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Journal of Cellular and Molecular... Jun 2024Exosomes derived from bone marrow-derived mesenchymal stem cells (BMSCs) can alleviate the symptoms of pelvic floor dysfunction (PFD) in rats. However, the potential...
Exosomes derived from bone marrow-derived mesenchymal stem cells (BMSCs) can alleviate the symptoms of pelvic floor dysfunction (PFD) in rats. However, the potential therapeutical effects of exosomes derived from BMSCs treated with tumour necrosis factor (TNF)-α on the symptoms of PFD in rats are unknown. Exosomes extracted from BMSCs treated with or without TNF-α were applied to treat PFD rats. Our findings revealed a significant elevation in interleukin (IL)-6 and TNF-α, and matrix metalloproteinase-2 (MMP2) levels in the vaginal wall tissues of patients with pelvic organ prolapse (POP) compared with the control group. Daily administration of exosomes derived from BMSCs, treated either with or without TNF-α (referred to as Exo and TNF-Exo), resulted in increased void volume and bladder void pressure, along with reduced peak bladder pressure and leak point pressure in PFD rats. Notably, TNF-Exo treatment demonstrated superior efficacy in restoring void volume, bladder void pressure and the mentioned parameters compared with Exo treatment. Importantly, TNF-Exo exhibited greater potency than Exo in restoring the levels of multiple proteins (Elastin, Collagen I, Collagen III, IL-6, TNF-α and MMP2) in the anterior vaginal walls of PFD rats. The application of exosomes derived from TNF-α-treated BMSCs holds promise as a novel therapeutic approach for treating PFD.
Topics: Animals; Exosomes; Mesenchymal Stem Cells; Female; Tumor Necrosis Factor-alpha; Rats; Humans; Pelvic Organ Prolapse; Matrix Metalloproteinase 2; Rats, Sprague-Dawley; Interleukin-6; Pelvic Floor; Disease Models, Animal; Bone Marrow Cells; Vagina; Mesenchymal Stem Cell Transplantation; Pelvic Floor Disorders; Middle Aged
PubMed: 38898783
DOI: 10.1111/jcmm.18451 -
Brain and Behavior Jun 2024Social isolation stress (SIS) is a stressor known to trigger depressive behaviors. Psychiatric disorders are associated with neurobiological changes, such as...
BACKGROUND AND AIM
Social isolation stress (SIS) is a stressor known to trigger depressive behaviors. Psychiatric disorders are associated with neurobiological changes, such as neuroinflammation and an increase in nitric oxide (NO) signaling. Despite the well-established detrimental effects of SIS and the involvement of neuroinflammation and NO in depression, potential management strategies, especially resocialization, remain insufficiently explored. Our aim was to elucidate the effects of resocialization on depressive behaviors in socially isolated mice, with a focus on the possible involvement of neuroinflammation and nitrite in the hippocampus (HIP).
METHODS
We utilized 24 Naval Medical Research Institute male mice, maintained under both social and isolation conditions (SC and IC). After the isolation period, the mice were divided into two groups of eight, including the SIS group and a resocialized group. The SC group was kept without exposure to isolation stress. We conducted the open-field test, forced swimming test, and splash test to evaluate depressive behaviors. Additionally, nitrite levels, as well as the gene expression of interleukin (IL)-1β, tumor necrosis factor (TNF), and toll-like receptor 4 (TLR4) in the HIP, were measured.
RESULTS
The study found that resocialization significantly reduces depressive behaviors in SIS mice. The results suggest that the antidepressive effects of resocialization may be partially due to the modulation of the neuroinflammatory response and nitrite levels in the HIP. This is supported by the observed decrease in hippocampal gene expression of IL-1β, TLR4, and TNF, along with a reduction in nitrite levels following resocialization.
CONCLUSION
These insights could pave the way for new management strategies for depression, emphasizing the potential benefits of social interactions.
