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BACKGROUND: Yougui Pill is a famous formula of the Chinese traditional medicine, which has good efficacy for lumbar disc herniation due to kidney yang insufficiency. OBJECTIVE: To investigate the potential targets and mechanism of action of Yougui Pill in the treatment of lumbar disc herniation by using network pharmacology and molecular docking technology, and verified by animal experiments. METHODS: (1) Network pharmacological analysis: We obtained the active ingredients and targets of Yougui Pill from TCMSP and other databases, collected genes related to lumbar disc herniation from GeneCards database, and took the intersection of the two for the topological analysis to derive the main active ingredients and core therapeutic targets. Gene ontology function analysis and Kyoto encyclopedia of genes and genomes pathway enrichment analysis were performed using R software. (2) Molecular docking: Autodock and Pymol software were utilized for the prediction of molecular binding energy of TCM active ingredients to core therapeutic targets. (3) Animal experiments: Eighteen Sprague-Dawley rats were randomly divided into a control group, a degeneration group and a Yougui Pill group, with 6 rats in each group. A rat model of intervertebral disc degeneration was prepared by fiber puncture method in the degeneration and Yougui Pill groups. At 2 weeks after modeling, Yougui Pill was given by gavage in the Yougui Pill group, once a day for 2 consecutive weeks. The level of tumor necrosis factor-α in serum was detected by the ELISA method, and morphological changes of the annulus fibrosus and nucleus pulposus cells were observed using hematoxylin-eosin staining. RESULTS AND CONCLUSION: There were 90 active ingredients and 64 targets, and the main active ingredients were found to be quercetin, kaempferol, β-carotene, soybean flavonoid, and 4'-O-methylnyasol. The core targets of Yougui Pill for the treatment of lumbar disc herniation were interleukin 6, tumor necrosis factor-α, AKT1, interleukin 1B, and vascular endothelial growth factor A. Enrichment analysis revealed that the intersecting genes might be expressed through the interleukin-17 signaling pathway, tumor necrosis factor signaling pathway, MAPK signaling pathway, PI3K-AKT signaling pathway, and other signaling pathways to improve intervertebral disc degeneration. The molecular docking test verified that quercetin, kaempferol, and β-carotene had strong binding ability to the core targets. Animal experiments showed that the level of serum tumor necrosis factor α in the degeneration group was higher than that in the control group (P < 0.05), and the level of serum tumor necrosis factor α in the Yougui Pill group was lower than that in the degeneration group (P < 0.05). Hematoxylineosin staining showed that the fibrous annulus of the intervertebral discs and the structure of the nucleus pulposus in the degeneration group were destroyed, and the number of nucleus pulposus cells was reduced; there was a tendency to reconstructing the fibrous annulus of the intervertebral discs in the Yougui Pill group, and the number of nucleus pulposus cells increased compared with the degeneration group. To conclude, Yougui Pill may treat lumbar disc herniation by improving disc degeneration through the effects of quercetin, kaempferol, beta-carotene and other key active ingredients on core targets such as tumor necrosis factor. [ABSTRACT FROM AUTHOR]

BACKGROUND: There is less report about mitigating sustained bone grinding injuries during craniotomy based on a model of traumatic brain injury established using the modified Feeney’s free-fall method. OBJECTIVE: To modify a modified traumatic brain injury model by altering the opening of the skull window. METHODS: Thirty-six Sprague-Dawley rats were equally randomized into sham group, model group and modified model group. The modified procedure of opening the bone window was used in the modified model group. Six to eight small holes of 0.3-0.5 mm in diameter were punched at the edge of the impact area and the drill was immediately withdrawn without touching the cortex. In the modified model group, the skull window was opened by using the modified method, while the skull window in the model group was opened using the conventional method. The modified model group and model group were established using the Feeney’s free-fall method. In the sham group, only the skull window was opened without impact. The modified neurological severity scoring was performed at 1 day after modeling. T2 weighted imaging was performed and T2 values were measured at 1 and 7 days after modeling. Hematoxylin-eosin staining of the brain section was made for histopathological observation at 7 days after modeling. The level of blood viscosity, interleukin-6, interleukin-1β, and tumor necrosis factor-α were determined at 7 days after modeling. RESULTS AND CONCLUSION: Compared with the sham group, the modified neurological severity scores in the model group and modified model group were significantly increased at 1 day after modeling (P < 0.000 1). Meanwhile, the modified neurological severity scores in the modified model group were lower than those in the model group (P < 0.000 1). Compared with the sham group, the T2 values were significantly increased in the model group and modified model group at 1 and 7 days after modeling (P < 0.05), while the T2 values in the modified model group were lower than those in the model group (P < 0.05). Compared with the sham group, the level of blood viscosity, interleukin-6, interleukin-1β and tumor necrosis factor-α were increased in the model group and modified model group at 7 days after modeling (P < 0.05), while the level of interleukin-6 in the modified model group was lower than that in the model group (P < 0.05). To conclude, establishing a modified traumatic brain injury model based on the Feeney’s free-fall method provides better controls of injury factors during cranial opening. [ABSTRACT FROM AUTHOR]

BACKGROUND: Amyotrophic lateral sclerosis is a progressive neurodegenerative disease, which often leads to the death of neurons in the brain and spinal cord. The pathogenesis of amyotrophic lateral sclerosis is extremely complex, with high refractory rate and mortality rate. There are only two kinds of drugs for its treatment, so it is urgent to develop new treatment methods to improve the prognosis of patients. OBJECTIVE: To review the mechanism of Chinese medicine and mesenchymal stem cells regulating the immune response in the treatment of amyotrophic lateral sclerosis. METHODS: “Traditional Chinese medicine, medical stem cells, ALS, immune response” were Chinese and English search terms. Articles were retrieved from WanFang, CNKI, PubMed, Web of Science and other databases from 2010 to 2023. Finally, 69 articles were included for review. RESULTS AND CONCLUSION: (1) The article summarizes in detail the five mechanisms of traditional Chinese medicine regulating the immune response in the treatment of amyotrophic lateral sclerosis: mainly including the promotion of expression of closed zone protein-1 and closed protein-5 by traditional Chinese medicine such as borneol and astragaloside IV to rebuild the integrity of the blood central nervous system barrier. Fufangteng Mixture can regulate the receptor molecules on the surface of the natural killer cells to inhibit their autotoxicity. The complement system factors such as Scutellaria barbata and patchouli can inhibit their abnormal activation. Tripterygium wilfordii and Uncaria rhynchophylla inhibit the activation of microglia by mediating the production of extracellular signal-regulated kinase 1/2 attenuated inducible nitric oxide synthase. Zuogui Pill and Trichosanthes kirilowii Root promote the expression of interleukin-10 and regulate T cells to improve the immune environment. (2) Through existing research, five mechanisms of mesenchymal stem cells regulating the immune response in the treatment of amyotrophic lateral sclerosis have been summarized, mainly including reducing the expression of aquaporin 4 and reducing endothelial nitric oxide synthase signal transduction to repair the integrity of the immune barrier; releasing indoleamine 2,3-dioxygenase, prostaglandin E2 and other factors to resist natural killer cell toxicity; secretion factor H interferes with the activity of invertase and inhibits abnormal activation of the complement system; regulating the CX3CL1/CX3CR1 system axis or secreting transforming growth factors β, which can change the phenotype of microglia and inhibit its activity by other ways; increasing the expression of interleukin-10 or activating the STATS phosphorylation pathway to restore T cell function. (3) At present, there are few studies on the combination of traditional Chinese medicine and mesenchymal stem cells in the treatment of amyotrophic lateral sclerosis. Relevant research reports have shown that Jiweiling Injection can promote stem cell proliferation and differentiation and that Buyang Huanwu decoction combined with bone marrow mesenchymal stem cells can significantly improve the integrity of the blood-brain barrier. In the future, further exploration is needed to explore the synergistic treatment effect of both on refractory amyotrophic lateral sclerosis. [ABSTRACT FROM AUTHOR]

Objective To evaluate the preservation effect of normothermic mechanical perfusion with red blood cells from humanized genetically modified pig on severed human limbs. Methods Severed human limbs were perfused with red blood cells from humanized genetically modified pigs for 6 h. Perfusion solution was taken every hour to measure the oxygen partial pressure, Na+, K+, Ca2+, pH value, glucose, lactic acid and creatine kinase levels. Superficial flexor muscle was sampled to detect the changes of tumor necrosis factor (TNF)-α, interleukin (IL)-2 and IL-1 levels. At 0 and 6 h after perfusion, the superficial flexor muscles of the forearm were taken for pathological examination. Intercellular space and glycogen consumption of skeletal muscles were observed. An appropriate amount of forearm vessels was collected every 2 h to detect the apoptosis of vascular endothelial cells. X-ray angiography was performed before perfusion and 6 h after perfusion to observe the filling degree of finger-tip peripheral vessels. Results The oxygen partial pressure was observed in the normal range throughout the perfusion. Na+ concentration peaked at 1 h, reaching 138.7 mmol/L, and then fluctuated within the normal range. K+ level peaked at 2 h up to 6.08 mmol/L, then decreased and fluctuated within the normal range. Ca2+ concentration reached the peak at 4 h, up to 1.03 mmol/L. Glucose level was gradually decreased at the beginning of perfusion, reaching the lowest value of 17.7 mmol/L at 2h after perfusion, and then maintained a dynamic balance. The pH value was decreased to 7.28 at 6 h after perfusion. The lactic acid level was increased to 9.6 mmol/L at 1 h after perfusion, and then gradually decreased. The creatine kinase level was increased at the start of perfusion, reached the peak at 2 h up to 20 030 U/L, then decreased and remained stable at the end of perfusion. At the end of perfusion, the morphology of muscle fibers was normal, the gap among muscle fibers was expanded slightly, and the glycogen of skeletal muscles was not significantly accumulated. At 0 h perfusion, the number of apoptotic cells in vascular endothelial cells was large, which was declined at 6 h perfusion. Evident vascular filling was observed at 0 h, and the filling degree of some finger-tip vessels was decreased at 6 h. Conclusions Normothermic mechanical perfusion of severed human limbs with red blood cells from humanized genetically modified pigs may continuously and stably supply energy and oxygen, adjust the ion pH balance of perfusion solution, maintain normal cellular metabolism and exerts certain protective effect upon severed human limbs. [ABSTRACT FROM AUTHOR]

