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BACKGROUND: The rapid increase in the number of patients with chronic diseases and depression, as well as the rapid spread of their effects, have led to these two health problems gradually developing into major public health issues in China and around the world. Currently, many individuals with chronic diseases are experiencing depressive symptoms one after another. Therefore, it is imperative to conduct research on how to prevent depression in this growing population of individuals with chronic diseases in a timely manner. METHODS: Based on the data of the 2015 and 2018 national follow-up surveys of the China Health and Elderly Care Longitudinal Survey, a total of 7641 patients with short-term increase in the number of chronic diseases were selected as the study objects, and a binary logistic regression model was constructed according to the five dimensions of the health ecology model. The neural network model was used to explore the main (first two) factors affecting the increase in the number of chronic diseases in China in the short term, and the random forest and extreme value gradient lifting algorithm were used to verify them, and effective suggestions were put forward. RESULTS: The detection rate of depression in the population with increasing number of chronic diseases from 2015 to 2018 was 42.13 %. The model was established based on five dimensions of the health ecology model: Model 1 (Personal trait layer), Model 2 (Personal trait layer plus Behavioral feature layer), Model 3 (Personal trait layer plus Behavioral feature layer plus Living and working conditions layer), Model 4 (Personal trait layer plus Behavioral feature layer plus Living and working conditions layer plus Networking layer) and Model 5 (Personal trait layer plus Behavioral feature layer plus Living and working conditions layer plus Networking layer plus Policy environment layer).The prediction accuracy of the five models was 66.4 %, 68.3 %, 70.7 %, 71.6 % and 71.6 %, respectively, and Model 5 showed that the P values of gender, self-rated health, night's sleep time (h), disability, life satisfaction, child satisfaction, place of residence and highest level of education were all <0.05, life satisfaction and self-rated health importance were 0.249 (100 %) and 0.226 (90.8 %). CONCLUSION: Gender, self-rated health, night sleep duration, disability, satisfaction with life, satisfaction with children, place of residence and highest level of education were the main influencing factors for the increase of depressive symptoms in the population with chronic diseases in the short term, among which life satisfaction and self-rated health have the greatest impact on depressive symptoms, and there is an interaction between the two.

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Objective To explore the relationship between the expression levels of microRNA-155 (miR-155) and suppressor of cytokine signaling 1 (SOCS1) in the colonic mucosal tissue of patients with ulcerative colitis (UC) and the severity of the disease.Methods A total of 130 UC patients admitted to the Second Affiliated Hospital of Hebei North University from September 2021 to June 2023 were selected.According to the modified Mayo score system,the patients were assigned into an active stage group (n=85) and a remission stage group (n=45).According to the modified Truelove and Witts classification criteria,the UC patients at the active stage were assigned into a mild group (n=35),a moderate group (n=30),and a severe group (n=20).A total of 90 healthy individuals who underwent colonoscopy for physical examination or those who had normal colonoscopy results after single polypectomy and excluded other diseases were selected as the control group.The colonic mucosal tissues of UC patients with obvious lesions and the colonic mucosal tissue 20 cm away from the anus of the control group were collected.The levels of miR-155 and SOCS1 mRNA in tissues were determined by fluorescence quantitative PCR,and the expression of SOCS1 protein in tissues was determined by immunohistochemistry.The correlations of the levels of miR-155 and SOCS1 mRNA in the colonic mucosal tissue with the modified Mayo score of UC patients were analyzed.The values of the levels of miR-155 and SOCS1 mRNA in predicting the occurrence of severe illness in the UC patients at the active stage were evaluated.Results Compared with the control group and the remission stage group,the active stage group showed up-regulated expression level of miR-155,down-regulated level of SOCS1 mRNA,and decreased positive rate of SOCS1 protein in the colonic mucosal tissue (all P<0.001).The expression level of miR-155 and modified Mayo score in colonic mucosal tissues of UC patients at the active stage increased,while the mRNA level of SOCS1 was down-regulated as the disease evolved from being mild to severe (all P<0.001).The modified Mayo score was positively correlated with the miR-155 level and negative correlated with the mRNA level of SOCS1 in colonic mucosal tissues of UC patients (all P<0.001).The high miR-155 level (OR=2.762,95%CI=1.284-5.944,P=0.009),low mRNA level of SOCS1 (OR=2.617,95%CI=1.302-5.258,P=0.007),and modified Mayo score≥12 points (OR=3.232,95%CI=1.450-7.204,P=0.004) were all risk factors for severe disease in the UC patients at the active stage.The area under curve of miR-155 combined with SOCS1 mRNA in predicting severe illness in the UC patients at the active stage was 0.920.Conclusions The expression levels of miR-155 and SOCS1 mRNA were correlated with the disease severity in the UC patients at the active stage.The combination of the two indicators demonstrates good performance in predicting the occurrence of severe illness in UC patients at the active stage.