Topics: Animals; Social Isolation; Hippocampus; Mice; Male; Stress, Psychological; Depression; Nitrites; Neuroinflammatory Diseases; Behavior, Animal; Interleukin-1beta; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha
PubMed: 38898740
DOI: 10.1002/brb3.3604 -
Medical Science Monitor : International... Jun 2024BACKGROUND Sishen Pills (SSPs) are commonly used to treat diarrhea with kidney-yang deficiency syndrome. Trimethylamine-N-oxide (TMAO) is produced through the metabolism...
BACKGROUND Sishen Pills (SSPs) are commonly used to treat diarrhea with kidney-yang deficiency syndrome. Trimethylamine-N-oxide (TMAO) is produced through the metabolism of gut microbiota and can participate in diarrhea in kidney-yang deficiency syndrome by mediating the "gut-kidney axis" to transmit inflammatory factors. This study combined network pharmacology with animal experiments to explore whether SSPs can treat diarrhea with kidney-yang deficiency syndrome by affecting the interaction between TMAO and gut microbiota. MATERIAL AND METHODS A mouse model of diarrhea with kidney-yang deficiency syndrome was constructed by using adenine and Folium sennae decoction, and SSP decoction was used for treatment. This study utilized network pharmacology to predict the potential mechanisms of SSPs in treating diarrhea with kidney-yang deficiency syndrome. 16S rRNA high-throughput sequencing was used to analyze gut mucosal microbial characteristics. ELISA was used to measure TMAO, NOD-like receptor thermal protein domain associated protein 3 (NLRP3), interleukin-1ß (IL-1ß), and transforming growth factor-ß1 (TGF-ß1) levels. We performed Masson and immunohistochemical (Occludin, ZO-1) staining of kidney and small intestinal tissues. The fluorescein diacetate (FDA) hydrolysis spectrophotometric method was used to assess the microbial activity in contents of the small intestine. RESULTS Network pharmacology analysis revealed that SSPs can modulate 108 target points involved in the development of diarrhea, including IL-1ß and TNF. The experimental results demonstrated that SSP decoction significantly improved the general behavioral profiles of the mice, and also reduced TMAO, NLRP3, IL-1ß, and TGF-ß1 levels (P<0.05). Correlation analysis revealed significant positive correlations between TMAO concentrations and NLRP3, IL-1ß and TGF-ß1 levels (P<0.05). Pathological analysis revealed improvements in renal fibrosis and increased expression of the Occludin and ZO-1 proteins in intestinal tissue. In the SSP group, there was a significant increase in microbial activity (P<0.001). According to the sequencing results, the characteristic bacteria of the SSP and NR groups included Succinatimonas hippei, uncultured Solirubrobacter sp., and Clostridium tyrobutyricum. Furthermore, TMAO, NLRP3, IL-1ß, and TGF-ß1 were significantly positively correlated (P<0.05) with Succinatimonas hippei and Clostridium tyrobutyricum. By modulating Firmicutes, Succinatimonas hippei, and Clostridium tyrobutyricum, SSP decoction lowers TMAO levels to alleviate diarrhea with kidney-yang deficiency syndrome. CONCLUSIONS TMAO likely plays a significant role in the "gut-kidney axis" of diarrhea with kidney-yang deficiency syndrome. By adjusting gut microbiota to reduce the inflammatory response that is transmitted through the "gut-kidney axis" as a result of elevated TMAO levels, SSP decoction can alleviate diarrhea with kidney-yang deficiency syndrome.
Topics: Animals; Yang Deficiency; Gastrointestinal Microbiome; Mice; Diarrhea; Methylamines; Drugs, Chinese Herbal; Kidney; Inflammation; Male; Disease Models, Animal; NLR Family, Pyrin Domain-Containing 3 Protein; Interleukin-1beta; RNA, Ribosomal, 16S; Mice, Inbred C57BL; Intestinal Mucosa
PubMed: 38898640
DOI: 10.12659/MSM.944185 -
Zhen Ci Yan Jiu = Acupuncture Research Jun 2024To observe the effect of heat-reinforcing needling (HRN) on synovial inflammation, hypoxia-inducible factor-1α (HIF-1α) and glycolytic activity in serum and synovial...