Pseudorabies virus is a major pathogen in the pig industry, causing substantial economic losses. The emergence of pseudorabies virus variant strains in China has led to extensive spread, raising concerns about their potential impact. However, the differences in pathogenicity between the classical strains and the variant strains of genotype II are not well understood. In this study, we isolated three pseudorabies virus strains to evaluate their replication characteristics and to examine the differences in virulence genes among various subgenotypes strains. Additionally, a piglet infection model was utilized to investigate the clinical features of infection, tissue tropism, and the inflammatory responses induced by these strains. Our results showed that the genotype II variant strains (MS, XJ, LS, and CZ) had significantly larger plaque sizes and higher replication capacities than the genotype II classical strain Fa. The animal experiments revealed significant differences in pathogenicity among the pseudorabies virus subgenotype strains, with the variant strains showing higher mortality rates, more severe clinical symptoms, increased nasal virus shedding, and a more robust inflammatory response compared to the genotype II classical strain. There were also notable differences in tissue tropism among the strains. In terms of tissue viral loads, the genotype II variant strains did not exhibit a significant advantage over the genotype I classical strain. Furthermore, our findings indicate that antibodies against the genotype II classical strains have a reduced neutralizing capacity against the genotype II variant strains. On the other hand, antibodies against the genotype II variant strains displayed similar neutralizing abilities against both classical and variant strains. Overall, these findings offer important insights into the distinctions among pseudorabies virus subgenotypes and their implications for the clinical control of pseudorabies virus infections in pig farming. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the influence of N-acetylcysteine (NAC) aerosol inhalation on serum inflammatory factors and immune function in children with upper airway cough syndrome (UACS). Methods: 118 children with UACS who were on admission at Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine, China between September 2021 and February 2023, were enrolled in the study. They were assigned to control and study cohorts, with 59 patients per group. Control group received routine treatment (3 mL of normal saline via nebulized inhalation 2 times/day), while the study group received 3 mL of NAC aerosol inhalation via nebulized inhalation 2 times/day. Both groups were treated for 2 weeks. Thereafter, the two groups were compared with respect to total treatment effectiveness, cough symptom and Lund-Kennedy ratings, levels of inflammatory factors (interleukin-13 (IL-13), interleukin-27 (IL-27), C-reactive protein (CPR)) and concentrations of immune function indices (CD3 +, CD4 + and CD8 +) before and after treatment, and adverse reactions. Results: Treatment effectiveness (efficacy) was significantly higher (p < 0.05) in study cohort than in control cohort (89.83 vs 71.19 %). The 2 cohorts had significant reductions in scores on cough symptoms and Lund-Kennedy, with smaller values in study cohort. In both groups, the levels of IL-13 and CPR were decreased, while IL-27 level was increased. Levels of IL-13 and CPR in study group were significantly lower than those in control group, while IL-27 level was significantly higher than that in control group (p < 0.05). Conclusion: N-acetylcysteine aerosol inhalation enhances curative effect, relieves clinical symptoms, reduces inflammation, and improves immunity in UACS children, and shows good degree of safety. However, its long-term efficacy needs to be studied. [ABSTRACT FROM AUTHOR]

Sepsis is recognized as a syndrome of systemic inflammatory reaction induced by dysregulation of the body's immunity against infection. The multiple organ dysfunction associated with sepsis is a serious threat to the patient's life. Endothelial cell dysfunction has been extensively studied in sepsis. However, the role of macrophages in sepsis is not well understood and the intrinsic link between the two cells has not been elucidated. Macrophages are first-line cells of the immune response, whereas endothelial cells are a class of cells that are highly altered in function and morphology. In sepsis, various cytokines secreted by macrophages and endothelial cell dysfunction are inextricably linked. Therefore, investigating how macrophages affect endothelial cells could offer a theoretical foundation for the treatment of sepsis. This review links molecules (TNF-α, CCL2, ROS, VEGF, MMP-9, and NO) secreted by macrophages under inflammatory conditions to endothelial cell dysfunction (adhesion, permeability, and coagulability), refining the pathophysiologic mechanisms of sepsis. At the same time, multiple approaches (a variety of miRNA and medicines) regulating macrophage polarization are also summarized, providing new insights into reversing endothelial cell dysfunction and improving the outcome of sepsis treatment. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to evaluate the application of choledochoscopy combined with double-cannula lavage in the treatment of acute pancreatitis (AP) with encapsulated necrosis and analyzed related inflammatory indexes. Methods: Thirty patients with AP with encapsulated necrosis were enrolled and treated with choledochoscopy and double-cannula lavage. Serum white blood cell (WBC), procalcitonin (PCT), C-reactive protein (CRP), interleukin 6 (IL-6), IL-8, tumor necrosis factor alpha (TNF-α), and related inflammatory indexes were detected before and after surgery. Results: All of the participants who underwent the surgery recovered well and were discharged without serious complications; no deaths occurred. The serum WBC, PCT, and CRP of patients after surgery decreased compared with before the procedure, and the differences in WBC and CRP were statistically significant (P < 0.05); the difference in PCT was not statistically significant (P > 0.05). Postoperatively, IL-6, IL-8, and TNF-α levels were higher than before surgery, and the differences were statistically significant (P < 0.05). Conclusion: The surgical method presented herein effectively controlled and alleviated the infection of patients; it also did not increase the risk of infection and can thus be considered a safe and effective surgical method. [ABSTRACT FROM AUTHOR]

BACKGROUND: Long non-coding RNAs (lncRNAs), as important regulators of the inflammatory response, are involved in the immune-inflammation-brain crosstalk mechanism after ischemic stroke and have the potential to become a therapeutic agent for neurological dysfunction after ischemic stroke. OBJECTIVE: To analyze and summarize the molecular mechanism of lncRNA acting on glial cells involved in the neuroimmuno-inflammatory cascade response after ischemic stroke and the associated signaling pathways, pointing out that lncRNAs have the potential to regulate inflammation after ischemic stroke. METHODS: PubMed was searched using the search terms of “ischemic stroke, long non-coding RNA, neuroinflammation, immune function, signal pathway, microglia, astrocytes, oligodendrocyte, mechanism,” and 63 relevant documents were finally included for review. RESULTS AND CONCLUSION: In the early stage of ischemic stroke, the death of nerve cells due to ischemia and hypoxia activates the innate immune response of the brain, promoting the secretion of inflammatory factors and inducing blood-brain barrier damage and a series of inflammatory cascades responses. As an important pathogenesis factor in ischemic stroke, the neuroimmuno-inflammatory cascade has been proved to seriously affect the prognosis of patients with ischemic stroke, and it needs to be suppressed promptly in the early stage. Neuroinflammation after ischemic stroke usually induces abnormal expression of a large number of lncRNAs that mediate a series of neuro-immune-inflammatory crosstalk mechanisms through regulating the polarization of microglia, astrocytes and oligodendrocytes to exert post-stroke neuroprotective effects. LncRNAs, as important regulatory factors of the inflammatory response, inhibit the neuroimmuno-inflammatory cascade response after ischemic stroke through regulating nuclear factor-κB, lncRNA-miRNA-mRNA axis, Rho-ROCK, MAPK, AKT, ERK and other signaling pathways to effectively improve neurological impairment after ischemic stroke. Most of experimental studies on the interaction between lncRNAs and ischemic stroke are based on a middle cerebral artery occlusion model or a cerebral ischemia-reperfusion injury model, but no clinical trials have been conducted. Therefore, it remains to be further explored about whether lncRNAs can be safely applied in clinical practice. At present, there are many therapeutic drugs for the treatment of ischemic stroke, but there are relatively few studies on the application of lncRNAs, exosomes and other transplantation technologies for the treatment of ischemic stroke using tissue engineering technology, which need to be further explored. lncRNA has become an important target for the treatment of ischemic stroke with its relative stability and high specificity. In future studies, more types of inflammatory lncRNAs that function under ischemic-hypoxia conditions should continue to be explored, in order to provide new research directions for the treatment of neuroinflammation after ischemic stroke. [ABSTRACT FROM AUTHOR]

BACKGROUND: Mitochondrial reactive oxygen bursts have been shown to play a key role in skeletal muscle ischemia-reperfusion injury. 3-Nitro-Nmethylsalicylamide (3-NNMS) can effectively reduce the electron transport rate and has a potential protective effect on limb ischemia-reperfusion injury, but there is no clear research and clinical application. OBJECTIVE: To investigate the protective effect of 3-NNMS on the skeletal muscle after limb ischemia-reperfusion injury in rats and its mechanism. METHODS: Forty healthy 8-week-old Sprague-Dawley rats were randomly divided into control group, 0, 25 and 125 μg/mL 3-NNMS groups, with 10 rats in each group. Animal models of limb ischemia-reperfusion injury were prepared in the latter three groups. 3-NNMS was injected into the injury site 30 minutes before reperfusion. The animals were sacrificed 2 hours after reperfusion. Blood from the apical part of the heart, and the tissue of the rectus femoris muscle of the right lower limb were taken for testing. The pathological morphology of the rectus femoris muscle was detected by hematoxylin-eosin staining. Serum levels of creatine kinase found in the skeletal muscle (CK-MM), lactate dehydrogenase, and myeloperoxidase were detected using ELISA; the levels of nuclear factor κB, tumor necrosis factor α, interleukin 1β, cyclooxygenase 2, malondialdehyde, reactive oxygen species, superoxide dismutase, catalase and glutathione peroxidase in the rectus femoris muscle were measured; and adenosine triphosphate (ATP) level, ATPase activity, and mitochondrial respiratory control rate were tested. RESULTS AND CONCLUSION: Compared with the control group, the model rats with ischemia-reperfusion injury had increased serum levels of CK-MM, lactate dehydrogenase, and myeloperoxidase, increased levels of nuclear factor κB, tumor necrosis factor α, interleukin 1β, cyclooxygenase 2, malondialdehyde and reactive oxygen species in the rectus femoris muscle, decreased levels of catalase and glutathione peroxidase in the rectus femoris muscle, and reduced ATPase activity and mitochondrial respiratory control rate. Moreover, cell morphology was irregular, inflammatory cell infiltration was obvious, and the cells were swollen in rats after ischemia-reperfusion injury. Compared with the 0 μg/mL group, the serum CK-MM and lactate dehydrogenase levels decreased, the levels of nuclear factor κB and cyclooxygenase 2 in the rectus femoris muscle decreased, reactive oxygen species level decreased, and superoxide dismutase activity increased in the 25 μg/mL group; cell morphology was more regular, inflammatory cell infiltration was lighter, and cell swelling was alleviated. Compared with the 0 μg/mL group, the 125 μg/mL group had a reduction in the serum levels of CK-MM, lactate dehydrogenase, and myeloperoxidase and the levels of nuclear factor κB, tumor necrosis factor α, cyclooxygenase 2, malondialdehyde and reactive oxygen species in the rectus femoris muscle, as well as an increase in the levels of superoxide dismutase and glutathione peroxidase in the rectus femoris muscle, and mitochondrial respiratory control rate. Moreover, the cells were arranged neatly, the outline was clear and complete, and the inflammatory cell infiltration was light. To conclude, 3-NNMS can alleviate the functional impairment of the skeletal muscle caused by limb ischemia-reperfusion, and its mechanism of action may be through improving mitochondrial function, reducing reactive oxygen species production, decreasing oxidative stress and inflammatory response, and thus reducing tissue damage and repairing skeletal muscle function. [ABSTRACT FROM AUTHOR]

Objective To investigate the efficacy of Yiqi Huoxue Huayu Decoction combined with dapagliflozin in the treatment patients with of type 2 diabetes mellitus (T2DM) complicated with chronic heart failure(CHF) and its effects on blood glucose control, cardiac function, inflammatory factors and oxidative stress. Methods A total of 116 T2DM patients complicated with CHF admitted to Xinzheng Public People's Hospital from June 2022 to December 2023 were selected and divided into the traditional Chinese medicine (TCM) com- bination group and the dapagliflozin group by random number table method, with 58 cases in each group. The dapagliflozin group was treated with dapagliflozin, and the TCM combination group was treated with Yiqi Huoxue Huayu Decoction combined with dapagliflozin. After eight weeks of treatment, the clinical efficacy. blood glucose control [fasting blood glucose (FBG), 2 h postmeal blood glucose (2 hPG), glycated hemoglobin HbAlc) level,cardiac function indexes [heart rate, left ventricular ejection fraction (LVEF),6 min walking distance, N-terminal B-type natriuretic peptide(NT-proBNP) and inflammatory factors interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-a(TNF-α)], oxidative stress indexes [ma- londialdehyde(MDA), nitric oxide (NO), catalase (CAT), superoxide dismutase (SOD)]. Results After 8 weeks of treatment, the total clinical effective rate of TCM combination group was 96.55% (56/58), which was higher than 84.48% (49/58) of the dapagliflozin group, and the difference was statistically significant (P<0.05). After 8 weeks of treatment, the levels of FBG, 2 hPG, HbAlc, heart rate and plasma NT-proBNP in the TCM combination group were lower than those in the dapagliflozin group, while LVEF and 6 min walking distance were higher than those in dapagliflozin group, the differences were statistically significant (P< 0.05). After 8 weeks of treatment, the serum levels of IL-6,hs-CRP, TNF-α and MDA in the TCM combination group were lower than those in the dapagliflozin group, and the serum levels of NO, CAT and SOD were higher than those in the dapagliflozin group, with statistical significance (P<0.05). During the treatment, the total incidence of adverse reactions in the TCM combination group was 6.90% (4/58), which was slightly lower than 13. 79% (8/58) in the dapagliflozin group, but with no statistical significance (P>0.05). Conclusion Yiqi Huoxue Huayu Decoction combined with dapagliflozin has a significant effect in the treatment of T2DM patients with CHF, which can effectively regulate blood glucose, improve cardiac function, alleviate oxidative stress and reduce inflammation, with high safety. [ABSTRACT FROM AUTHOR]

