue damage in experimental carotid artery thrombosis rats.The effect of activating blood circulation and detoxifying drugs on regulating the level of serum hs-CRP is superior to that of activating blood circulation drug alone.

Decreased eggshell strength caused by impairment of uterine calcium transport coincide with higher bone minerals and quality in aged laying hens

Background Deteriorations in eggshell and bone quality are major challenges in aged laying hens.This study compared the differences of eggshell quality,bone parameters and their correlations as well as uterine physiologi-cal characteristics and the bone remodeling processes of hens laying eggs of different eggshell breaking strength to explore the mechanism of eggshell and bone quality reduction and their interaction.A total of 24074-week-old Hy-line Brown laying hens were selected and allocated to a high(HBS,44.83±1.31 N)or low(LBS,24.43±0.57 N)eggshell breaking strength group.Results A decreased thickness,weight and weight ratio of eggshells were observed in the LBS,accompanied with ultrastructural deterioration and total Ca reduction.Bone quality was negatively correlated with eggshell quality,marked with enhanced structures and increased components in the LBS.In the LBS,the mammillary knobs and effective layer grew slowly.At the initiation stage of eggshell calcification,a total of 130 differentially expressed genes(DEGs,122 upregulated and 8 downregulated)were identified in the uterus of hens in the LBS relative to those in the HBS.These DEGs were relevant to apoptosis due to the cellular Ca overload.Higher values of p62 protein level,caspase-8 activity,Bax protein expression and lower values of Bcl protein expression and Bcl/Bax ratio were seen in the LBS.TUNEL assay and hematoxylin-eosin staining showed a significant increase in TUNEL-positive cells and tissue damages in the uterus of the LBS.Although few DEGs were identified at the growth stage,similar uterine tissue damages were also observed in the LBS.The expressions of runt-related transcription factor 2 and osteocal-cin were upregulated in humeri of the LBS.Enlarged diameter and more structural damages of endocortical bones and decreased ash were observed in femurs of the HBS.Conclusion The lower eggshell breaking strength may be attributed to a declined Ca transport due to uterine tissue damages,which could affect eggshell calcification and lead to a weak ultrastructure.Impaired uterine Ca transport may result in reduced femoral bone resorption and increased humeral bone formation to maintain a higher mineral and bone quality in the LBS.

Simulation and Experimental Study of Staple Line Reinforcement Surgery

The aim of this study was to evaluate the effectiveness of BM (basement membrane) and SIS (small intestine submucosa) composite extracellular matrix staple line reinforcement in surgical procedures through finite element modelling simulations and leak-proof performance experiments. The mechanical analyses of soft tissues with and without staple line reinforcement were performed by establishing finite element models of three tissues, namely, stomach, intestine and lungs, under the use scenarios of different anastomosis staple models;and the leak-proof performance of the staple line reinforcement was evaluated by simulating leak-proof experiments of gastric incision margins, intestinal sections, and lung incision margins in vitro. The results showed that the equivalent average stresses of the staple line reinforcement were increased by 20 kPa-68 kPa in gastric and intestinal tissues, and 8 kPa-22 kPa in lung tissues. and that the BM and SIS composite extracellular matrix staple line reinforcement could strengthen the anastomotic structure, and at the same time disperse the high stresses of the anastomosed tissues, which could effectively reduce the postoperative complications such as anastomotic bleeding and anastomotic leakage, and provide a safer and more effective optimized design for surgical mechanical anastomosis. It can effectively reduce postoperative complications such as anastomotic bleeding and anastomotic leakage, and provide a safer and more effective optimized design for surgical mechanical anastomosis.

Efficacy of enhanced extracorporeal counterpulsation combined with atorvastatin in the treatment of cognitive impairment after stroke

BACKGROUND Cerebral apoplexy patients are prone to cognitive impairment,and it is very important to choose appropriate treatment methods to improve their cognitive impairment after stroke.AIM To evaluate the effects of enhanced external counterpulsation(EECP)in con-junction with atorvastatin on cognitive function,neurotransmitter levels,and the repair of brain tissue damage in patients with cognitive impairment due to stroke.METHODS In this retrospective study,data from 60 patients with poststroke cognitive impairment due to stroke who were treated in our hospital from February 2021 to July 2022 were analyzed and divided into a treatment group(n=30)and a control group(n=30)according to the different nursing methods applied.Patients in the treatment group received EECP in addition to atorvastatin,while those in the control group received atorvastatin alone.Mini-Mental State Examination(MMSE),Montreal Cognitive Assessment(MoCA)and activities of daily living(ADL)scale scores were compared between the two groups.Additionally,the two groups were compared in terms of serum acetylcholine(ACh),acetylcholin-esterase(AChE),nitric oxide(NO),endothelin-1(ET-1),β2-microglobulin(β2-MG),glial fibrillary acidic protein(GFAP),and visinin-like protein 1(VILIP-1)in the serum.Blood flow measurements from the anterior cerebral artery(ACA),middle cerebral artery(MCA)and posterior cerebral artery(PCA)were compared between the two groups before and after treatment,and the pulsatility index(PI)and resistance index(RI)of each artery were determined.RESULTS MMSE,MoCA,and ADL scores all improved in both groups following treatment,with the study group showing more improvement than the control group(P<0.05).After treatment,there were statistically significant increases in both ACh and NO levels,whereas decreases occurred in AChE,ET-1,β2-MG,VILIP-1,and GFAP,levels and the PI and RI of the left-ACA,right-ACA,left-MCA,right-MCA,left-PCA,and right-PCA.The study group showed greater gains in all metrics than the control group(P<0.05).CONCLUSION EECP combined with atorvastatin is effective in the treatment of cognitive impairment after stroke and can effectively improve the cognitive function,neurotransmitter levels,and brain tissue damage status of patients.