OBJECTIVES
To observe the effect of heat-reinforcing needling (HRN) on synovial inflammation, hypoxia-inducible factor-1α (HIF-1α) and glycolytic activity in serum and synovial tissue in rabbits with cold syndrome of rheumatoid arthritis (RA), so as to explore its mechanisms underlying improvement of RA.
METHODS
A total of 32 rabbits were randomly divided into normal, model, inhibitor and HRN groups, with 8 rabbits in each group. The RA with cold syndrome model was induced by injecting ovalbumin dry powder and Freund's complete adjuvant combined with cold freezing. Rabbits in the inhibitor group were intraperitoneally injected with 2-methoxyestradiol (2.5 mg/kg), rabbits in the HRN group were received HRN at bilateral "Zusanli" (ST36) for 30 min. The treatments were conducted once daily for 14 consecutive days. After the interventions, the knee circumference and pain threshold were measured. The contents of nicotinamide adenine dinucleotide phosphoric (NADPH), Hexokinase II (HK2) and 6-phosphofructo-2-kinase/fructose-2, 6-biphosphatase 3 (PFKFB3) in serum of rabbits were detected by ELISA. The pathological morphology of synovial tissue of the knee joints were observed by HE staining. The positive expressions of tumor necrosis factor (TNF-α), interleukin (IL)-1β, IL-6 and IL-17 in synovial tissue of knee joint were detected by immunohistochemistry. The content of lactic acid in synovial tissue of rabbit knee joint was detected by spectrophotometry. The expression levels of HIF-1α, pyruvate kinase 2 (PKM2) and lactate dehydrogenase (LDHA) in synovial tissue of knee joint were detected by Western blot.
RESULTS
After intervention, compared with the normal group, the knee circumference was significantly enlarged (<0.05), the pain threshold was significantly decreased (<0.05);the synovial tissue of knee joints showed significant cell proliferation and inflammatory infiltration, the pathological score was significantly increased (<0.05);positive expressions of TNF-α, IL-1β, IL-6 and IL-17, the content of lactic acid in synovial tissue, the contents of NADPH, HK2 and PFKFB3 in serum, and the protein expression levels of HIF-1α, PKM2 and LDHA in synovial tissue were increased (all <0.05) in the model group. Compared with model group, the circumference of knee joint was significantly decreased (<0.05), the pain threshold was significantly increased (<0.05);in synovial tissue, the pathological score was decreased (<0.05);the positive expressions of TNF-α, IL-1β, IL-6 and IL-17 in synovial tissue were decreased (<0.05), the lactic acid content in synovial tissue was decreased (<0.05);the contents of NADPH, HK2 and PFKFB3 in serum and the protein expression levels of HIF-1α, PKM2 and LDHA in synovial tissue were decreased (<0.05) in inhibitor group and HRN group. Compared with the inhibitor group, the synovial pathological score was significantly increased (<0.05), positive expressions of TNF-α, IL-1β, IL-6 and IL-17, the content of lactic acid in synovial tissue, the contents of NADPH, HK2 and PFKFB3 in serum, and the protein expression levels of HIF-1α, PKM2 and LDHA in synovial tissue were increased (all <0.05) in HRN group.
CONCLUSIONS
HRN can increase the pain threshold, reduce the knee circumference and inhibit the inflammatory response in rabbits with cold syndrome of RA. The possible mechanism is related to the down-regulation of HIF-1α and glycolysis activity.
Topics: Animals; Rabbits; Hypoxia-Inducible Factor 1, alpha Subunit; Glycolysis; Humans; Arthritis, Rheumatoid; Male; Acupuncture Therapy; Female; Tumor Necrosis Factor-alpha; Acupuncture Points; Interleukin-6
PubMed: 38897802
DOI: 10.13702/j.1000-0607.20230487 -
Frontiers in Immunology 2024IL6 signaling plays an important role in triggering labor and IL6 is an established biomarker of intrauterine infection/inflammation (IUI) driven preterm labor (PTL)....