BACKGROUND: Spheroid culture of mesenchymal stem cells in bioreactors is an in vitro culture method to maintain their stemness properties and allow for large-scale expansion. Clarifying its effects on the immunoregulation effect of stem cells is beneficial for their clinical application. OBJECTIVE: To investigate the effects of spheroid culture in a rotating bioreactor on the secretion of inflammatory factors by human placenta-derived mesenchymal stem cells. METHODS: Placenta-derived mesenchymal stem cells isolated from human placenta tissue were cultured in two-dimensional culture or a rotating bioreactor culture. Cell morphology and proliferation ability were observed using inverted phase contrast microscopy, immunohistochemical staining, and CCK-8 assay. The gene expression and protein secretion of several inflammatory factors were detected by RT-qPCR and flow immunofluorescence assay. RESULTS AND CONCLUSION: (1) Mesenchymal stem cells cultured in a rotating bioreactor aggregated into multicellular spheroids, which gradually increased in number and volume. (2) The hematoxylin-eosin staining results showed that the mesenchymal stem cells cultured in the rotating bioreactor for 4 days were evenly distributed and had normal morphology in the spheroids. (3) Immunohistochemical staining results revealed many mesenchymal stem cells with Ki)67 positive in the spheroids. (4) The CCK-8 assay results exhibited that the viability of mesenchymal stem cells derived from spheroid culture was significantly higher than that of cells cultured in two-dimensional culture. (5) The results of RT-qPCR and flow immunofluorescence assay demonstrated that the gene expression and protein secretion (interleukin 1β, interleukin-4, interleukin-6, interleukin-8, interleukin-10, interleukin-17, tumor necrosis factor α and interferon α) of inflammatory factors derived from mesenchymal stem cells cultured in the rotating bioreactor were significantly higher than those in two-dimensional culture. (6) Our results indicate that spheroid culture in a rotating bioreactor can significantly elevate the secretion ability of various inflammatory factors by human placenta-derived mesenchymal stem cells, and enhance the immunoregulatory effect of human placenta-derived mesenchymal stem cells. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of Fu-Fang-Yu-Jie （FFYJ） granules on LPS-induced inflammation model in bone marrow-derived macrophages （BMDM） and its intervention of FFYJ on nucleotide-bound oligomeric domain-like receptor protein 3（ NLRP3） inflammatory signaling pathway in macrophages. Methods: Primary cells were extracted and isolated from the leg bone marrow of C57BL/6 mice and BMDM macrophages were obtained after 7 days of induction with 50 ng/ml M-CSF. Groups included control group （Control）， model group （LPS+ATP）， FFYJ low dose group （FFYJ 50 μg/ml）， FFYJ medium dose group （FFYJ 100 μg/ml）， FFYJ high dose group （FFYJ 200 μg/ml） and positive drug dexamethasone group （DEX）. BMDM in FFYJ treatment group and positive drug group were pretreated for 1 hour before modeling. Lactate dehydrogenase （LDH） release assay was used to detect the level of LDH in the supernatant of each group of cells； ELISA was used to detect the level of inflammatory factors TNF-α， IL-6 and IL-1β in the supernatant of each group of cells； qRT-PCR was used to detect the levels of TNF- α， IL-6 and IL-1β in each group of cells； protein levels of NF-κB， p-NF-κB， NLRP3， Caspase-1 p45， Caspase-1 p20 and GSDMD-N in each group of cells were detected by Western blot； inverted fluorescence microscope was used to observe the cell pyroptosis of each group after Hoechst-PI staining. Results: Compared with control group， the levels of LDH， TNF-α， IL-6 and IL-1β in the supernatant of the model group were signifidoi cantly higher （P<0.000 1）； the mRNA levels of TNF-α， IL-6 and IL-1β in the model group were significantly higher （P<0.000 1）； the protein levels of p-NF-κB， NLRP3， Caspase-1 p20 and GSDMD-N were significantly higher（ P<0.05）； and the number of PI-positive cells was significantly higher （P<0.05）. Compared with the model group， FFYJ and DEX significantly reduced the levels of LDH， TNF-α， IL-6 and IL-1β in the supernatant of BMDMs （P<0.05）； down-regulated the mRNA levels of TNF-α， IL-6 and IL-1β in the cells （P<0.05）； and inhibited the expressions of p-NF- κB， NLRP3， Caspase-1 p20 and GSDMD-N protein expressions （P<0.05）； and significantly reduced the number of PI-positive cells （P<0.05）. Conclusion: FFYJ exerts anti-inflammatory effects by inhibiting NLRP3 inflammasome activation in BMDM macrophages. [ABSTRACT FROM AUTHOR]

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BackgroundSchizophrenic patients have metabolic disorders， impaired language and information processing function. Inflammatory factors may play an important role in the occurrence and development of schizophrenia.ObjectiveTo explore the relationship of the inflammatory factor levels with metabolic levels， language fluency and information processing function in patients with schizophrenia， so as to provide references for clinical understanding of the neuropathological mechanisms of schizophrenia.MethodsA total of 96 patients with schizophrenia were included in the study group， who were hospitalized in the Fourth People's Hospital of Hefei from January 2021 to December 2022 as well as met the diagnostic criteria of Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） and Mini-International Neuropsychiatric Interview （MINI） 6.0 .Meanwhile， population who underwent physical examination at the same hospital were included in the control group （n=42）. A high-sensitivity multi factor electrochemiluminescence analyzer was used to detect the levels of inflammatory factors IL-4， IL-5， IL-7， IL-8， IL-10 and IL-13. A fully automated biochemical analyzer was used to detect the levels of metabolic indicators such as fasting blood glucose， triglycerides， high-density lipoprotein， apolipoprotein A， creatinine and urea nitrogen. Verbal fluency and information processing function of all participants were assessed by using Verbal Fluency Test （VFT） and Stroop Color Word Test （SCWT）.ResultsThere were statistically significant differences in the levels of IL-4， IL-5， IL-7， IL-8， IL-10， IL-13 and IL-15 between the study group and the control group （P

Abstract Kumquat pomace non‐extractable polyphenols (KNEP), which contains celobiotics and has anti‐inflammatory and antioxidant effects, are one of the main components in kumquats. We aimed to determine the preventive and inhibitory effects of KNEP on dextran sodium sulphate (DSS)‐induced inflammatory bowel disease (IBD). The disease activity index (DAI) score, H&E staining, high‐throughput sequencing technology, quantitative analysis, ELISA, and western blotting were used to explore the effect of KNEP in an IBD mouse model. The DAI score and H&E staining results showed that compared with the DSS treatment group, the DAI and pathological status of IBD in the DSS + 3% KNEP (low‐dose) and DSS + 6% KNEP (high‐dose) intervention groups were significantly improved. High‐throughput sequencing showed that the composition of the intestinal flora was restored under KNEP, and the abundance of pathogenic bacteria decreased and that of beneficial bacteria increased. Quantitative analysis of short‐chain fatty acids (SCFAs) showed that the SCFAs content in the cecum of IBD mice increased in a dose‐dependent manner. ELISA results showed that KNEP at different doses could inhibit the expression of TNF‐α, IL‐1β, IFN‐γ, and other inflammatory factors, and that 6% KNEP had the most potent inhibitory effect. Western blotting results showed that KNEP inhibited the expression of TLR4, NF‐κB, and NLRP3 in the colon of mice with DSS‐induced colitis in a dose‐dependent manner. These results indicate that KNEP can significantly improve DSS‐induced acute colitis in mice, and the higher the KNEP content, the more pronounced the improvement in IBD.

BACKGROUND: Long intergenic non-protein coding RNA 00707 (LINC00707) and microRNA-423-5p (miR-423-5p) are both involved in the occurrence and development of osteoarthritis. Starbase predicts that LINC00707 and miR-423-5p have complementary sequences, but whether LINC00707 and miR-423-5p interact to regulate the progress of osteoarthritis still needs further research. OBJECTIVE: To investigate whether LINC00707 targets miR-423-5p to affect chondrocyte injury and inflammatory factor secretion in osteoarthritis. METHODS: Articular chondrocytes were divided into eight groups: (1) blank control group was given no treatment; (2) interleukin (IL)-1β group was cultured with 10 ng/mL IL-1β for 48 hours; (3) IL-1β+si-NC group was transfected with si-NC and then treated with 10 ng/mL IL-1β for 48 hours; (4) IL-1β+si-LINC00707 group was transfected with si-LINC00707 and then treated with 10 ng/mL IL-1β for 48 hours; (5) IL-1β+miR-NC group was transfected with miR-NC and then treated with 10 ng/mL IL-1β for 48 hours; (6) IL-1β+miR-423-5p group was transfected with miR-423-5p mimic and then treated with 10 ng/mL IL-1β for 48 hours; (7) IL-1β+si-LINC00707+anti-miR-NC group was co-transfected with si-LINC00707 and anti-miR-NC and then treated with 10 ng/mL IL-1β for 48 hours; (8) IL-1β+si-LINC00707+anti-miR-423-5p group was co-transfected with si-LINC00707 and anti-miR-423-5p and then treated with 10 ng/mL IL-1β for 48 hours. Relevant tests were performed at the end of the intervention. RESULTS AND CONCLUSION: Compared with the blank control group, the mRNA expression of LINC00707, apoptosis rate, protein expression of C-caspase3 and C-caspase9, and levels of tumor necrosis factor-α and IL-6 in articular chondrocytes were increased in the IL-1β group, while there was a decrease in miR-423-5p expression and IL-10 level (P < 0.05). Compared with the IL-1β group, the mRNA expression of LINC00707, apoptosis rate, protein expression of C-caspase3 and C-caspase9, and levels of tumor necrosis factor-α and IL-6 in articular chondrocytes were decreased in the IL-1β+si-LINC00707 group, while miR-423-5p expression and IL-10 level increased (P < 0.05). Compared with the IL-1β+miR-NC group, the protein expression of C-caspase3 and C-caspase9 and levels of tumor necrosis factor-α and IL-6 in articular chondrocytes were decreased in the IL-1β+miR-423-5p group, while miR-423-5p expression and IL-10 level increased (P < 0.05). Compared with the IL-1β+si-LINC00707+anti-miR-NC group, apoptosis rate, protein expression of C-caspase3 and C-caspase9, and levels of tumor necrosis factor-α and IL-6 in articular chondrocytes were increased in the IL-1β+si-LINC00707+anti-miR-423-5p group, while miR-423-5p expression and IL-10 level decreased (P < 0.05). To conclude, inhibiting LINC00707 by targeting miR-423-5p can reduce IL-1β-induced apoptosis and inflammation in articular chondrocytes. [ABSTRACT FROM AUTHOR]