Asunto(s)

Colitis Ulcerosa , Mucosa Intestinal , MicroARNs , Proteína 1 Supresora de la Señalización de Citocinas , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Colitis Ulcerosa/genética , Colitis Ulcerosa/metabolismo , Colitis Ulcerosa/patología , Colitis Ulcerosa/fisiopatología , Colon/metabolismo , Colon/patología , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , MicroARNs/genética , MicroARNs/metabolismo , Índice de Severidad de la Enfermedad , Proteína 1 Supresora de la Señalización de Citocinas/genética , Proteína 1 Supresora de la Señalización de Citocinas/metabolismo

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The latest research indicates that modulating microglial polarization from M1 to M2 phenotype may be a coping therapy for ischemic stroke. The present study thereby evaluated the effects of loureirin B (LB), a monomer compound extracted from Sanguis Draconis flavones (SDF), on cerebral ischemic injury and the potential mechanisms. The middle cerebral artery occlusion (MCAO) model was established in male Sprague-Dawley rats to induce cerebral ischemia/reperfusion (I/R) injury in vivo, and BV2 cells were exposed to oxygen-glucose deprivation and reintroduction (OGD/R) to mimic cerebral I/R injury in vitro. The results showed that LB significantly reduced infarct volume, neurological deficits and neurobehavioral deficits, apparently improved histopathological changes and neuronal loss in cortex and hippocampus of MCAO/R rats, markedly decreased the proportion of M1 microglia cells and the level of pro-inflammatory cytokines, and increased the proportion of M2 microglia and the level of anti-inflammatory cytokines both in vivo and in vitro. In addition, LB evidently improved the p-STAT6 expression and reduced the NF-κB (p-p65) expression after cerebral I/R injury in vivo and in vitro. IL-4 (a STAT6 agonist) exhibited a similar impact to that of LB, while AS1517499 (a STAT6 inhibitor) significantly reversed the effect of LB on BV-2 cells after OGD/R. These findings point to the protection of LB against cerebral I/R injury by modulating M1/M2 polarization of microglia via the STAT6/NF-κB signaling pathway, hence LB may be a viable treatment option for ischemic stroke.

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Lesiones Encefálicas , Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Daño por Reperfusión , Ratas , Masculino , Animales , FN-kappa B/metabolismo , Microglía , Ratas Sprague-Dawley , Transducción de Señal , Infarto de la Arteria Cerebral Media/complicaciones , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Infarto de la Arteria Cerebral Media/metabolismo , Lesiones Encefálicas/metabolismo , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/prevención & control , Daño por Reperfusión/metabolismo , Accidente Cerebrovascular Isquémico/metabolismo , Citocinas/metabolismo , Isquemia Encefálica/metabolismo

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Many studies have shown a close association between Nogo-B and inflammation-related diseases. However, uncertainty does exist, regarding Nogo-B function in the pathological progression of cerebral ischemia/reperfusion (I/R) injury. Middle cerebral artery occlusion/reperfusion (MCAO/R) model was utilized in C57BL/6L mice to mimic ischemic stroke in vivo. Using oxygen-glucose deprivation and reoxygenation (ODG/R) model in microglia cells (BV-2) to establish cerebral I/R injury in vitro. Various methods, including Nogo-B siRNA transfection, mNSS and the rotarod test, TTC, HE and Nissl staining, immunofluorescence staining, immunohistochemistry, Western blot, ELISA, TUNEL and qRT-PCR were employed to probe into the effect of Nogo-B downregulation on cerebral I/R injury and the potential mechanisms. A small amount of Nogo-B expression (protein and mRNA) was observed in cortex and hippocampus before ischemia, then Nogo-B expression increased significantly on day 1, reaching the maximum on day 3, remaining stable on day 14 after I/R, and decreasing gradually after 21 days, but it still rose significantly compared with that observed preischemia. Nogo-B down-regulation could markedly reduce the neurological score and infarct volume, improve the histopathological changes and neuronal apoptosis, lower the number of CD86+/Iba1+ cells and the levels of IL-1ß, IL-6, and TNF-α, and raise the density of NeuN fluorescence, the number of CD206+/Iba1+ cells, and the level of IL-4, IL-10 and TGF-ß in brain of MCAO/R mice. Treatment with Nogo-B siRNA or TAK-242 in BV-2 cells could obviously decrease the CD86 fluorescence density and the mRNA expression of IL-1ß, IL-6 and TNF-α, increase CD206 fluorescence density and the mRNA expression of IL-10 after OGD/R injury. In addition, the expression of TLR4, p-IκBα and p-p65 proteins significantly increased in the brain after MCAO/R and BV-2 cells exposed to OGD/R. Treatment with Nogo-B siRNA or TAK-242 prominently reduced the expression of TLR4, p-IκBα and p-p65. Our findings suggest that the down-regulation of Nogo-B exerts protective effect on cerebral I/R injury by modulating the microglia polarization through inhibiting TLR4/NF-κB signaling pathway. Nogo-B may be a potential therapeutic target for ischemic stroke.

