-
Journal of Orthopaedic Surgery and... Jun 2024Tendon stem/progenitor cell (TSPC) senescence contributes to tendon degeneration and impaired tendon repair, resulting in age-related tendon disorders. Ferroptosis, a...
Platelet-derived exosomes alleviate tendon stem/progenitor cell senescence and ferroptosis by regulating AMPK/Nrf2/GPX4 signaling and improve tendon-bone junction regeneration in rats.
BACKGROUND
Tendon stem/progenitor cell (TSPC) senescence contributes to tendon degeneration and impaired tendon repair, resulting in age-related tendon disorders. Ferroptosis, a unique iron-dependent form of programmed cell death, might participate in the process of senescence. However, whether ferroptosis plays a role in TSPC senescence and tendon regeneration remains unclear. Recent studies reported that Platelet-derived exosomes (PL-Exos) might provide significant advantages in musculoskeletal regeneration and inflammation regulation. The effects and mechanism of PL-Exos on TSPC senescence and tendon regeneration are worthy of further study.
METHODS
Herein, we examined the role of ferroptosis in the pathogenesis of TSPC senescence. PL-Exos were isolated and determined by TEM, particle size analysis, western blot and mass spectrometry identification. We investigated the function and underlying mechanisms of PL-Exos in TSPC senescence and ferroptosis via western blot, real-time quantitative polymerase chain reaction, and immunofluorescence analysis in vitro. Tendon regeneration was evaluated by HE staining, Safranin-O staining, and biomechanical tests in a rotator cuff tear model in rats.
RESULTS
We discovered that ferroptosis was involved in senescent TSPCs. Furthermore, PL-Exos mitigated the aging phenotypes and ferroptosis of TSPCs induced by t-BHP and preserved their proliferation and tenogenic capacity. The in vivo animal results indicated that PL-Exos improved tendon-bone healing properties and mechanical strength. Mechanistically, PL-Exos activated AMPK phosphorylation and the downstream nuclear factor erythroid 2-related factor 2 (Nrf2)/glutathione peroxidase 4 (GPX4) signaling pathway, leading to the suppression of lipid peroxidation. AMPK inhibition or GPX4 inhibition blocked the protective effect of PL-Exos against t-BHP-induced ferroptosis and senescence.
CONCLUSION
In conclusion, ferroptosis might play a crucial role in TSPC aging. AMPK/Nrf2/GPX4 activation by PL-Exos was found to inhibit ferroptosis, consequently leading to the suppression of senescence in TSPCs. Our results provided new theoretical evidence for the potential application of PL-Exos to restrain tendon degeneration and promote tendon regeneration.
Topics: Animals; Ferroptosis; Exosomes; NF-E2-Related Factor 2; Cellular Senescence; Rats; Signal Transduction; Phospholipid Hydroperoxide Glutathione Peroxidase; Regeneration; AMP-Activated Protein Kinases; Stem Cells; Tendons; Male; Blood Platelets; Rats, Sprague-Dawley; Rotator Cuff Injuries; Disease Models, Animal
PubMed: 38943181
DOI: 10.1186/s13018-024-04869-8 -
Scientific Reports Jun 2024Helminth infections lead to an overdispersion of the parasites in humans as well as in animals. We asked whether early immune responses against migrating Ascaris larvae...
Helminth infections lead to an overdispersion of the parasites in humans as well as in animals. We asked whether early immune responses against migrating Ascaris larvae are responsible for the unequal distribution of worms in natural host populations and thus investigated a susceptible versus a resistant mouse strain. In mice, the roundworm larvae develop until the lung stage and thus early anti-Ascaris immune responses against the migrating larvae in the liver and lung can be deciphered. Our data show that susceptible C57BL/6 mice respond to Ascaris larval migration significantly stronger compared to resistant CBA mice and the anti-parasite reactivity is associated with pathology. Increased eosinophil recruitment was detected in the liver and lungs, but also in the spleen and peritoneal cavity of susceptible mice on day 8 post infection compared to resistant mice. In serum, eosinophil peroxidase levels were significantly higher only in the susceptible mice, indicating functional activity of the recruited eosinophils. This effect was associated with an increased IL-5/IL-13 production by innate lymphoid cells and CD4 T cells and a pronounced type 2 macrophage polarization in the lungs of susceptible mice. Furthermore, a comparison of wildtype BALB/c and eosinophil-deficient dblGATA-1 BALB/c mice showed that eosinophils were not essential for the early control of migrating Ascaris larvae. In conclusion, in primary infection, a strong local and systemic type 2 immune response during hepato-tracheal helminth larval migration is associated with pathology rather than protection.