BACKGROUND: Gastrodin has anti-inflammatory effects and is mainly used in clinical practice for the treatment of ischemic stroke, and its mechanism of action is still unclear. OBJECTIVE: To explore the mechanism of gastrodin intervention on inflammatory injury in ischemic stroke rats.METHODS: Fifty Sprague-Dawley rats were divided into sham-operated group, model group, positive control group, high-dose gastrodin group and low-dose gastrodin group by the randomized numerical method, with 10 rats in each group. Ischemic stroke models were established by the middle cerebral artery occlusion method in all groups of rats except for the sham operation group. Administration in each group started on the 3rd day after surgery, and the rats in the positive control group were intraperitoneally injected with edaravone injection (6 mg/kg), the rats in the high- and low-dose gastrodin groups were intraperitoneally injected with 50 and 10 mg/kg gastrodin injection respectively, and the rats in the sham-operated and model groups were intraperitoneally injected with the equal volume of physiological saline. After 14 days of continuous treatment in each group, the pathological changes in rat brain tissue were observed, and the positive expression of NLRP3 inflammasome and the expression of inflammatory response-related proteins and their mRNAs were detected. RESULTS AND CONCLUSION: Compared with the sham-operated group, the volume of cerebral infarction became larger in the model group; the structure of brain tissue was loose, irregular cavities could be observed, and the number of neurons was reduced and irregularly arranged; the positive expression of NLRP3 inflammasome increased (P < 0.01); and the protein and mRNA expression levels of Toll-like receptor 4, myeloid differentiation factor 88, apoptosis-associated speck-like protein containing a caspase-recruitment domain, Caspase-1, and interleukin-1β increased (P < 0.01). Compared with the model group, the volume of cerebral infarction became smaller in the high- and low-dose gastrodin groups; the neurons were regularly arranged, increased in number, and uniformly distributed; the positive expression of NLRP3 inflammasome was decreased (P < 0.05); the protein and mRNA expression levels of Toll-like receptor 4, myeloid differentiation factor 88, apoptosis-associated speck-like protein containing a caspase-recruitment domain, Caspase-1, and interleukin-1β were decreased in the high-dose gastrodin group (P < 0.01); Toll-like receptor 4 protein expression showed no significant changes in the low-dose gastrodin group, and the protein and mRNA expression of the other inflammatory response-associated factors decreased (P < 0.05, P < 0.01). To conclude, gastrodin attenuates inflammatory injury in ischemic stroke rats, and its mechanism of action may be related to the inhibition of inflammatory response-associate factor expression. [ABSTRACT FROM AUTHOR]

Yue Han,&ast; Jingyi Wang,&ast; Jin Zhang,&ast; Xi Zheng, Yijia Jiang, Wei Liu, Wenxiong Li Department of Surgical Intensive Care Unit, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenxiong Li, Department of Surgical Intensive Care Unit, Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Chaoyang District, Beijing, 100020, People’s Republic of China, Tel +86 136 0109 7813, Email liwx1126@163.comPurpose: Sepsis-associated acute kidney injury (S-AKI) contributes to high mortality, but it is lack of specific treatments. We aimed to investigate the underlying mechanism of S-AKI and to identify target drugs to alleviate AKI.Methods: We establish a stable mouse model of S-AKI by Pseudomonas aeruginosa incision infection. Based on high-throughput sequencing and bioinformatics analysis, we investigated the underlying mechanism and selected the target drug (VX-702) for S-AKI. An in vitro model established by co-cultured of kidney tubular epithelial cell line (TCMK-1) cells with lipopolysaccharide (LPS)-induced leukemic monocyte/macrophage cells (RAW264.7), we explored the effect of VX-702 on S-AKI.Results: The data showed interleukin (IL)-6 and IL-1β were the hub genes, and the mitogen-activated protein kinase (MAPK) signaling pathway was the main pathway involved in S-AKI. Administration of VX-702 by oral gavage decreased the elevated concentrations of IL-6, IL-1β, serum creatinine, and blood urea nitrogen in mice with S-AKI. Moreover, VX-702 reduced the number of apoptotic cells in damaged kidney tissues. Cell viability was decreased, and the number of apoptotic cells was increased in TCMK-1 cells co-cultured with LPS-induced RAW264.7 cells compared to LPS-induced TCMK-1 cells. VX-702 treatment reversed this effect. VX-702 treatment reduced the levels of phosphorylated p38 MAPK and proinflammatory cytokines in RAW264.7 cells and the supernatant. VX-702 could bind IL-6, IL-1β and MAPK, and affect the binding of IL-1β and its receptor, as demonstrated by molecular docking.Conclusion: VX-702 ameliorated S-AKI by inhibiting the release of proinflammatory cytokines from macrophages, indicating its potential as a novel therapeutic for S-AKI treatment.Keywords: sepsis-associated acute kidney injury, VX-702, macrophages, inflammatory factor, MAPK

The complete intestinal structure is important to ensure the rapid and h ealthy growth of fish. However, the feed composition, aquaculture water environment, intestinal microbial population, and other factors may affect the intestinal health of fish. Intestinal health problems caused by feed ingredients are mainly due to the antinutrient factors contained in raw materials. Antinutritional factors contained in high-level soybean meal can cause oxidative damage to the intestine, thus, inducing soybean meal-induced enteritis (SBMIE), which leads to a decreased appetite and the slow growth of fish. Alleviating the damage of soybean meal to the fish intestinal tract and improving intestinal health through nutrition are essential methods for ensuring the sustainable development of the feed industry, which has significant ecological and economic significance.As a functional amino acid, arginine is a precursor to the synthesis of bioactive substances, such as urea, glutamic acid, creatine, proline, polyamine, and nitric oxide. Arginine modulates metabolic regulation, including growth, immunity, intestinal barrier, and endocrine regulation. It plays a vital role in the immune regulation, maintenance, and protection of the intestinal mucosal structure and function. It has been reported that arginine is beneficial for repairing intestinal mucosal injury in poultry and aquatic animals. In this study, the carnivorous marine economic fish Sebastes schlegelii (54.97±0.12) g were used to investigate the repair effect and mechanism of arginine on SBMIE. This study aimed to provide a scientific basis for the application of arginine for maintaining the intestinal health of fish and provide a reference for the application of plant protein to the compound feed of the carnivorous economic fish S. schlegelii.The purpose of this study was to investigate the repairing effects of arginine on the growth performance, arginine metabolism, intestinal structure, antioxidant performance, relative expression levels of intestinal tight junction protein genes (occludin, clnd15, and zo-1), and inflammatory factor-related genes (il-1β, il-8, il-15, and tlr8) and anti-inflammatory factor-related gene (il-12b) of S. schlegelii with SBMIE. S. schlegelii were fed high-level soybean meal (40%) for 28 days to induce SBMIE. SBMIE-S. schlegelii weighing (54.97±0.12) g were used as the study animals. Four isonitrogen and isoenergetic experimental feeds were formulated. The basic formula was supplemented with 30% soybean meal, arginine 0 supplementation as the control group (D0), and 1%, 2%, and 3% arginine supplementation as the treatment groups, named D1, D2, and D3, respectively. Each diet group had three replicates, and each replicate consisted of 40 fish. The fish were randomly placed in 12 homemade cages (60 cm × 60 cm × 90 cm). The experiment lasted for 6 weeks. The experimental fish were fed twice a day (08:00 and 17:00), with the initial feeding amount being 1% of the body weight, and the feeding amount being adjusted according to the feeding situation. During the experiment, the bottom of the cages was cleaned, and the water was changed every day to maintain the water temperature at 18~22 ℃, the dissolved oxygen at > 6 mg/L, the pH at 7.6~8.2, the ammonia nitrogen content at < 0.05 mg/L, and the nitrite nitrogen content at < 0.05 mg/L. The light cycle was the natural cycle. The results showed that the weight gain rate of the fish in the D2 and D3 groups was significantly higher than that in D0 group (P < 0.05). The hepatosomatic and viscerosomatic indexes of the fish in the arginine treatment groups were significantly lower than those in the D0 group, and the condition factor was significantly higher than that in the D0 group (P < 0.05). There was no significant effect on the survival rate (P > 0.05). Diamine oxidase (DAO) activity, NO content, and iNOS activity values in the serum of the treatment groups were significantly lower than those in the D0 group (P < 0.05). The serum T-NOS activity in the D2 and D3 groups was significantly lower than that in the D0 group (P < 0.05). The duplicature height in the treatment groups was significantly higher than that in the D0 group, while no significant difference was found in the duplicature number and muscle thickness (P > 0.05). In group D0, the intestinal mucosa lamina propria widened, and the number of goblet cells increased, while in groups supplemented with arginine, the intestinal mucosa was intact, and the problems mentioned above improved significantly. Intestinal total antioxidant capacity (T-AOC) in arginine supplementation groups was significantly increased, and the highest value was found in group D2 (P < 0.05). The malondialdehyde content in groups D2 and D3 was decreased significantly compared to that in the D0 group (P < 0.05). The relative expression of occludin mRNA in each treatment group was significantly upregulated compared to that in the D0 group (P < 0.05). The relative expression level of clnd15 mRNA in the D2 group was significantly higher than that in the D0 and D1 groups (P < 0.05). The relative expression level of zo-1 mRNA in group D1 was significantly higher than that in the other groups (P < 0.05). The relative expression levels of IL-1β, IL-15, and TLR8 mRNA were downregulated in all treatment groups, while the relative expression of IL-12b mRNA was upregulated (P < 0.05). No significant differences were found in IL-8 mRNA relative expression (P > 0.05). In conclusion, under the conditions of this experiment, the growth and antioxidant performances of S. schlegelii with SBMIE were significantly increased, arginine metabolism and the intestinal structure were improved significantly, and the relative expression of intestinal tight junction protein and anti-inflammatory factor-related genes was upregulated, while that of inflammatory factor-related genes was downregulated, with arginine supplementation in a high-level soybean meal diet. Arginine (2% best) was effective in repairing SBMIE of S. schlegelii. The results of this study provide a theoretical basis for the mechanism of repairing SBMIE with arginine.

Introduction: Premenstrual dysphoric disorder (PMDD), a severe form of premenstrual syndrome (PMS), is a serious health disorder that affects patient moods. It is caused by cyclic psychological symptoms and its pathogenesis is still unclear. Abnormalities in the basolateral amygdala (BLA) orexin system, which are important causes of the development of depressive mood, have not been reported in PMDD, so exploring its intrinsic mechanisms is meaningful for enriching the pathomechanisms of PMDD. Methods: High performance liquid chromatography was used for the determination of the active ingredients of Jingqianshu granules. Developing a rat model of premenstrual depression using the forced swimming test (FST). The experiment consisted of two parts. In Part 1, the rats were divided into the control group, the model group, the model + Jingqianshu group, and the model + fluoxetine group. The FST, open field test, and elevated plus maze test, were used to assess the behavior of the rats as well as to evaluate the effect of drug intervention. Immunofluorescence and RT-qPCR were used to detect the expression of orexin and its receptors OX1R and OX2R genes and proteins. The expression of Toll-like receptor 4, nuclear factor kappa-B, tumor necrosis factor-a, interleukin 6, and interleukin-1ß in the BLA brain region was detected by Western-Blot. In part 2, the rats were injected intracerebrally with orexin-A. Observe the behavioral activities of rats in the control group, model group, and model+orexin-A group. Immunofluorescence was used to detect microglia in the BLA area of rats, and the expression levels of the above inflammatory factors were detected by Western-Blot. Results: The five components of Jingqianshu granules are: paeoniflorin, erulic acid, liquiritin, hesperidin, and paeonol. During the estrous cycle, rats exhibited depressive-like behavior during the non-receptive phase of the behavioral test, which disappeared during the receptive phase. Immunofluorescence and RTqPCR showed reduced gene and protein expression of orexin, OX1R, and OX2R in the BLA region of rats in the model group. WB showed elevated levels of inflammatory factors. All returned to control levels after drug treatment. In part 2, injection of orexin-A into the BLA brain region of model rats resulted in reduced immunoreactivity of microglia and decreased expression levels of inflammatory factors. Discussion: Jianqianshu granules can achieve the purpose of treating premenstrual depression by regulating orexin-mediated inflammatory factors, which provides a new idea for further research on the pathogenesis of PMDD. However, the current study is still preliminary and the pathogenesis of PMDD is complex. Therefore, more in-depth exploration is needed. [ABSTRACT FROM AUTHOR]