Asunto(s)

Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Daño por Reperfusión , Animales , Ratones , Isquemia Encefálica/metabolismo , Regulación hacia Abajo , Infarto de la Arteria Cerebral Media/metabolismo , Interleucina-10/genética , Interleucina-10/metabolismo , Interleucina-10/farmacología , Interleucina-6/metabolismo , Accidente Cerebrovascular Isquémico/metabolismo , Ratones Endogámicos C57BL , Microglía/metabolismo , FN-kappa B/metabolismo , Inhibidor NF-kappaB alfa/genética , Inhibidor NF-kappaB alfa/metabolismo , Inhibidor NF-kappaB alfa/farmacología , Daño por Reperfusión/metabolismo , ARN Mensajero/metabolismo , ARN Interferente Pequeño/farmacología , Receptor Toll-Like 4/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo

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Recent evidence suggests that Nod-like receptor protein-3 (NLRP3) inflammasome is a key mediator of inflammatory response and can induce the activation of apoptosis signaling pathways in ischemic stroke. In this research, we assessed the effects of anfibatide (ANF) on inflammatory and apoptosis in cerebral ischemic injury and the potential mechanisms. Middle cerebral artery occlusion (MCAO) model was established on male Sprague-Dawley rats to induce cerebral ischemia/reperfusion (I/R) injury in vivo. Primary cortical neurons (PCN) cells were exposed to oxygen-glucose deprivation and reintroduction (OGD/R) to mimic cerebral I/R injury in vitro. The results showed that ANF markedly alleviated infarct volume, neurological deficit and neurobehavioral impairment in MCAO/R rats, enhanced cell viability and decreased LDH release in PCN after OGD/R. The number of TUNEL-positive cells, Bax, cleaved-caspase-3, p-IκBα, p-p65, NLRP3, ASC, cleaved caspase-1, IL-ß and IL-18 proteins expression were significantly upregulated in the cortex of MCAO/R rats and PCN exposed to OGD/R, NLRP3 and caspase-1 mRNA levels were also evidently elevated. Bcl-2 protein expression significantly decreased in the cortex of MCAO/R rats. Treatment with ANF obviously inhibited the expression of p-IκBα, p-p65, NLRP3, ASC, cleaved caspase-1, Bax and cleaved-caspase-3, promoted the expression of Bcl-2, then decreased the TUNEL-positive cell number and the level of inflammatory cytokines (IL-ß and IL-18) in cerebral ischemia reperfusion in vito and in vitro. Our findings suggest that ANF exerts effects of alleviating inflammation and apoptosis through inhibiting NF-kappaB/NLRP3 axis. ANF is a potential candidate for treating cerebral I/R injury.

Asunto(s)

Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Daño por Reperfusión , Animales , Masculino , Ratas , Apoptosis , Proteína X Asociada a bcl-2 , Isquemia Encefálica/complicaciones , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/metabolismo , Caspasa 3 , Venenos de Crotálidos , Infarto de la Arteria Cerebral Media/complicaciones , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Infarto de la Arteria Cerebral Media/metabolismo , Inflamación/tratamiento farmacológico , Interleucina-18 , Lectinas Tipo C , FN-kappa B/metabolismo , Inhibidor NF-kappaB alfa , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteínas NLR , Proteínas Proto-Oncogénicas c-bcl-2 , Ratas Sprague-Dawley , Daño por Reperfusión/complicaciones , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/metabolismo