Topics: Animals; Ascariasis; Larva; Mice; Th2 Cells; Mice, Inbred BALB C; Lung; Ascaris; Eosinophils; Mice, Inbred C57BL; Mice, Inbred CBA; Liver; Female
PubMed: 38942904
DOI: 10.1038/s41598-024-65281-0 -
Scientific Reports Jun 2024Preterm born (PTB) infants are at risk for injuries related to oxidative stress. We investigated the association between antioxidant and neurodevelopmental gene...
Preterm born (PTB) infants are at risk for injuries related to oxidative stress. We investigated the association between antioxidant and neurodevelopmental gene polymorphisms and oxidative stress parameters in PTB male young adults and their term-born counterparts at rest and during exercise. Healthy young PTB (N = 22) and full-term (N = 15) males underwent graded exercise tests in normobaric normoxic (FO = 0.21) and hypoxic (FO = 0.13) conditions. CAT rs1001179 was associated with decrease in nitrites in the whole group and in PTB individuals (P = 0.017 and P = 0.043, respectively). GPX1 rs1050450 was associated with decrease in ferric reducing antioxidant power in the whole group and in full-term individuals (P = 0.017 and P = 0.021, respectively). HIF1A rs11549465 was associated with decrease in nitrotyrosine and increase in malondialdehyde (P = 0.022 and P = 0.018, respectively). NOTCH4 rs367398 was associated with increase in advanced oxidation protein products and nitrites (P = 0.002 and P = 0.004, respectively) in hypoxia. In normoxia, NOTCH4 rs367398 was associated with increase in malondialdehyde in the whole group (P = 0.043). BDNF rs6265 was associated with decreased nitrites/nitrates in the whole group and in PTB individuals (P = 0.009 and P = 0.043, respectively). Polymorphisms in investigated genes and PTB might influence oxidative stress response after exercise in normoxic or hypoxic conditions far beyond the neonatal period in young male adults.
Topics: Humans; Oxidative Stress; Male; Hypoxia; Antioxidants; Polymorphism, Single Nucleotide; Young Adult; Infant, Newborn; Glutathione Peroxidase GPX1; Hypoxia-Inducible Factor 1, alpha Subunit; Catalase; Adult; Glutathione Peroxidase; Infant, Premature; Nitrites; Malondialdehyde; Tyrosine; Premature Birth
PubMed: 38942829
DOI: 10.1038/s41598-024-65647-4 -
Methods in Enzymology 2024Vanadium-dependent haloperoxidases (VHPOs) are a unique family of enzymes that utilize vanadate, an aqueous halide ion, and hydrogen peroxide to produce an electrophilic...
Vanadium-dependent haloperoxidases (VHPOs) are a unique family of enzymes that utilize vanadate, an aqueous halide ion, and hydrogen peroxide to produce an electrophilic halogen species that can be incorporated into electron rich organic substrates. This halogen species can react with terpene substrates and trigger halonium-induced cyclization in a manner reminiscent of class II terpene synthases. While not all VHPOs act in this capacity, several notable examples from algal and actinobacterial species have been characterized to catalyze regio- and enantioselective reactions on terpene and meroterpenoid substrates, resulting in complex halogenated cyclic terpenes through the action of single enzyme. In this article, we describe the expression, purification, and chemical assays of NapH4, a difficult to express characterized VHPO that catalyzes the chloronium-induced cyclization of its meroterpenoid substrate.