Objective To investigate the efficacy of indobuprofen combined with nicodil for the treatment of acute coronary syndromes (ACS) and the effects of percutaneous coronary intervention on patients Effects of myocardial injury markers, platelet function and inflammatory factors after intervention (PCI). Method A total of 150 patients with ACS admitted to the hospital from January 2021 to December 2022 were divided into groups according to different treatment methods. The control group (n = 75) was given nicodil combined with antiplatelet therapy, and the study group (n = 75) was given indobufen combined with nicodil combined with antiplatelet therapy. Both groups were treated for 2 weeks. The clinical efficacy of the two groups was compared, the changes of myocardial injury markers, platelet function and inflammatory factors before and after treatment were monitored, and the total incidence of adverse reactions was recorded. Results The total effective rate of the group treated with nicodil combined with indobufen was 98.67% higher than that of the control group treated with nicodil alone, 90.67% (χ2 = 4.754, P < 0.05). The levels of myocardial injury markers such as cTnI and CK-MB in the study group after treatment were lower than those in the control group (t = 15.492, 3.250, P < 0.05). The levels of platelet function indexes such as CD62p, CD63, GP'b/IIIa in the study group after treatment were lower than those in the control group (t = 2.034, 3.257, 2.221, P < 0.05). The levels of CRP, TNF- α, IL-6 and other inflammatory factors in the study group were lower than those in the control group after treatment (t = 21.862, 3.378, 2.131, P < 0.05). The total incidence of adverse reactions after treatment was 4.00% in the study group and 2.67% in the control group (P > 0.05). Conclusion The efficacy of indobufien combined with nicodil in the treatment of ACS is better than that of nicodil alone, and it can improve myocardial injury and platelet function after PCI, inhibit the release of inflammatory factors, and the incidence of adverse reactions is lower. [ABSTRACT FROM AUTHOR]

Objective To investigate the effect of TRPC5 on intermittent hypoxia-induced myocardial pyroptosis. Methods TRPC5 knock out (TRPC5-/-) and SD rats were each randomly divided into chronic intermittent hypoxia group (CIH group) and normoxia group (Control group) (n = 6 for each group). The myocardial fibrosis in rats was visualized by Masson staining, the levels of serum inflammatory factors were measured by ELISA and the relative expression levels of TRPC 5 and pyroptosis-related proteins were determined by Western blotting. Results Masson staining showed that the collagen volume fraction in the TRPC5-/--CIH group was higher than that in the TRPC5-/--Control group and lower than that in the WT-CIH group. The ELISA results showed that the serum levels of IL-1, IL-6, and TGF- β in the TRPC5-/--CIH group were higher than those in the TRPC5-/--Control group and lower in the WT-CIH group. Western blotting results showed that the relative expression levels of pyroptosis related proteins caspase-1, NLRP3, GSDMD, and GSDMD-N in the TRPC5-/--CIH group were higher than those in the TRPC5-/--Control group and lower than those in the WT-CIH group. Conclusion TRPC5 deficiency alleviates myocardial pyroptosis and myocardial fibrosis induced by hypoxia. [ABSTRACT FROM AUTHOR]

BACKGROUND: Previous studies have shown that human beta-defensin 3 has significant antifungal, antibacterial, and antiviral activities and plays an important bridging role in linking innate and acquired immune responses. OBJECTIVE: To observe the effect of human beta-defensin 3 hydrogel on treatment of periodontitis in rats. METHODS: Using Poloxamer 188 and 407 as the matrix, a blank hydrogel was constructed by cold solution. Human beta-defensin 3 hydrogel was prepared by mixing human beta-defensin 3 with the hydrogel. Twenty-five SD rats were randomly divided into five groups with five rats in each group: No treatment was given in the healthy group. The periodontitis model was constructed by the orthodontic ligature wire method in the periodontitis group, blank hydrogel group, minocycline hydrochloride group, and human beta-defensin 3 hydrogel group. 8 weeks after modeling, blank hydrogel, minocycline hydrochloride, and human β-defensin 3 hydrogel were injected into the buccal and palatal periodontal bags, once a week, and relevant tests were carried out after continuous administration for 4 weeks. RESULTS AND CONCLUSION: (1) Compared with the healthy group, periodontal plaque index, gingival bleeding index, and periodontal probing depth were increased in the periodontitis group (P < 0.01). Compared with the periodontitis group, the periodontal plaque index, gingival bleeding index, and periodontal probing depth of rats were decreased in the minocycline hydrochloride group and the human beta-defensin 3 hydrogel group (P < 0.05). (2) Hematoxylin-eosin staining proved that the hydrogel was not toxic to the rat organism. (3) Stereomicroscopy and Micro CT showed that compared with the healthy group, the root exposure and the distance between enamel cementum boundary and alveolar crest of the periodontitis group were increased (P < 0.05). Compared with the periodontitis group, the root exposure and the distance between enamel cementum boundary and alveolar crest of rats were reduced in the minocycline hydrochloride group and human beta-defensin 3 hydrogel group (P < 0.05). (4) Hematoxylin-eosin, Masson, and tartrate-resistant acid phosphatase staining showed that periodontal inflammation was obvious, fiber structure was disordered and osteoclasts were active in the periodontitis group and blank hydrogel group, while periodontal inflammation was decreased, fiber arrangement was more regular, and osteoclasts were reduced in the minocycline hydrochloride group and human beta-defensin 3 hydrogel group. (5) qRT-PCR showed that compared with the healthy group, the mRNA expressions of interleukin 1β, tumor necrosis factor α, interleukin 6, and inducible nitric oxide synthase were increased in the periodontitis group (P < 0.05). Compared with the periodontitis group, the mRNA expressions of interleukin 1β, tumor necrosis factor α, interleukin 6, and inducible nitric oxide synthase in gingival tissue of rats were decreased in the minocycline hydrochloride group and human beta-defensin 3 hydrogel group (P < 0.05). (6) The results showed that human beta-defensin 3 hydrogel was able to attenuate inflammation in rat periodontal tissues by decreasing the relative expression of inflammatory factors and inhibiting osteoblasts. [ABSTRACT FROM AUTHOR]

Osteoporosis represents a systemic imbalance in bone metabolism, augmenting the susceptibility to fractures among patients and emerging as a notable mortality determinant in the elderly population. It has evolved into a worldwide concern impacting the physical well-being of the elderly, imposing a substantial burden on both human society and the economy. Presently, the precise pathogenesis of osteoporosis remains inadequately characterized and necessitates further exploration. The advancement of osteoporosis is typically linked to the initiation of an inflammatory response. Cells in an inflammatory environment can cause inflammatory death including pyroptosis. Pyroptosis is a recently identified form of programmed cell death with inflammatory properties, mediated by the caspase and gasdermin families. It is regarded as the most inflammatory form of cell death in contemporary medical research. Under the influence of diverse cytokines, macrophages, and other immune cells may undergo pyroptosis, releasing inflammatory factors, such as IL-1β and IL-18. Numerous lines of evidence highlight the pivotal role of pyroptosis in the pathogenesis of inflammatory diseases, including cancer, intestinal disorders, hepatic conditions, and cutaneous ailments. Osteoporosis progression is frequently associated with inflammation; hence, pyroptosis may also play a role in the pathogenesis of osteoporosis to a certain extent, making it a potential target for treatment. This paper has provided a comprehensive summary of pertinent research concerning pyroptosis and its impact on osteoporosis. The notion proposing that pyroptosis mediates osteoporosis via the inflammatory immune microenvironment is advanced, and we subsequently investigate potential targets for treating osteoporosis through the modulation of pyroptosis. [ABSTRACT FROM AUTHOR]

Objective: Given the high incidence of sarcopenia among Asians, it is imperative to identify appropriate intervention methods. The International Clinical Practice Guidelines for Sarcopenia, developed by the International Conference on Sarcopenia and Frailty Research (ICFSR) task force, recommends resistance training (RT) as a primary treatment for managing sarcopenia. Inflammatory biomarkers serve as indicators of sarcopenia. However, there is currently insufficient conclusive evidence regarding the effectiveness of RT in modulating inflammatory biomarker levels among Asian participants with sarcopenia. Data sources: Four databases were utilized for this study until October 9, 2023. This study focused on randomized controlled trials (RCTs) that examined the effects of RT on interleukin-6 (IL-6), tumor necrosis factor-a (TNF-a), C-reactive protein (CRP), and interleukin-10 (IL-10) about sarcopenia. This study has been registered in the PROSPERO database (CRD42024501855). Results: The meta-analysis included six studies from Asians involving 278 participants. The results showed a significant decrease in RT for IL-6 (weighted mean difference (WMD) = -0.73, 95% confidence interval (CI) = -1.02 to -0.44; n=5). However, no significant differences were found for TNF-a (WMD = -1.00, 95% CI = -2.47 to 0.46; n=5), CRP (WMD = -0.45, 95% CI = -1.14 to 0.23; n=3), and IL-10 (WMD = 0.13, 95% CI = -3.99 to 4.25; n=2). Subgroup analysis revealed that factors including gender selection, intervention methods, frequency, period, and duration could have a particular effect on the part of inflammatory biomarkers. Conclusion: RT has been shown to reduce part of the level of inflammatory markers, specifically IL-6, in Asian sarcopenia participants. However, other inflammatory factors, such as TNF-a, CRP, and IL-10, did not show significant changes. Further research should confirm the impact of RT on these indicators and explore the potential effects of various factors on different inflammatory markers, such as diet, body composition, and medications. [ABSTRACT FROM AUTHOR]

Commonly plaguing in the frigid zone of the world, vitamin D deficiency, as indicated by low levels of 25-hydroxyvitamin D, exacerbated inflammatory responses and impaired endothelial function. Leukoaraiosis (LA) is a prevalent cause of cognitive dysfunction in the elderly and is potentially associated with inflammatory responses. This study aimed to investigate the impact of vitamin D on the severity of LA. Patients with LA were categorized based on 3.0 T brain MRI findings into mild (N = 43), moderate (N = 40), or severe groups (N = 29) using the Fazekas scale (scoring 1-6). A control group consisting of 41 healthy individuals was included. Serum fibrinogen C, homocysteine, plasma 25-hydroxyvitamin D, and intercellular cell adhesion molecule-1 (ICAM-1) levels were measured using ELISA. All LA severity groups exhibited lower plasma 25-hydroxyvitamin D levels compared to the control group, with a more pronounced decrease observed as LA severity increased. Low plasma 25-hydroxyvitamin D was identified as an independent risk factor for LA (P < 0.05) according to Multiple logistic regression analysis. Additionally, a negative association was observed between 25-hydroxyvitamin D and vascular inflammatory factor ICAM-1. Disease severity positively correlated with levels of the inflammatory marker ICAM-1, worsening as plasma 25-hydroxyvitamin D concentration decreased. Low 25-hydroxyvitamin D emerged as an independent risk factor for LA, potentially exacerbating the inflammatory response. These findings suggest 25-hydroxyvitamin D supplementation as a potential therapeutic approach for LA. [ABSTRACT FROM AUTHOR]

