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To explore the mechanism of tripartite motif 52 (TRIM52) in the progression of temporomandibular joint osteoarthritis (TMJOA). Gene and protein expression were tested by quantitative real-time polymerase chain reaction and western blot, respectively. The levels of pro-inflammatory cytokines and oxidative stress factors were evaluated using enzyme-linked immunosorbent assay and biochemical kit, respectively. Cell counting kit-8 and 5-ethynyl-2'-deoxyuridine assays were carried out to assess cell proliferation. Immunofluorescence was used to detect the expression of CD68 and Vimentin in primary synovial fibroblasts (SFs). Haematoxylin and eosin staining and Safranin O/Fast green were used to evaluate the pathological damage of synovial and cartilage tissue in rats. TRIM52 was upregulated in the synovial tissue and SFs in patients with TMJOA. Interleukin (IL)-1ß treatment upregulated TRIM52 expression in TMJOA SFs and normal SF (NSF), promoting cell proliferation, inflammatory response and oxidative stress in NSF, SFs. Silence of TRIM52 relieved the cell proliferation, inflammatory response and oxidative stress induced by IL-1ß in SFs, while overexpression of TRIM52 enhanced IL-1ß induction. Meanwhile, IL-1ß induction activated toll-like receptor 4 (TLR4)/nuclear factor (NF)-κB pathway, which was augmented by upregulation of TRIM52 in NSF, and was attenuated by TRIM52 knockdown in SFs. Besides, pyrrolidinedithiocarbamic acid ameliorated IL-1ß-induced proliferation and inflammatory response by inhibiting TLR4/NF-κB signalling. Meanwhile, TRIM52 knockdown inhibited cell proliferation, oxidative stress and inflammatory response in IL-1ß-induced SFs through downregulation of TLR4. TRIM52 promoted cell proliferation, inflammatory response, and oxidative stress in IL-1ß-induced SFs. The above functions were mediated by the activation of TLR4/NF- κB signal pathway.
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Osteoartrite , Receptor 4 Toll-Like , Animais , Humanos , Ratos , Proliferação de Células , Fibroblastos/metabolismo , Interleucina-1beta/metabolismo , NF-kappa B/metabolismo , Osteoartrite/genética , Osteoartrite/metabolismo , Estresse Oxidativo , Articulação Temporomandibular/metabolismo , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismoRESUMO
BACKGROUND: Energy balance is closely related to reproductive function, wherein hypothalamic kisspeptin mediates regulation of the energy balance. However, the central mechanism of kisspeptin in the regulation of male reproductive function under different energy balance states is unclear. Here, high-fat diet (HFD) and exercise were used to change the energy balance to explore the role of leptin and inflammation in the regulation of kisspeptin and the hypothalamic-pituitary-testis (HPT) axis. METHODS: Four-week-old male C57BL/6 J mice were randomly assigned to a normal control group (n = 16) or an HFD (n = 49) group. After 10 weeks of HFD feeding, obese mice were randomly divided into obesity control (n = 16), obesity moderate-load exercise (n = 16), or obesity high-load exercise (n = 17) groups. The obesity moderate-load exercise and obesity high-load exercise groups performed exercise (swimming) for 120 min/day and 120 min × 2 times/day (6 h interval), 5 days/week for 8 weeks, respectively. RESULTS: Compared to the mice in the normal group, in obese mice, the mRNA and protein expression of the leptin receptor, kiss, interleukin-10 (IL-10), and gonadotropin-releasing hormone (GnRH) decreased in the hypothalamus; serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone levels and sperm quality decreased; and serum leptin, estradiol, and tumor necrosis factor-α (TNF-α) levels and sperm apoptosis increased. Moderate- and high-load exercise effectively reduced body fat and serum leptin levels but had the opposite effects on the hypothalamus and serum IL-10 and TNF-α levels. Moderate-load exercise had anti-inflammatory effects accompanied by increased mRNA and protein expression of kiss and GnRH in the hypothalamus and increased serum FSH, LH, and testosterone levels and improved sperm quality. High-load exercise also promoted inflammation, with no significant effect on the mRNA and protein expression of kiss and GnRH in the hypothalamus, serum sex hormone level, or sperm quality. Moderate-load exercise improved leptin resistance and inflammation and reduced the inhibition of kisspeptin and the HPT axis in obese mice. The inflammatory response induced by high-load exercise may counteract the positive effect of improving leptin resistance on kisspeptin and HPT. CONCLUSION: During changes in energy balance, leptin and inflammation jointly regulate kisspeptin expression on the HPT axis.