Topics: Alkyl and Aryl Transferases; Terpenes; Cyclization; Vanadium; Substrate Specificity; Peroxidases; Enzyme Assays
PubMed: 38942514
DOI: 10.1016/bs.mie.2024.03.024 -
Plant Science : An International... Jun 2024Receptor-like kinase (ERECTA, ER) is essential for mediating growth, development, and stress response signaling pathway in plants. In this study, we investigated the...
Receptor-like kinase (ERECTA, ER) is essential for mediating growth, development, and stress response signaling pathway in plants. In this study, we investigated the effect of VvER on anthocyanin synthesis as a regulatory factor in transgenic grape callus in response to chilling stress. Results showed that overexpression of VvER reduced the expression of transcription factors VvMYBA1, VvMYB5b, VvMYC2, and VvWDR1, as well as the structural genes VvCHS, VvCHI, VvDFR, VvLDOX, and VvUFGT, and inhibited the anthocyanins synthesis of grape callus at 25℃. VvER reduced proline content and antioxidant enzymes activities of superoxide dismutase (SOD) and peroxidase (POD), and inhibited the expression of anthocyanin synthesis genes to reduce the cold resistance of grape callus. In transgenic Arabidopsis, overexpression of VvER promoted the elongation of Arabidopsis rosettes and sprigs. Under strong light treatment, VvER inhibited the accumulation of anthocyanins in Arabidopsis; Transient expression in strawberry fruit showed that VvER inhibited the synthesis of anthocyanin in strawberry fruit by inhibiting the expression of FaCHI, FaCHS, FaDFR and FaUFGT under low temperature treatment at 10°C, but not under the normal temperature of 25℃. Using Yeast two-hybrid, we found that VvER interacted with transcription factor proteins including VvMYBA1, VvMYB5b and VvWDR1. Furthermore, VvER led to the repression of VvUFGT promoter activity and decreased the anthocyanin biosynthesis genes expression by downregulation MBW complex activity. Totally, VvER could inhibit anthocyanin biosynthesis and involve in the grape plant susceptible to cold stress for grape cultivation in northern China.
PubMed: 38942388
DOI: 10.1016/j.plantsci.2024.112172 -
Archives of Biochemistry and Biophysics Jun 2024Arsenic, an environmental pollutant and poisonous metalloid, has adverse effects on different body organs, including the kidneys. Betaine is a natural nutrient that has...
Arsenic, an environmental pollutant and poisonous metalloid, has adverse effects on different body organs, including the kidneys. Betaine is a natural nutrient that has many beneficial health effects. This research was conducted to examine the impact of betaine on nephrotoxicity caused by inorganic arsenic (NaAsO) in mice. Mice were separated into following groups: control, NaAsO (50 ppm), NaAsO (50 ppm) + betaine (500 mg/kg), and betaine (500 mg/kg). Mice were received NaAsO via drinking water for 8 consecutive weeks and betaine was given to the animals via gavage once daily in the 7th and 8th weeks of the study. Upon completion of the study, the mice were euthanized and samples of serum and kidney were obtained for further evaluations. Administration of NaAsO increased the levels of blood urea nitrogen and creatinine in the serum. It enhanced the amounts of renal malondialdehyde and decreased the total thiol levels, as well as the activity of antioxidant enzymes (catalase, superoxide dismutase, and glutathione peroxidase). Furthermore, it enhanced the levels of renal inflammatory indicators (tumor necrosis factor-alpha and nitric oxide). Western blot results exhibited an increase in the protein expression of nuclear factor kappa B (NF-κB), and phosphorylated NF-κB in NaAsO-treated mice. Histopathological results also confirmed kidney damage caused by NaAsO. However, treatment with betaine improved NaAsO-related kidney injuries in mice. The results of this work indicated that betaine can attenuate kidney damage caused by NaAsO by inhibiting oxidative stress and inflammation.
PubMed: 38942108
DOI: 10.1016/j.abb.2024.110076 -
Journal of Thermal Biology Jun 2024Heat stress poses a significant challenge to sheep farming in arid and semi-arid regions, impacting growth performance, health, and physiological responses. While sheep...
Effects of dietary curcumin nano-micelles on performance, biological responses, and thermal stress resilience in heat-stressed fattening lambs across varying temperature-humidity index conditions: Implications for climate change.