Objective To investigate the mechanism of inhibiting titanium partical-induced osteolysis around the skull with arctiin (ARC) in mice based on the changes of inflammatory factors and gut microbiota. Methods Twenty 7-week-old C57BL/6J female mice were randomly and evenly assigned to the following groups: blank group (SHAM), model group (Vehicle), ARC low-dose group, (L-ARC) and ARC high-dose group (H-ARC). During the following 14 days, mice in the experimental group were injected intraperitoneally with two different concentrations of ARC [5 and 10 mg/(kg·d)], respectively. Mice in the sham group and vehicle group were injected with 0.9 % NaCl every day. The following parameters of skulls, BMD, BV/TV, Tb.N, BS/BV, Tb.Sp, and Tb.Th were detected with micro-CT. The levels of TRACP5b, CTX, OCN, IL-6, TNF-α, and IL-10 in serum were detected with ELISA. 16S rRNA sequencing was used to analyze the structure and abundance of gut microbiota. Results BMD, BV/TV, Tb.N, BS/BV, Tb.Th, OCN, and IL-10 decreased significantly in Vehicle group compared to those in SHAM group (P<0.01, P<0.05). Tb.Sp, TRACP5b, CTX, IL-6, and TNF-α significantly increased (P<0.05, P<0.01). Compared to those in Vehicle group, BMD, BV/TV, Tb.N, BS/BV, Tb.Th, and OCN in L-ARC group had an increasing trend (P>0.05), Tb.Sp, TRACP5b, and CTX had a decreasing trend (P<0.05), TNF-α and IL-6 significantly decreased (P<0.05), and IL-10 significantly increased (P<0.05). Compared to those in Vehicle group, the levels of BMD, BV/TV, Tb.N, and IL-10 in H-ARC group significantly increased (P<0.05, P<0.01), the levels of TRACP5b, CTX, IL-6, and TNF-α significantly decreased (P<0.05, P<0.01), while the levels of BS/BV, Tb.Th, and OCN had an increasing trend (P>0.05), and Tb.Sp had a decreasing trend (P>0.05). At the phylum level, compared to that in SHAM group, firmicutes/bacteroidota (F/B) ratio had an increasing trend in Vehicle group (P>0.05). However, compared to that in Vehicle group, the F/B ratio in L-ARC and H-ARC groups significantly decreased (P<0.01). At the genus level, compared to that in SHAM group, the abundance of ileibacterium in Vehicle group had an increasing trend (P>0.05), the abundance of prevotellaceae_UCG-001 and rikenellaceae_RC9 in gut in Vehicle group had a decreasing trend (P>0.05). While compared to that in Vehicle group, the abundance of ileibacterium in ARC groups significantly decreased (P<0.05), the abundance of prevotellaceae UCG-001 and rikenellaceae RC9 in gut in ARC groups significantly increased (P<0.05). Conclusion ARC inhibits titanium partical-induced osteolysis in mice by suppressing inflammation and modulating the structure of gut microbiota in a dose-dependent manner. [ABSTRACT FROM AUTHOR]

Intestinal barrier dysfunction is an important contributor to morbidity caused by sepsis. This study investigates the molecular mechanism by which Ghrelin affects intestinal dysfunction in rat model of sepsis. A rat model of sepsis was established by cecal ligation and puncture (CLP), revealing that Ghrelin was downregulated when sepsis occurs. Increases in the levels of inflammatory factors tumor necrosis factor α (TNF-α), interleukin-1 (IL-1β), IL-6, gastrin, γ-H2AX and 8-OHdG was also detected in this model system, as was an overall increase in oxidative stress. Introduction of exogenous Ghrelin inhibited these increases in inflammatory response and oxidative stress, leading to a reduction of overall sepsis-induced intestinal dysfunction. Ghrelin was then shown to activate SIRT1 expression in vitro, while SIRT1 was found to co-express with KLF4, which in turn was predicted to bind to matrix metalloproteinase 2 (MMP2) promoter. Finally, gainand loss-of-function experiment demonstrated that SIRT1 upregulated the expression of KLF4 to downregulate MMP2. Collectively, Ghrelin inhibits the oxidative stress and intestinal dysfunction to attenuate sepsis by activating SIRT1 and regulating a KLF4/MMP2 regulatory axis. [ABSTRACT FROM AUTHOR]

Objective To investigate the efficacy of compound polymyxin B ointment (TAO) combined with recombinant bovine basic fibroblast growth factor (rh-bFGF) gel in the treatment of patients with deep second degree burns. Methods A total of 60 patients with deep Ⅱ degree burn admitted to our hospital from January to November 2022 were selected and divided into observation group and control group by random number table method, with 30 patients in each group. The control group was treated with TAO,and the observation group was treated with rh-bFGF gel. The clinical efficacy, symptom disappearance time, wound healing time, dressing pain, inflammatory factors, incidence of complications, and quality of life were compared between the two groups. Results The total effective rate of the observation group was significantly higher than that of the control group, the incidence of complications was significantly lower than that of the control group, the degree of pain was significantly lighter than that of the control group, the swelling disappearance time, erythema disappearance time, exudate disappearance time, blister disappearance time, pain disappearance time and wound healing time were significantly shorter than those of the control group, the differences were statistically significant (P＜0. 05) . There was no significant difference being found in the comparison of inflammatory factors and quality of life between the two groups before treatment (P＞0. 05) . After treatment, the levels of procalcitonin and C-reactive protein in the observation group were significantly lower than those in the control group. The scores of basic living ability dimension, hand function dimension, emotional dimension, interpersonal relationship dimension, sexual life dimension, body heat dimension, heat sensitivity dimension, cooperation treatment dimension and work dimension in the simplified burn health scale were significantly higher than those in the control group, and the differences were statistically significant (P＜0. 05) . Conclusion TAO combined with rh-bFGF gel is effective in the treatment of patients with deep Ⅱ degree burn. It can accelerate the disappearance of symptoms and wound healing, reduce the pain and inflammatory reaction of dressing change, reduce the incidence of complications and improve the quality of life of patients. [ABSTRACT FROM AUTHOR]

BACKGROUND: M2 macrophages have the function of reducing inflammatory factors and promoting tissue healing. Therefore, how to regulate M2 polarization of macrophages has been a hot research topic in recent years, and some miRNAs have been found to have this function. OBJECTIVE: To investigate the effects of miR-378a on the polarization of the Raw264.7 macrophage cell line. METHODS: The M1 polarization of macrophages was induced by lipopolysaccharide and interferon-γ. Interleukin-4 induced M2 polarization and the expression of endogenous miR-378a in each cell type was detected using qRT-PCR to verify whether miR-378a was involved in the polarization of macrophages. By transfection with lentivirus as the vector of overexpression of miR-378a, the stable expression of miR-378a cell lines was screened. Macrophage M1 polarization was induced synergically by lipopolysaccharide and interferon-γ. Macrophage M2 polarization was induced by interleukin-4. The levels of M1/M2 polarizationrelated cytokines in the supernatant of the macrophage culture medium were determined by enzyme-linked immunosorbent assay. qRT-PCR was used to detect the polarization characteristics of M1/M2-type macrophages and the mRNA expression levels of related cytokines. RESULTS AND CONCLUSION: (1) The expression level of endogenous miR-378a in Raw264.7 cells of each group increased after macrophage polarization. (2) Compared with the non-transfected group, the expressions of proinflammatory cytokine-induced nitric oxide synthase, tumor necrosis factor-α, interleukin-6 and interleukin-1β in macrophage M1 induced polarization were significantly decreased in the miR-378a transfection group (P < 0.05); the levels of inducible nitric oxide synthase, tumor necrosis factor-α and interleukin-6 in cell supernatant were also significantly decreased (P < 0.05). (3) Compared with the nontransfected group, the expressions of CD206, interleukin-10 and arginase-I in macrophage M2 induced polarization were significantly increased (P < 0.05); the levels of CD206 and interleukin-10 in cell supernatant were also significantly increased (P < 0.05) in the miR-378a transfection group. (4) It is indicated that overexpression of miR-378a promotes the M2 polarization of macrophages and inhibits the M1 polarization of macrophages. [ABSTRACT FROM AUTHOR]

Purpose: A systematic evaluation and Meta-analysis were performed to determine the relationship between IL-17A levels in ocular aqueous and peripheral venous serum samples and diabetic retinopathy (DR). Methods: PubMed, Embase, Web of Science, and CNKI databases were searched from the time of library construction to 2023-09-20. The results were combined using a random-effects model, sensitivity analyses were performed to determine whether the arithmetic was stable and reliable, and subgroup analyses were used to look for possible sources of heterogeneity. Results: A total of 7 case-control studies were included. The level of IL-17A was higher in the Nonproliferative DR(NPDR) group than in the Non-DR(NDR) group [SMD=2.07,95%CI(0.45,3.68), P=0.01], and the level of IL-17A in the proliferating DR(PDR) group was higher than that of the NDR group [SMD=4.66,95%CI (1.23,8.08),P<0.00001]. IL-17A levels in peripheral serum and atrial fluid were significantly higher in NPDR and PDR patients than in non-DR patients in subgroup analyses, and detection of peripheral serum IL-17A concentrations could help to assess the risk of progression from NPDR to PDR. Sensitivity analyses suggested that the results of the random-effects arithmetic were stable and reliable. Subgroup analyses based on assay method and sample source showed that the choice of these factors would largely influence the relationship between IL-17A levels and DR. Conclusion: Elevated peripheral serum and ocular aqueous humor IL-17A levels in diabetic patients are associated with the risk of DR, IL-17A may serve as a potential predictor or therapeutic target for DR, and IL-17A may be an important predictor of inflammation for the progression of NPDR to PDR. [ABSTRACT FROM AUTHOR]

Objective To investigate the effects of miR-660-3p targeting NFAM1 on the apoptosis and inflammatory factors of human bronchial epithelial cells induced by respiratory syncytial virus （RSV) . Methods Human bronchial epithelial cells 16HBE were cultured in vitro. 16HBE cells in the logarithmic growth phase were randomly divided into the control group, RSV group, miR-660-3p + RSV group, miR-NC + RSV group, pcDNA-NC + RSV group, pcDNA-NFAM1 +RSV group, miR-660-3p + pcDNA-NC + RSV group, and miR-660-3p + pcDNA-NFAM1 + RSV group, respectively. Cells in the miR-NC + RSV group were transfected with NC mimics, miR-660-3p + RSV group with miR-660-3p mimics, pcDNA-NFAM1 + RSV group with pcDNA-NFAM1, pcDNA-NC + RSV group with PCDNA-NFAM1, pcDNA-NC + RSV group with PCDNA-NC, and cells in the miR-660-3p + pcDNA-NC + RSV group were co-transfected with pcDNA-NC and miR-660-3p mimics, and cells in the miR-660-3p + pcDNA-NFAM1 + RSV group were co-transfected with pcDNANFAM1 and miR-660-3p mimics； cells in the control group and RSV group were not transfected. Then, all groups except the control group were infected with RSV and the MOI was set at 0. 000 1. Cells in each group were collected, and the expression levels of miR-660-3p and NFAM1 mRNA were detected by RT-qPCR, apoptosis rate was detected by flow cytometry, and protein expression levels of Cleaved Caspase-3 and NFAM1 were detected by Western blotting； the super⁃ natant of each group was collected, and TNF-α, IL-6 and IL-1β were detected by ELISA； the targeting binding sites of NFAM1 and miR-660-3p were predicted by starBase database, and the targeting regulatory relationship between miR-660-3p and NFAM1 was verified by double luciferase reporter gene assay. Results Compared with the control group, the expres⁃ sion of miR-660-3p decreased, the expression of NFAM1 mRNA and protein and Cleaved Caspase-3 protein increased, the apoptosis rate and the levels of TNF-α, IL-6 and IL-1β in culture supernatance increased in the RSV group （all P<0. 05) . Compared with the miR-NC + RSV group, the expression of miR-660-3p increased, Cleaved Caspase-3 protein expres⁃ sion, apoptosis rate, and levels of TNF-α, IL-6, and IL-1β in the culture supernatance decreased in the miR-660-3p + RSV group （all P<0. 05) . Compared with the pcDNA-NC + RSV group, NFAM1 mRNA, Cleaved Caspase-3 protein expression, apoptosis rate and TNF-α, IL-6 and IL-1β levels in culture supernatance increased in the pcDNA-NFAM1 + RSV group （all P<0. 05) . The starBase database predicted that there was a binding site to miR-660-3p in the 3 'non-coding region of NFAM1. The results of double luciferase reporter gene experiment showed that the luciferase activity of 16HBE cells co-transfected with NC mimics and NFAM1-WT decreased in comparison with that of 16HBE cells co-transfected with miR-660-3p mimics and NFAM1-WT （P<0. 05) . Compared with 16HBE cells co-transfected with NC mimics and NFAM1- MUT, 16HBE cells co-transfected with miR-660-3p mimics and NFAM1-MUT had no significant changes in luciferase activity （P>0. 05) . Compared with the miR-660-3p + pcDNA-NC + RSV group, Cleaved Caspase-3 protein expression, apoptosis rate, and the levels of TNF-α, IL-6, and IL-1β in culture supernatance increased in the miR-660-3p + pcDNANFAM1 + RSV group （all P<0. 05) . Conclusion The miR-660-3p can inhibit RSV-induced apoptosis and secretion of inflammatory factors in human bronchial epithelial cells by targeting and negatively regulating NFAM1. [ABSTRACT FROM AUTHOR]