INTRODUCTION
IL6 signaling plays an important role in triggering labor and IL6 is an established biomarker of intrauterine infection/inflammation (IUI) driven preterm labor (PTL). The biology of IL6 during IUI at the maternal-fetal interface was investigated in samples from human subjects and non-human primates (NHP).
METHODS
Pregnant women with histologic chorioamnionitis diagnosed by placenta histology were recruited (n=28 term, n=43 for preterm pregnancies from 26-36 completed weeks of gestation). IUI was induced in Rhesus macaque by intraamniotic injection of lipopolysachharide (LPS, n=23). IL1 signaling was blocked using Anakinra (human IL-1 receptor antagonist, n=13), and Tumor necrosis factor (TNF) signaling was blocked by anti TNF-antibody (Adalimumab n=14). The blockers were given before LPS. All animals including controls (intraamniotic injection of saline n=27), were delivered 16h after LPS/saline exposure at about 80% gestation.
RESULTS
IUI induced a robust expression of mRNAs in the fetal membranes (chorion-amnion-decidua tissue) both in humans (term and preterm) and NHP. The major sources of mRNA expression were the amnion mesenchymal cells (AMC) and decidua stroma cells. Additionally, during IUI in the NHP, (a protease that cleaves membrane bound IL6 receptor (IL6R) to release a soluble form) and mRNA increased in the fetal membranes, and the ratio of IL6 and soluble forms of IL6R, gp130 increased in the amniotic fluid signifying upregulation of IL6 trans-signaling. Both IL1 and TNF blockade suppressed LPS-induced mRNAs in the AMC and variably decreased elements of IL6 trans-signaling.
DISCUSSION
These data suggest that IL1 and TNF blockers may be useful anti-inflammatory agents via suppression of IL6 signaling at the maternal-fetal interface.
Topics: Female; Pregnancy; Humans; Animals; Interleukin-6; Signal Transduction; Macaca mulatta; Tumor Necrosis Factor-alpha; Chorioamnionitis; Lipopolysaccharides; Interleukin-1; Adult; Obstetric Labor, Premature; Inflammation; Interleukin 1 Receptor Antagonist Protein; Placenta
PubMed: 38895127
DOI: 10.3389/fimmu.2024.1416162 -
Nutrients Jun 2024: Dietary quality and the consumption of antioxidant-rich foods have been shown to protect against memory decline. Therefore, this double-blind, randomized,... (Randomized Controlled Trial)
Randomized Controlled Trial
An Examination into the Effects of a Nutraceutical Supplement on Cognition, Stress, Eye Health, and Skin Satisfaction in Adults with Self-Reported Cognitive Complaints: A Randomized, Double-Blind, Placebo-Controlled Trial.
: Dietary quality and the consumption of antioxidant-rich foods have been shown to protect against memory decline. Therefore, this double-blind, randomized, placebo-controlled study aimed to investigate the effects of a nutritional supplement on changes in cognitive performance. : In adults aged 40 to 70 years with subjective memory complaints, participants were randomly allocated to take a supplement containing vitamin E, astaxanthin, and grape juice extract daily for 12 weeks or a matching placebo. The primary outcomes comprised changes in cognitive tasks assessing episodic memory, working memory, and verbal memory. Secondary and exploratory measures included changes in the speed of information processing, attention, and self-report measures of memory, stress, and eye and skin health. Moreover, changes in plasma concentrations of brain-derived neurotrophic factor, malondialdehyde, tumor-necrosis factor-α, and interleukin-6 were measured, along with changes in skin carotenoid concentrations. : Compared to the placebo, nutritional supplementation was associated with larger improvements in one primary outcome measure comprising episodic memory ( = 0.037), but not for working memory ( = 0.418) or verbal learning ( = 0.841). Findings from secondary and exploratory outcomes demonstrated that the nutraceutical intake was associated with larger improvements in the Everyday Memory Questionnaire ( = 0.022), increased plasma brain-derived neurotrophic factor ( = 0.030), decreased plasma malondialdehyde ( = 0.040), and increased skin carotenoid concentrations ( = 0.006). However, there were no group differences in changes in the remaining outcome measures. : Twelve weeks of supplementation with a nutritional supplement was associated with improvements in episodic memory and several biological markers associated with cognitive health. Future research will be essential to extend and validate the current findings.