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CONTEXT: Qingluoyin (QLY) is a traditional Chinese medicine (TCM) formula which has been used in treating human rheumatoid arthritis (RA) for years in China. OBJECTIVE: This study investigates the effect of QLY granules on adjuvant arthritis (AA) and the possible mechanism. MATERIALS AND METHODS: Sprague-Dawley (SD) rats were injected with Complete Freund's adjuvant (CFA) to induce the AA model. After the onset of arthritis, rats received intragastric administrations of the QLY granules (1.35, 2.70, and 5.40 g/kg) or Tripterygium glycosides (TG) tablets (positive drug, 10 mg/kg) for 14 d. After 28 d immunization, the symptoms, inflammatory parameters and molecular mechanisms were investigated. RESULTS: In the QLY granule (1.35, 2.70, and 5.40 g/kg) therapy groups, the arthritis index decreased to 6.30 ± 2.06, 5.80 ± 1.55, 5.30 ± 1.16 compared with the model (9.00 ± 3.01), paw swelling decreased to 1.56 ± 0.40, 1.28 ± 0.38, 1.12 ± 0.41 mL compared with the model (2.22 ± 0.73 mL). QLY granules (1.35, 2.70 and 5.40 g/kg) significantly reduced the thymus and the spleen indexes, inhibited the production of pro-inflammatory cytokines, and alleviated the pathological changes of joints compared with the model group. Furthermore, the treatment of QLY granules (2.70 and 5.40 g/kg) markedly inhibited CXCL12, CXCR4 (in spleen and synovium) and p-NF-κB p65 (in synovium) protein expression of AA rats. CONCLUSIONS: QLY granules have obvious therapeutic effects on AA rats, which may be associated with downregulating the CXCL12/CXCR4-NF-κB signalling pathway. QLY granules can be used as a candidate for the treatment of RA, which deserves further study.

Asunto(s)

Artritis Experimental/tratamiento farmacológico , Artritis Reumatoide/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Glicósidos/farmacología , Animales , Artritis Experimental/patología , Artritis Reumatoide/patología , Quimiocina CXCL12/metabolismo , Citocinas/metabolismo , Relación Dosis-Respuesta a Droga , Regulación hacia Abajo , Medicamentos Herbarios Chinos/administración & dosificación , Adyuvante de Freund , Glicósidos/aislamiento & purificación , Masculino , FN-kappa B/metabolismo , Ratas , Ratas Sprague-Dawley , Receptores CXCR4/metabolismo , Transducción de Señal/efectos de los fármacos , Tripterygium/química

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OBJECTIVES: Antinuclear antibody (ANA) positivity is a key finding in JIA-associated uveitis (JIAU), but there are quite a few patients with negative ANA. There is no relevant report on the difference of their clinical manifestations. Previous animal model studies have found that the occurrence of uveitis is related to macrophage activation. In this article, our goal is to investigate changes in the morphology and cytokines of peripheral blood mononuclear cells (PBMCs) in uveitis patients testing positive or negative for ANAs after lipopolysaccharide (LPS) stimulation. METHODS: A total of 30 patients were included in this study (10 in each group). They were divided into three groups (the ANA-positive [ANA+] group, ANA-negative [ANA-] group, and control group). There were ten patients (6 females and 4 males) in each group. Peripheral venous blood was collected into a heparinized tube, and PBMCs were isolated as soon as possible by the Ficoll-Hypaque density gradient separation method. Isolated cells were mixed with RPMI-1640 medium, and the cell concentration was adjusted to ensure that each patient had the same number of cells entering the study. After putting the extracted PBMC into the culture plate, LPS was added carefully to the plate. The cell culture supernatants were collected at 0 h, 3 h, 6 h, 12 h, and 24 h after LPS stimulation to detect the concentrations of IL-6, IL-1, TNF-α, and IL-10. Immunofluorescence was used to discover the deformation of macrophages after LPS stimulation. RESULTS: The newly isolated cells were approximately round. 6 h after LPS stimulation, the ratio of noncircular cells/circular cells was the highest in the ANA+ group. Unlike IL-10 that has been rising during the observation period, IL-6, IL-1, and TNF-α peaked at 6 h after LPS stimulation. CONCLUSION: With LPS motivation, cytokines in the ANA+ group increased the most violently.

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Anticuerpos Antinucleares/sangre , Artritis Juvenil/complicaciones , Citocinas/metabolismo , Leucocitos Mononucleares/inmunología , Uveítis/inmunología , Adolescente , Artritis Juvenil/sangre , Artritis Juvenil/inmunología , Células Cultivadas , Niño , Preescolar , Femenino , Humanos , Leucocitos Mononucleares/metabolismo , Lipopolisacáridos/inmunología , Masculino , Cultivo Primario de Células , Uveítis/sangre , Uveítis/diagnóstico