Background: As inhibitors of 3‐hydroxy‐3‐methylglutaryl‐CoA reductase (HMGCR), statins can reduce the synthesis of low‐density lipoptrotein cholesterol (LDL‐C), and are clinically used as first‐line lipid‐lowering drugs to prevent cardiovascular diseases. However, the effect of statins on sepsis is controversial. Therefore, we intend to explore the effects of statins on sepsis and inflammatory factors through Mendelian randomization (MR). Method: We obtained sepsis, inflammatory factors, and LDL‐C data from open and free genome‐wide association study (GWAS) for subsequent analysis. Inverse‐variance weighted (IVW) was the main method, MR‐Egger, MR‐PRESSO and Cochrane's Q‐test were used as sensitive analysis to evaluate the robustness of MR results. Results: Statins were associated with a reduced risk of sepsis under 75 (sepsis in individuals under 75 years old) (OR:.716, 95% CI:.572–.896, p =.003), elevated circulating IL‐18 (OR:.762, 95% CI:.643–.903, p =.002) and elevated circulating CCL2 (OR:.416, 95% CI:.279–.620, p = 1.685e−5). Conclusion: Statins may have a protective effect on sepsis and this may provide a new idea for the treatment of sepsis. [ABSTRACT FROM AUTHOR]

Objective To explore the efficacy of combination therapy of Ginkgo biloba injection and donepezil in the treatment of Alzheimer's disease (AD) based on cerebral hemodynamics and inflammatory factors. Methods A total of 90 patients with AD in Zhangjiakou Shalingzi Hospital from March 2020 to January 2022 were randomly divided into a control group ( 45 cases) and a study group (45 cases) . Both groups received the conventional symptomatic treatment. On this basis, the control group was given donepezil treatment, and the study group was given ginkgo leaf injection combined with donepezil treatment. The therapeutic effects, cerebral hemodynamic parameters [mean flow velocity (MFV) and pulsatility index (PI) of bilateral middle cerebral arteries (bilateral MCA) and basilar arteries (BA)], inflammatory factors [interleukin-6 (IL-6), tumor necrosis factorα (TNF-α), IL-1β], s100β protein, Aβ-amyloid 1-42 ( Aβ1-42), bradykinin (BK), cognitive function, activities of daily living, and adverse reactions were compared between the two groups. Results Compared with the control group (77.78%), the total effective rate of the study group (93.33%) was significantly improved (P < 0.05); 1, 3, and 6 months after the treatment, the MFV of BA and bilateral MCA in the study group was higher than that in the control group, while the PI of BA and bilateral MCA was lower than that in the control group (P < 0.05); The levels of serum TNF-α, IL-6, and IL-1β in the study group were lower than those in the control group 1, 3, and 6 months after the treatment (P < 0.05); 1, 3, and 6 months after the treatment, the levels of serum s100β protein, Aβ1-42, and BK in the study group were lower than those in the control group（P< 0.05); 1, 3, and 6 months after the treatment, the score of the mini-mental state examination scale (MMSE) in the study group was higher than that in the control group, while the scores of the AD assessment subscale cognitive scale (ADAS-cog) and activities of daily living scale (ADL) were lower than those in the control group (P < 0.05); The incidence of adverse reactions in the study group (13.33%) was not significantly different from that in the control group (8.89%) (P > 0.05). Conclusion The efficacy of ginkgo biloba injection combined with donepezil in the treatment of AD is significant, which may be achieved by improving cerebral hemodynamics, downregulating inflammatory factors, and regulating the levels of serum s100β protein, Aβ1-42, and BK. [ABSTRACT FROM AUTHOR]

Objective To investigate the relationship between type 2 diabetes mellitus (T2DM) combined with sarcopenia and inflammatory markers such as neutrophil count/lymphocyte count (NLR) in the middle-aged and elderly. Methods Two hundred and fifty-one patients with type 2 diabetes mellitus hospitalized in the Department of Endocrinology and Department of Family Medicine of the Affiliated Hospital of North China University of Science and Technology were selected from November 2022 to May 2023. The patients were divided into T2DM group and T2DM combined with myasthenia gravis group. Data on patients' basic conditions and clinical indicators were collected. Inflammatory markers such as NLR were calculated. The relationship between sarcopenia and inflammatory markers such as NLR was analyzed using multifactorial logistic regression. Results Compared to those in the T2DM group, age, leukocyte, uric acid, NLR, and MHR levels were elevated, HDL-C levels decreased, and the difference was statistically significant (P<0.05). The results of multifactorial logistic regression showed that elevated NLR levels and increasing age were independent risk factors for T2DM combined with sarcopenia. The elevated HDL-C level was an independent protective factor for T2DM combined with sarcopenia (P<0.05). ROC curve analysis showed that the AUC of NLR for predicting T2DM combined with sarcopenia in the study population was 0.737 (95% CI: 0.646-0.828). Conclusion In the middle-aged and elderly patients with type 2 diabetes mellitus, elevated NLR level is an independent risk factor for sarcopenia. NLR is valuable in predicting T2DM combined with sarcopenia. [ABSTRACT FROM AUTHOR]

BACKGROUND: Stroke is the second reason for global deaths and a major reason for disabilities. OBJECTIVE: To unravel the clinical value of the coagulation index and serum inflammatory cytokines in hemorrhagic stroke patients with pulmonary infection in the sequelae stage. METHODS: Altogether, 130 hemorrhagic stroke patients who received treatment in Hebei General Hospital from April 2019 to December 2020 were selected. Patients were classified into the infection group (n = 65) and non-infection group (n = 65) according to whether they had a pulmonary infection in the sequelae stage of hemorrhagic stroke. Levels of coagulation index and serum inflammatory cytokines of patients in two groups were compared. Multiple linear regression analysis was used to analyze pulmonary infection-related factors of hemorrhagic stroke patients. The diagnostic value of the coagulation index and serum inflammatory cytokines in pulmonary infection was analyzed by the receiver operating characteristic (ROC) curve. RESULTS: Prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), D-dimer (D-D), platelet (PLT) related to coagulation function levels and interleukin 1 β (IL-1 β), interleukin 17 (IL-17) related to serum inflammatory cytokines levels of patients in the infection group were higher than those in non-infection groups (p < 0.05). Multiple linear regression analysis uncovered that FIB, D-D, PLT, and IL-17 were influencing factors of pulmonary infection in the sequelae of patients with hemorrhagic stroke (p < 0.05). Area under the curve (AUC) values of pulmonary infection in the sequelae stage of patients with hemorrhagic stroke diagnosed by FIB, D-D, PLT, and IL-17 were 0.823, 0.758, 0.660, and 0.755, respectively. CONCLUSION: FIB, D-D, PLT, and IL-17 levels could be used for pulmonary infection diagnosis in the sequelae stage of hemorrhagic stroke patients. [ABSTRACT FROM AUTHOR]

Objective To observe the expression of NOD-like receptor family 3 (NLRP3) protein, interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in the process of gout inflammation induced by macrophage monosodium urate (MSU) crystals in macrophages differentiated from leukemia cells overexpressing purinergic receptor P2X ligand-gated ion channel 7 (P2X7R) . Methods THP-1 cell line were taken and randomly divided into the overexpression group, empty vector group, model group and control group, respectively. Cells in the overexpression group and empty vector group were transfected with P2X7R overexpression plasmid and empty vector plasmid for five days, respectively. THP-1 cells in the vector group, empty vector group and model group were stimulated with 100 ng/mL PMA for three hours and then were differentiated into macrophages. In addition, MSU crystals were dissolved with sodium hydroxide to prepare MSU chyle suspension at a concentration of 100 μg/mL and were incubated in the culture medium for six hours. Cells in the control group were cultured normally. The mRNA and protein of P2X7R in macrophages were measured by RT-PCR and Western blotting, respectively. IL-1β and TNF-α in the supernatant of macrophages were detected by ELISA, and the NLRP3 protein in macrophages was measured by Western blotting. Results Compared with the control group, the relative expression levels of P2X7R mRNA and protein, IL-1β and TNF-α in cell supernatant and NLRP3 protein all increased in the overexpression group, empty vector group and model group (all P<0. 05) . Compared with the model group and empty vector group, the relative expression levels of P2X7R mRNA and protein, IL-1β and TNF-α in cell supernatant and NLRP3 protein all increased in the overexpression group (all P<0. 05) . Conclusion The expression of IL-1β, TNF-α and NLRP3 increases and the levels of IL-1β and TNF-α levels increase in the process of gout inflammation induced by MSU crystals of macrophages differentiated from leukemia cells with P2X7R overexpression, which may be achieved by activating NLRP3 protein. [ABSTRACT FROM AUTHOR]