Topics: Humans; Dietary Supplements; Middle Aged; Double-Blind Method; Male; Female; Cognition; Adult; Aged; Brain-Derived Neurotrophic Factor; Vitamin E; Xanthophylls; Skin; Antioxidants; Interleukin-6; Self Report; Carotenoids; Tumor Necrosis Factor-alpha; Memory, Short-Term; Memory, Episodic; Fruit and Vegetable Juices; Malondialdehyde; Eye
PubMed: 38892705
DOI: 10.3390/nu16111770 -
Nutrients May 2024Dendritic cells (DCs) can initiate immune response through the presenting antigens to naïve T lymphocytes. Esculeoside A (EsA), a spirosolane glycoside, is reported as...
Dendritic cells (DCs) can initiate immune response through the presenting antigens to naïve T lymphocytes. Esculeoside A (EsA), a spirosolane glycoside, is reported as a major component in the ripe fruit of tomato. Little is known about the effect of tomato saponin on mice bone marrow-derived DCs. This study revealed that EsA and its aglycon, esculeogenin A (Esg-A), attenuated the phenotypic and functional maturation of murine DCs stimulated by lipopolysaccharide (LPS). We found that EsA/Esg-A down-regulated the expression of major histocompatibility complex type II molecules and costimulatory molecule CD86 after LPS stimulation. It was also determined that EsA-/Esg-A-treated DCs were poor stimulators of allogeneic T-cell proliferation and exhibited impaired interleukin-12 and TNF-α production. Additionally, EsA/Esg-A was able to inhibit TLR4-related and p-NFκB signaling pathways. This study shows new insights into the immunopharmacology of EsA/Esg-A, and represents a novel approach to controlling DCs for therapeutic application.
Topics: Animals; Dendritic Cells; Toll-Like Receptor 4; Signal Transduction; Solanum lycopersicum; Saponins; Mice; NF-kappa B; Lipopolysaccharides; Mice, Inbred C57BL; Interleukin-12; Cell Proliferation; Mice, Inbred BALB C; T-Lymphocytes; Tumor Necrosis Factor-alpha; Fruit; B7-2 Antigen; Sapogenins
PubMed: 38892635
DOI: 10.3390/nu16111699 -
Nutrients May 2024Recently, many studies have been devoted to discovering nutrients for exercise-like effects. Resistance exercise and the intake of essential amino acids (EAAs) are known... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Recently, many studies have been devoted to discovering nutrients for exercise-like effects. Resistance exercise and the intake of essential amino acids (EAAs) are known to be factors that can affect muscle mass and strength improvement. The purpose of this study was to investigate changes in muscle quality, myokines, and inflammation in response to resistance exercise and EAA supplementation.
METHODS
Thirty-four males volunteered to participate in this study. They were assigned to four groups: (1) placebo (CO), (2) resistance exercise (RE), (3) EAA supplementation, and (4) RE + EAA supplementation. Body composition, muscle quality, myokines, and inflammation were measured at baseline and four weeks after treatment.
RESULTS
Lean body fat had decreased in both RE and RE + EAA groups. Lean body mass had increased in only the RE + EAA group. In all groups except for CO, irisin, myostatin A, and TNF-α levels had decreased. The grip strength of the right hand and trunk flexion peak torque increased in the RE group. The grip strength of the left hand, trunk flexion peak torque, and knee flexion peak torque of the left leg were increased in RE + EAA.
CONCLUSIONS
RE, EAA, and RE + EAA could effectively improve the muscle quality, myokine, and inflammation factors of young adult males. This finding highlights the importance of resistance exercise and amino acid intake.