Heat stress poses a significant challenge to sheep farming in arid and semi-arid regions, impacting growth performance, health, and physiological responses. While sheep have innate mechanisms to manage heat stress, prolonged exposure impairs their performance and health. This study evaluated the influence of varying doses of Curcumin Nano-Micelle (CNM) on heat-stressed fattening lambs in northeastern Iran over three months, examining the relationship between CNM doses and growth performance, feeding behavior, physiological responses, immune function, and antioxidant status. Thirty-two crossbred male lambs were included in a completely randomized design with four treatments and eight replications. The experimental treatments were as follows: 1) CTRL: No dietary inclusion of CNM, (control group); 2) T20: Dietary inclusion of 20 mg of CNM per head per day; 3) T40: Dietary inclusion of 40 mg of CNM per head per day; and 4) T80: Dietary inclusion of 80 mg of CNM per head per day. The results revealed that dietary supplementation with 20 and 40 mg of CNM significantly improved live body weight, weight gain, average daily gain (ADG), and feed conversion ratio (FCR) compared to the control treatment. Regression analysis demonstrated quadratic models between growth performance parameters and the Temperature-Humidity Index (THI), indicating a correlation between CNM doses and the animals' responses to heat stress. Regarding eating behavior, CNM doses of 40 and 80 mg/day significantly reduced eating time while increasing ruminating time. Blood analysis indicated significant reductions in glucose levels across all treatments, with T40 significantly reducing both cholesterol and triglyceride (TG) levels. Additionally, CNM supplementation decreased serum malondialdehyde (MDA) levels and increased superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities, indicating enhanced antioxidant status. Physiological responses were influenced by CNM, notably reducing rectal temperature (RT), skin temperature (ST), respiration rate (RR), while pulse rate (PR) increased across various time intervals, particularly in the T80 group. This study demonstrates that CNM supplementation can enhance performance, physiological responses, and antioxidant status in heat-stressed fattening lambs, highlighting its potential to mitigate heat stress effects in sheep farming.
PubMed: 38941825
DOI: 10.1016/j.jtherbio.2024.103905 -
Talanta Jun 2024In this work, the B, N co-doped carbon dots (B, N-CDs) were synthesized via facile hydrothermal approach with 6-aminopyridine boronic acid as precursor. In addition to...
In this work, the B, N co-doped carbon dots (B, N-CDs) were synthesized via facile hydrothermal approach with 6-aminopyridine boronic acid as precursor. In addition to emitting intense blue luminescence when exposed to ultraviolet light, the prepared B, N-CDs displayed remarkable peroxidase-like activity, which could efficiently catalyze the oxidation of 3, 3', 5, 5' -tetramethylbenzidine (TMB) to blue ox-TMB in the presence of hydrogen peroxide (HO). Furthermore, the fluorescence intensity of B, N-CDs increased gradually upon the addition of HO. Since cholesterol oxidase (ChOx) can catalyze the oxidation of cholesterol to form HO, the as-prepared B, N-CDs was then used as both colorimetric and fluorometric sensors for the detection of cholesterol with detection limit of 0.87 and 2.31 μM, respectively. Finally, the dual-mode approach based on B, N-CDs was effectively utilized for detecting cholesterol levels in serum samples, proving the potential application of B, N-CDs in the field of biological assay.
PubMed: 38941812
DOI: 10.1016/j.talanta.2024.126471 -
Poultry Science Jun 2024The main goal of this study was to evaluate the effect of nutraceuticals vs. in-feed antibiotics on performance, blood lipids, antioxidant capacity, cecal microbiota,...
Nutraceuticals vs. antibiotic growth promoters: differential impacts on performance, meat quality, blood lipids, cecal microbiota, and organ histomorphology of broiler chicken.