BACKGROUND: Tabersonine has shown good therapeutic effects in diseases such as myocardial remodeling, acute kidney injury and lung injury due to its an inflammatory biological activity. Prosthetic wear particles often lead to aseptic inflammation, and the massive release of inflammatory factors further promotes periprosthetic bone destruction and bone loss; however, there are no basic studies on the efficacy of tabersonine on periprosthetic osteolysis. OBJECTIVE: To investigate the effects of tabersonine on osteoclast activation, expression of inflammatory factors and inflammatory osteolysis induced by wear particles. METHODS: (1) Cell experiment: RAW264.7 cells were divided into four groups for culture. A complete medium was added in the control group. Osteoclast induction medium (50 ng/mL RANKL+complete medium) was added to the osteoclast induction group. 1 and 5 μmol/L tabersonine was added for 4 hours, and then osteoclast induction medium was added to the low- and high-dose tabersonine groups, respectively. After 5 days of induction, tartrate-resistant acid phosphatase staining, F-actin staining and RT-PCR were performed. (2) Animal experiments: Twenty C57BL/6J mice were randomly divided into sham operation group, osteolysis group, low-dose tabersonine group and high-dose tabersonine group (n=5 per group). Skull osteolysis model of the skull was established by injecting titanium pellets on the skull surface in the osteolysis group, low-dose tabersonine group and high-dose tabersonine group. On day 2 after model establishment, mice in the low-dose and high-dose tabersonine groups received intraperitoneal injections of 10 and 20 mg/kg tabersonine every 2 days, respectively. 2 weeks after surgery, mouse sera were collected for detecting inflammatory factors (interleukin 1β, interleukin 6, and tumor necrosis factor α), and cranial bones were collected for micro-CT scan and bone parameter analysis. RESULTS AND CONCLUSION: (1) Cellular experiments: Tartrate-resistant acid phosphatase staining and F-actin staining showed that compared with the osteoclast induction group, low-dose and high-dose tabersonine significantly inhibited osteoclast activation and bone resorption, and the inhibition was more significant in the high-dose tabersonine group. RT-PCR results showed that compared with the control group, the mRNA expressions of three kinds of inflammatory factors were increased in the osteoclast induction group (P < 0.01). Compared with the osteoclast induction group, the mRNA expressions of three kinds of inflammatory factors were decreased in low- and high-dose tabersonine groups (P < 0.01), and the decrease was more obvious in the highdose tabersonine group. (2) Animal experiments: Compared with the sham operation group, the levels of three kinds of inflammatory factors were increased in the osteolysis group (P < 0.01). Compared with the osteolysis group, the levels of three kinds of inflammatory factors were decreased in the low- and highdose tabersonine groups (P < 0.05, P < 0.01), and the decrease was more obvious in the high-dose tabersonine group. The micro-CT scan results revealed that titanium particles caused the destruction of cranial osteolysis, and tabersonine could inhibit the osteolysis induced by titanium particles, especially in the highdose tabersonine group. (3) The results confirm that tabersonine can enhance the osteolysis and bone destruction induced by titanium particles by inhibiting the release of inflammatory factors and down-regulating the bone absorption function of osteoclasts. [ABSTRACT FROM AUTHOR]

The emergence of multi-drug-resistant (MDR) pathogens has considerably challenged the development of new drugs. Probiotics that inhibit MDR pathogens offer advantages over chemical antibiotics and drugs due to their increased safety and fewer side effects. This study reported that Weissella cibaria P-8 isolated from pickles showed excellent antibacterial activity against intestinal pathogens, particularly the antibacterial activity against MDR Escherichia coli B2 was the highest. This study showed that the survival rates of W. cibaria P-8 at pH 2.0 and 0.3% bile salt concentration were 72% and 71.56%, respectively, and it still had antibacterial activity under pepsin, trypsin, protease K, and catalase hydrolysis. Moreover, W. cibaria P-8 inhibits the expression of inflammatory factors interleukin-1β, tumor necrosis factor-α, and interleukin-6, upregulates the interleukin-10 level, and increases total antioxidant capacity and superoxide dismutase enzyme activity in serum. W. cibaria P-8 also efficiently repairs intestinal damage caused by E. coli infection. The gut microbiota analysis demonstrated that W. cibaria P-8 colonizes the intestine and increases the abundance of some beneficial intestinal microorganisms, particularly Prevotella. In conclusion, W. cibaria P-8 alleviated MDR E. coli-induced intestinal inflammation by regulating inflammatory cytokine and enzyme activity and rebalancing the gut microbiota, which could provide the foundation for subsequent clinical analyses and probiotic product development. [ABSTRACT FROM AUTHOR]

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There is still a lack of high-level evidence regarding the causal relationship between smoking and intervertebral disc degenerative diseases. This study utilized data from genome wide analysis studies and conducted two-sample Mendelian randomization analyses across multiple heterogeneous datasets. We evaluated the causal relationships between smoking behavior, serum inflammatory factors, serum chemokines, and intervertebral disc degeneration. Sensitivity analysis was performed to examine data heterogeneity and the pleiotropy of causal effects. The results indicated that smokers were liable to develop intervertebral disc degeneration (OR 1.770; 95 % CI, 1.519–2.064; p = 2.992 × 10–13), and long-term smoking behavior increased the risk of intervertebral disc degeneration (OR 1.715; 95 % CI 1.475–1.994; P = 2.220 × 10–12). Additionally, a causal relationship was confirmed between serum IL-1β level and intervertebral disc degeneration (OR 1.087; 95 % CI, 1.023–1.154; p = 0.007). The “smoking index” representing lifelong smoking habit was also found to be causally related to serum MCP-3 level(β = 0.292; SE = 0.093; p = 0.002). All of the causality mentioned above remained stable in sensitivity tests. Based on the analysis results and fundamental medicine theories around macrophage-induced inflammation in degenerative intervertebral discs, we have constructed a new mechanism that long-term smoking could induce an increase in serum MCP-3 level, promoting the gathering and activation of monocyte macrophages. Furthermore, the recruited macrophages led to an increase in local IL-1β within the intervertebral disc, ultimately exacerbating the process of intervertebral disc degeneration. What we have found is expected to accelerate the development of prevention and treatment of intervertebral disc degeneration.

Abstract Background The current study was conducted aimed atexploring the effects of staged rehabilitation training on the levels of inflammatory factors and red blood cell distribution in patients who underwent cardiac valve replacement. Methods A total of 140 patients who underwent cardiac valve replacement at The First Hospital of Hebei Medical University between April 2021 and November 2022 were included in this study. During the postoperative rehabilitation phase, the patients were randomly assigned to either the control group or the experimental group. The experimental group received staged rehabilitation training (n = 70), while the control group received conventional care and rehabilitation suggestions without specialized staged rehabilitation training (n = 70). Informed consent was obtained from all patients prior to theirinclusion in the study. Clinical data of the patients were collected andanalyzed. RDW was measured using an automated blood cell analyzer on postoperative day 1, 14, and 28. Levels ofTNF-α, IL-6 and CRP were measured using ELISA. Quality of life was evaluated usingthe WHOQOL-BREF questionnaire. The effects of postoperative rehabilitation were assessed using the 6MWD test. The occurrence of adverse events in the postoperative periodwas alsoanalyzed. Results There were no significant differences in the general characteristics of the two groups of patients (P > 0.05). On the first day after surgery, no significant differences were seen in RDW between the two groups (P > 0.05). However, on the 14th and 28th day after surgery, the experimental group exhibited a significant reduction in RDW compared to the control group (P 0.05). However, on the 14th and the 28th after surgery, the experimental group showed evidently lower levels of TNF-α, IL-6 and CRP compared to the control group (P 0.05). Conclusion Staged rehabilitation training exerteda positive effect on the levels of inflammatory factors and red blood cell distribution in patients following cardiac valve replacement. This type of rehabilitation training facilitated the patient’s recovery process by reducing the inflammatory response and improving the condition of red blood cells. Additionally, it enhanced the quality of life and rehabilitation outcomes for patients.

Psoriasis is accepted as a chronic, inflammatory, immune-mediated skin disease triggered by complex environmental and genetic factors. For a long time, disease recurrence, drug rejection, and high treatment costs have remained enormous challenges and burdens to patients and clinicians. Natural products with effective immunomodulatory and anti-inflammatory activities from medicinal plants have the potential to combat psoriasis and complications. Herein, an imiquimod (IMQ)-induced psoriasis-like dermatitis model is established in mice. The model mice are treated with 1% rutaecarpine (RUT) (external use) or the oral administration of RUT at different concentrations. Furthermore, high-throughput 16S rRNA gene sequencing is applied to analyze the changes in the diversity and composition of the gut microbiota. Based on the observation of mouse dorsal skin changes, RUT can protect against inflammation to improve psoriasis-like skin damage in mice. Additionally, RUT could suppress the expression levels of proinflammatory cytokines (IL-23, IL-17A, IL-22, IL-6, and IFN-α) within skin tissue samples. Concerning gut microbiota, we find obvious variations within the composition of gut microflora between IMQ-induced psoriasis mice and RUT-treated psoriasis mice. RUT effectively mediates the recovery of gut microbiota in mice induced by IMQ application. Psoriasis is linked to the production of several inflammatory cytokines and gut microbiome alterations. This research shows that RUT might restore gut microbiota homeostasis, reduce inflammatory cytokine production, and ameliorate psoriasis symptoms. In conclusion, the gut microbiota might be a therapeutic target or biomarker for psoriasis that aids in clinical diagnosis and therapy.

Abstract Objective To explore the mechanism of huankuile (HKL) in colon injury repair in rats with ulcerative colitis (UC). Methods Fifty SPF Wistar male rats were divided randomly into a normal group, a negative control group, an HKL intervention group (‘HKL group’) and a 5-aminosalicylic acid intervention group (‘5-ASA group’). After 14 days of intervention with corresponding drugs, pathological scores were obtained using the results of immunohistochemical staining; morphological changes were observed by hematoxylin–eosin staining, and the mRNA expression levels of tumour necrosis factor-α (TNF-α), matrix metalloproteinase 9 (MMP9) and interleukin-13 (IL-13) were detected by real-time quantitative PCR. Results After the successful construction of the rat model, it was compared with the rats in the normal group. In the negative group, it was found that the expression of TNF-α and MMP9 was significantly increased in the colonic mucosal epithelia of the rats, the pathological score was significantly increased (P

Objective: To research the therapeutic effects and mechanisms of ligustilide (Lig) in improving dextran sodium sulfate (DSS)-induced ulcerative colitis (UC) in mice. Methods: Intervention of lig was delivered in sixty male SPF C57 BL/6 mice and the mice were differentiated in six groups according to the dose of lig as: Control group, DSS group, positive control group (treated with sulfasalazine, SASP), low-dose lig group, medium-dose lig group, and high-dose lig group. The UC in DSS mice was induced by a 3% DSS solution through oral administration for 7 days, in the meanwhile, the low, medium, and high-dose lig groups were received gavage feeding of lig and oral administration of 3% DSS solution. Before and after the intervention, the body weight, colon length, and the disease activity index (DAI) score were collected for assessment of UC. Furthermore, the expression levels of TLR4/NF-κB proteins in colon and serum TNF-α, IL-6, and IL-1β were quantitatively measured using enzyme-linked immunosorbent (ELISA) assays. Additionally, histological examination was performed to investigate the effects and mechanisms of lig in improving UC in mice by hematoxylin-eosin staining. Results: Compared to the control group, significantly reduced body weight (P

In order to investigate the pharmacological effect of Paeonia suffruticosa Andr. stamens on chronic non-bacterial prostatitis (CNBP) in rats, the rats with chronic abacterial prostatitis induced by castration combined subcutaneous injection of hormone (estradiol benzoate 0.25 mg·kg−1) were used as models. Forty rats with CNBP were randomly divided into five groups (8 per group): Model group (normal saline), positive group (celecoxib 250 mg·kg−1), various doses of lyophilized powder of Paeonia suffruticosa Andr. stamens groups (100, 200, 400 mg·kg−1). Another group of normal mice treated with normal saline as normal group. The therapeutic effect of Paeonia suffruticosa Andr. stamens on CNBP was evaluated by lecithin body density, prostatic index, cytokines in prostate tissue and the expression levels of TXB2 and 6-K-PGF1α in blood. The results showed that the inflammation of prostate tissue in rats was significantly improved. Compared with model group, the number of white blood cells, prostate weight, prostate index, TXB2 and the content of PGE2 in prostate tissue of rats were significantly decreased in each dosage group of Paeonia suffruticosa Andr. stamens (P0.05). The contents of 6-keto-PGF1α and NO in high dose of Paeonia suffruticosa Andr. stamens were significantly increased (P0.05). This study showed that Paeonia suffruticosa Andr. stamens had therapeutic effect on chronic abacterial prostatitis, which would provide a theoretical basis for further development and application of the Paeonia suffruticosa Andr. stamens.