Topics: Humans; Male; Resistance Training; Young Adult; Muscle, Skeletal; Amino Acids, Essential; Body Composition; Inflammation; Dietary Supplements; Tumor Necrosis Factor-alpha; Adult; Muscle Strength; Hand Strength; Myostatin; Fibronectins; Myokines
PubMed: 38892621
DOI: 10.3390/nu16111688 -
Nutrients May 2024Anorexia nervosa (AN) is a severe eating disorder that predominantly affects females and typically manifests during adolescence. There is increasing evidence that serum...
Anorexia nervosa (AN) is a severe eating disorder that predominantly affects females and typically manifests during adolescence. There is increasing evidence that serum cytokine levels are altered in individuals with AN. Previous research has largely focused on adult patients, assuming a low-grade pro-inflammatory state. The serum levels of the cytokine tumour necrosis factor-alpha (TNF-α), interleukin (IL)-1β, IL-6 and IL-15, which are pro-inflammatory, were examined in 63 female adolescents with AN and 41 age-matched healthy controls (HC). We included three time points (admission, discharge, and 1-year follow-up) and investigated the clinical data to assess whether the gut microbiota was associated with cytokine alterations. Relative to the HC group, serum levels of IL-1β and IL-6 were significantly lower during the acute phase (admission) of AN. IL-1β expression was normalised to control levels after weight recovery. TNF-α levels were not significantly different between the AN and HC groups. IL-15 levels were significantly elevated in patients with AN at all time points. We found associations between cytokines and bodyweight, illness duration, depressive symptoms, and the microbiome. In contrast to most findings for adults, we observed lower levels of the pro-inflammatory cytokines IL-1β and IL-6 in adolescent patients, whereas the level of IL-15 was consistently increased. Thus, the presence of inflammatory dysregulation suggests a varied rather than uniform pro-inflammatory state.
Topics: Humans; Anorexia Nervosa; Female; Adolescent; Cytokines; Gastrointestinal Microbiome; Follow-Up Studies; Patient Discharge; Case-Control Studies; Interleukin-1beta; Tumor Necrosis Factor-alpha; Patient Admission; Interleukin-6
PubMed: 38892530
DOI: 10.3390/nu16111596 -
International Journal of Molecular... May 2024Appendicitis is primarily diagnosed based on intraoperative or histopathological findings, and few studies have explored pre-operative markers of a perforated appendix....
Appendicitis is primarily diagnosed based on intraoperative or histopathological findings, and few studies have explored pre-operative markers of a perforated appendix. This study aimed to identify systemic biomarkers to predict pediatric appendicitis at various time points. The study group comprised pediatric patients with clinically suspected appendicitis between 2016 and 2019. Pre-surgical serum interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), intercellular cell-adhesion molecule-1 (ICAM-1), and endothelial selectin (E-selectin) levels were tested from day 1 to day 3 of the disease course. The biomarker values were analyzed and compared between children with normal appendices and appendicitis and those with perforated appendicitis (PA) and non-perforated appendicitis. Among 226 pediatric patients, 106 had non-perforated appendicitis, 102 had PA, and 18 had normal appendices. The levels of all serum proinflammatory biomarkers were elevated in children with acute appendicitis compared with those in children with normal appendices. In addition, the serum IL-6 and TNF-α levels in children with PA were significantly higher, with an elevation in TNF-α levels from days 1 and 2. In addition, serum IL-6 levels increased significantly from days 2 and 3 (both < 0.05). Serum ICAM-1 and E-selectin levels were elevated in the PA group, with consistently elevated levels within the first three days of admission (all < 0.05). These results indicate that increased serum levels of proinflammatory biomarkers including IL-6, TNF-α, ICAM-1, and E-selectin could be used as parameters in the prediction and early diagnosis of acute appendicitis, especially in children with PA.
Topics: Humans; Appendicitis; Child; Female; Male; Biomarkers; Cytokines; Intercellular Adhesion Molecule-1; Chemokines; Child, Preschool; Interleukin-6; Tumor Necrosis Factor-alpha; E-Selectin; Adolescent; Appendectomy
PubMed: 38892260
DOI: 10.3390/ijms25116076