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The disruption of the blood-brain barrier (BBB) and the consequent brain edema are major contributors to the pathogenesis of cerebral ischemia/reperfusion injury. RhoA is generally thought to play a crucial role in the process of BBB disruption and participate in the signaling pathways emanating from TLR4. However, it remains unverified the regulatory role of TLR4 in the RhoA/ROCK pathway in cerebral I/R injury and its effects on the BBB as well. The present study probes into the protective effect of ANF on the BBB after cerebral I/R injury and the possible mechanisms. Focal cerebral ischemia was induced by 120 min of transient middle cerebral artery occlusion (MCAO). ANF (1, 2, 4 µg/kg) was achieved by intravenous injection after 120 min of MCAO followed by 1, 24, 48, and 72 h reperfusion. Evans blue extravasation, brain water content, RhoA activity, and the expressions of TLR4, ROCK1/2, p-MLC2, MMP-2/9, ZO-1, occludin, and claudin-5 protein in rat brain were evaluated 72 h after reperfusion. ANF could significantly reduce the Evans blue extravasation and water content in the ipsilateral hemisphere and obviously increase the occludin, claudin-5, and ZO-1 expression after cerebral I/R injury. Furthermore, cerebral I/R injury induced apparently increased expression of TLR4, RhoA-GTP, ROCK1/2, p-MLC2, and MMMP-2/9, which, however, could be remarkably alleviated by ANF intervention. Taken together, the TLR4/RhoA/ROCK signaling pathway is implicated in BBB breakdown after cerebral I/R injury, and ANF preserves BBB integrity, probably via inhibiting the TLR4/RhoA/ROCK signaling pathway.

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Barrera Hematoencefálica/efectos de los fármacos , Venenos de Crotálidos/uso terapéutico , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Lectinas Tipo C/uso terapéutico , Fármacos Neuroprotectores/uso terapéutico , Daño por Reperfusión/tratamiento farmacológico , Receptor Toll-Like 4/metabolismo , Animales , Barrera Hematoencefálica/metabolismo , Miosinas Cardíacas/metabolismo , Venenos de Crotálidos/administración & dosificación , Venenos de Crotálidos/farmacología , Lectinas Tipo C/administración & dosificación , Masculino , Metaloproteinasas de la Matriz/metabolismo , Cadenas Ligeras de Miosina/metabolismo , Fármacos Neuroprotectores/efectos adversos , Fármacos Neuroprotectores/farmacología , Ratas , Ratas Sprague-Dawley , Transducción de Señal , Proteínas de Unión al GTP rho/metabolismo , Quinasas Asociadas a rho/metabolismo

RESUMEN

OBJECTIVE: To investigate the protective effect of Wuziyanzong Pills (WYP) in the rat model of oligoasthenospermia (OAS) and its action mechanism. METHODS: Sixty male SD rats were equally randomized into six groups: normal control, OAS model, Shengjing Capsules (1.6 g per kg of the body weight), low-dose WYP (1 g per kg of the body weight), medium-dose WYP (2 g per kg of the body weight), and high-dose WYP (4 g per kg of the body weight). The OAS model was established by intragastric administration of Tripterygium glucoside at 30 mg per g per d for 6 weeks. From the 3rd week of modeling, the rats of the medication groups were treated intragastrically with corresponding drugs for 4 weeks. Then all the rats were sacrificed for measurement of the testicular and epididymal organ coefficients, examination of epididymal sperm quality and apoptosis, and detection of the openness of the sperm mitochondrial permeability transition pore (MPTP). Histopathological changes in the testis were observed by HE staining and the apoptosis of spermatogenic cells determined by Hochest staining. RESULTS: WYP obviously improved the organ coefficients of the testis and epididymis, increased sperm concentration, motility and viability, decreased the apoptosis of spermatogenic cells, and inhibited the abnormal openness of MPTP in the OAS model rats. HE staining showed that the number and levels of spermatogenic cells were significantly increased while Hochest staining manifested that the apoptosis of spermatogenic cells was remarkably inhibited in the seminiferous tubules of the testis in the WYP-treated rats. CONCLUSIONS: WYP can improve sperm quality and reduce the apoptosis of spermatogenic cells (including sperm) in OAS model rats, which may be related with its inhibitory effect on the abnormal openness of MPTP.

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Astenozoospermia/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Epidídimo/efectos de los fármacos , Oligospermia/tratamiento farmacológico , Espermatozoides/efectos de los fármacos , Testículo/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Astenozoospermia/inducido químicamente , Masculino , Proteínas de Transporte de Membrana Mitocondrial/efectos de los fármacos , Poro de Transición de la Permeabilidad Mitocondrial , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Recuento de Espermatozoides , Motilidad Espermática/efectos de los fármacos , Espermatozoides/citología , Tripterygium