The main goal of this study was to evaluate the effect of nutraceuticals vs. in-feed antibiotics on performance, blood lipids, antioxidant capacity, cecal microbiota, and organ histomorphology of broiler chickens. A total of 320 one-day-old male broiler chickens were distributed into 5 treatment groups with 8 replicates each. The control group was fed on a basal diet without any additives (NC); the antibiotic group was fed on a basal diet supplemented with 100 mg kg-1 avilamycin (PC); the algal group was fed on a basal diet supplemented with a mixture of Spirulina platensis and Chlorella vulgaris (1.5 g + 1.5 g/kg feed) (SP+CV); the essential oil group was fed with a basal diet containing 300 mg/kg feed rosemary oil (REO); and the probiotics group (a mixture of 1 × 10 CFU/g Bacillus licheniformis, 1 × 10 CFU/g Enterococcus facieum, 1 × 10 CFU/g Lactobacillus acidophilus, and 2 × 10 CFU /g Saccharomyces cerevisiae) was fed with a basal diet supplemented with 0.05% probiotics (PRO). The experiment lasted for 35 d. A beneficial effect of SP+CV and PRO (P < 0.01) was noticed on final body weight, body weight gain, feed conversion ratio, and breast yield. The dietary supplementation with SP+CV, REO, and PRO increased (P < 0.001) broilers' cecal lactic acid bacteria count compared to the control. Lower cecal Clostridium perfringens and Coliform counts (P < 0.001) were noticed in chickens fed the PC and supplemental diets. Malondialdehyde (MDA) concentration was decreased, while glutathione peroxidase (GPx), superoxide dismutase, and catalase enzymes were increased in the breast and thigh meat (P < 0.001) of broiler chickens fed SP+CV, REO, and PRO diets. Dietary SP+CV, REO, and PRO supplementation decreased (P < 0.001) serum total lipids, cholesterol, triglycerides, low-density lipoprotein, and MDA, but increased serum high-density lipoprotein and GPx compared to PC and NC. No pathological lesions were noticed in the liver, kidney, or breast muscle among broilers. The SP+CV, REO, and PRO groups had greater (P < 0.001) intestinal villi height and crypt depth while lower goblet cell densities (P < 0.01) than the control. The present findings suggest that PRO and SP+CV, followed by REO could be suitable alternatives to in-feed antibiotics for enhancing the performance, health, and meat quality of broiler chickens.
PubMed: 38941788
DOI: 10.1016/j.psj.2024.103971 -
Alternative Therapies in Health and... Jun 2024This study aims to investigate the correlation between breast cancer and autoimmune thyroid diseases.
OBJECTIVE
This study aims to investigate the correlation between breast cancer and autoimmune thyroid diseases.
METHODS
A cross-sectional observational study enrolled 100 breast cancer patients at Zhongshan Hospital of Xiamen University from March 2020 to October 2021. Patients were categorized into benign and malignant groups based on tumor pathology. Additionally, 100 healthy female participants underwent physical examinations at the hospital's outpatient center during the same period as controls. The incidence of autoimmune thyroid diseases was assessed via B-type ultrasound, thyroxine level examination, and biopsy. Statistical analyses explored the relationship between autoimmune thyroid diseases and breast cancer.
RESULTS
The pathological type of the malignant group was more severe than that of the healthy group. Although the levels of triiodothyronine (T3), thyroxine (T4), and free thyroxine (FT4) in the malignant group fell within the normal range, the concentrations of T3 and T4 in the malignant group were significantly lower than those in the benign and healthy groups. Additionally, the levels of FT4 and antibodies (anti-thyroid peroxidase [anti-TPO] and anti-thyroglobulin [anti-TG]) were significantly higher in the malignant group compared to the benign and healthy groups, demonstrating statistical significance (P < .05). Conversely, the concentrations of free triiodothyronine (FT3) and thyroid-stimulating hormone (TSH) in the malignant group showed no statistical significance (P > .05). Furthermore, the levels of T3 and T4 did not correlate with the expression of estrogen receptor (ER) and progesterone receptor (PR) in the study group (P > .05). However, both hormone levels were lower in patients with negative HER-2 expression and those with lymph node metastasis (P > .05).
CONCLUSION
Autoimmune thyroid disease correlates with breast cancer occurrence. Thyroid hormone and autoantibody levels aid clinical monitoring and prognosis. Positive anti-TG and anti-TPO expressions, along with T3, T4, and FT4 alterations, impact patients.
PubMed: 38940788
DOI: No ID Found