Local Proinflammatory Effects of Repeated Skin Exposure to Warfarin, An Anticoagulant Rodenticide in Rats

Objective： To evaluate the effects of epicutaneous application of anticoagulant warfarin, by examining the presence of tissue injury and immune/inflammatory activity in exposed skin. Methods： Rats were exposed to warfarin by applying 10 μg of warfarin‐sodium to 10‐12 cm 2 skin （range 0.8‐1 μg per 1 cm 2 ） for 3 consecutive days. Tissue injury was evaluated by lipid peroxidation, histomorphological changes and signs of reparative activity in skin. T cell infiltration and selected aspects of epidermal cell activity were examined as indicators of immune/inflammatory skin response to warfarin application. Results： Repeated warfarin application exerted no effect on skin metabolic viability, but resulted in tissue injury （increased malondialdehyde, MDA, production, evident histo‐morphological changes in epidermis and dermis depicting cell injury and death）. Increased numbers of proliferating cell nuclear antigen （PCNA ＋ ） cells indicated reparative processes in injured skin. Infiltration of CD3 ＋ cells （T lymphocytes） along with the increased production of tumor necrosis factor‐α （TNF‐α） by epidermal cells from warfarin‐treated skin and their co‐stimulatory effect in an in vitro T‐cell activation assay demonstrated immunomodulatory effects of epicutaneous warfarin. Conclusion： Presented data have documented tissue damage associated with immune/ inflammatory activity in skin exposed to warfarin. Observed effects are relevant to immunotoxic potential of this anticoagulant in settings of external exposure.

Immunological aspects of age-related diseases

The proportion of elderly people rises in the developed countries. The increased susceptibility of the elderly to infectious diseases is caused by immune dysfunction, especially T cell functional decline. Age-related hematopoietic stem cells deviate from lymphoid lineage to myeloid lineage. Thymus shrinks early in life, which is followed by the decline of na?ve T cells. T-cell receptor repertoire diversity declines by aging, which is caused by cytomegalovirus-driven T cell clonal expansion. Functional decline of B cell induces antibody affinity declines by aging. Many effector functions including phagocytosis of myeloid cells are down regulated by aging. The studies of aging of myeloid cells have some controversial results. Although M1 macrophages have been shown to be replaced by antiinflammatory(M2) macrophages by advanced age, many human studies showed that pro-inflammatory cytokines are elevated in older human. To solve this discrepancy here we divide age-related pathological changes into two categories. One is an aging of immune cell itself. Second is involvement of immune cells to age-related pathological changes. Cellular senescence and damaged cells in aged tissue recruit pro-inflammatory M1 macrophages, which produce pro-inflammatory cytokines and proceed to agerelated diseases. Underlying biochemical and metabolic studies will open nutritional treatment.

Dynamic microenvironment and multiple damaged tissue regeneration in a de novo and synchronized manner

Regenerative medicine has rapidly developed over the past decade and created new opportunities to repair or replace tissue or organ function lost because of congenital defects,age,diseases,or serious damage(Cheng et al.,2016a;Cheng et al.,2016b).Regenerative medicine strategies include the transplantation of bioactive factors,stem cells,or biomaterials,even the induced regeneration in a de novo,depending on the application(Fu,2014a;Huang and Fu,

Effect of oxidative stress-associated damage to the lung tissue caused by different body mass index in the rat models

Objective To investigate the influence of different diets on serum protein expression levels of 4-hydroxynonenal(4-HNE),thioredoxin(Trx),thioredoxin reductase(TrxR)and the sctivities of Trx and TrxR,and to explore the effect of damage to the lung tissue and the underlying mechanisms of different body mass index caused by different diets in the rat models.Methods

Synchrotron Radiation X-Ray Inducing a Significant Increase in the CD38 Level of Rodent Testes by Generating Oxidative Stress

Synchrotron radiation(SR) X-ray has significant potential for medical applications. However, the mechanisms underlying the effects of SR X-ray on biological tissues remain unclear. Because increasing evidence has indicated critical roles of cluster of differentiation 38(CD38) in various cellular functions and cell survival, in this study we used rodent testes as a model to determine the effects of SR X-ray irradiation on the CD38 level of the testes. We found that SR X-ray irradiation led to a significant increase in the CD38 level of rodent testes one day after the irradiation. In contrast, the SR X-ray irradiation did not produce a significant increase in the CD38 level of the testes from the rats that were administered with the antioxidant N-acetyl cysteine, thus suggesting that oxidative stress plays a significant role in the SR X-ray irradiation-induced increase in the CD38 levels. Our study has also provided evidence suggesting that poly(ADP-ribose) polymerase(PARP) activity is not involved in the SR X-ray irradiation-produced effect on the CD38 levels. Collectively, this study has provided first in vivo evidence indicating that CD38 levels can be increased by ionizing radiation, in which oxidative stress plays an important role. Because oxidative stress occurs in ionizing radiation as well as such diseases as cerebral ischemia and Parkinson's disease, oxidative stress may produce pathological effects by inducing increased CD38 levels.