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Metabolismo Energético/fisiologia , Mediadores da Inflamação/fisiologia , Kisspeptinas/metabolismo , Leptina/fisiologia , Reprodução/fisiologia , Animais , Hipogonadismo/sangue , Hipogonadismo/complicações , Hipotálamo/metabolismo , Infertilidade Masculina/sangue , Infertilidade Masculina/etiologia , Inflamação/sangue , Inflamação/complicações , Mediadores da Inflamação/sangue , Kisspeptinas/fisiologia , Leptina/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Transdução de Sinais/fisiologiaRESUMO
OBJECTIVE: To investigate the effect and action mechanism of Yu Si Granules (YSG) in the treatment methyl methanesulphonate (MMS)-induced oligoasthenozoospermia (OAZ) in mice. METHODS: Thirty adult male mice were randomly divided into three groups of equal number, normal control, OAZ model control and YSG intervention. The OAZ model was established by oral administration of MMS and the model mice in the YSG intervention group were treated intragastrically with YSG suspension at 0.144 g/100 g of the body weight per day for 48 successive days. Then, all the mice were sacrificed and their epididymides harvested for detection of the sperm count and motility, observation of the morphology of the seminiferous tubules by HE staining, determination of the expressions of the germ cell-, sperm cell-, spermatocyte-, Sertoli cell- and blood-testis barrier-related genes by RT-PCR, and measurement of the levels of oxidative stress in the blood. RESULTS: Compared with the normal control, the OAZ model mice showed significantly decreased sperm count (ï¼»49.2 ± 0.7ï¼½ vs ï¼»23.6 ± 0.4ï¼½ ×107/ml/g, P < 0.05) and sperm motility (ï¼»76.3 ± 0.7ï¼½% vs ï¼»5.0 ± 5.8ï¼½%, P < 0.05), which were both remarkably increased after YSG intervention (ï¼»38.4 ± 0.5ï¼½ ×107/ml/g and ï¼»71.5 ± 0.5ï¼½%) (P < 0.05). The OAZ model mice also exhibited degenerated and atrophic seminiferous tubules, thinner seminiferous epithelia, disorderly arranged cells at different levels, reduced number of sperm in the lumen and unclear layers of germ cells in the epididymis, while those after YSG intervention manifested regularly organized seminiferous tubules with orderly arrangement and clear layers. The expressions of the Vasa, Dazl and Snd1 genes were significantly decreased (P < 0.05), but not those of Gfra, Plzf, Stra8, Spo11, Sycp3, Sox9 and Vim (P > 0.05) in the OAZ model and YSG intervention groups as compared with those in the normal control group. The superoxide dismutase (SOD) activity in the serum was markedly reduced in the OAZ model mice as compared with that in the normal controls (P < 0.05) and increased again after YSP intervention (P < 0.05), but the opposite was the case with the expression of the superoxide anion. CONCLUSIONS: YSG can significantly reduce MMS-induced OAZ in mice, which may be associated with oxidative stress.
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Astenozoospermia/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Epididimo/efeitos dos fármacos , Testículo/efeitos dos fármacos , Animais , Astenozoospermia/induzido quimicamente , Masculino , Metanossulfonato de Metila , Camundongos , Estresse Oxidativo , Distribuição Aleatória , Contagem de Espermatozoides , Motilidade dos Espermatozoides , EspermatozoidesRESUMO
To explore the role of the testicular leptin and JAK-STAT[leptin (LEP)-JAK-STAT] pathway in testosterone biosynthesis during juvenile stages and exercise for weight loss, male C57BL/6J mice were randomly divided into normal-diet and high-fat diet groups. After 10 wk, mice in the high-fat diet-fed group were further divided randomly into obese control, obese moderate-volume exercise, and obese high-volume exercise groups. Mice in the obese moderate-volume exercise group were provided with 2 h/day, 6 days/wk swimming exercise for 8 wk, and mice in the obese high-volume exercise group underwent twice the amount of daily exercise intervention as the obese moderate-volume exercise group. The results showed that a high-fat diet causes obesity, leptin resistance, inhibition of the testicular LEP-JAK-STAT pathway, decreased mRNA and protein expression of steroidogenic factor-1, steroidogenic acute regulatory protein, and the P-450 side-chain cleavage enzyme, a decrease in the serum testosterone-to-estradiol ratio, and declines in sperm quality parameters. Both moderate and high-volume exercise were able to reduce body fat and increase the mRNA and protein expression of LEP-JAK-STAT, but only moderate exercise significantly increased the mRNA and protein expression of steroidogenic factor-1, steroidogenic acute regulatory protein, and P-450 side-chain cleavage enzyme and significantly reversed the serum testosterone-to-estradiol ratio and sperm quality parameters. These findings suggest that by impairing the testicular LEP-JAK-STAT pathway, early-stage obesity inhibits the biosynthesis of testosterone and sexual development and reduces male reproductive potential. Long-term moderate and high-volume exercise can effectively reduce body fat and improve obesity-induced abnormalities in testicular leptin signal transduction, whereas only moderate-volume exercise can reverse the negative impacts of obesity on male reproductive function.
Assuntos
Terapia por Exercício/métodos , Leptina/metabolismo , Obesidade/fisiopatologia , Obesidade/terapia , Testículo/metabolismo , Testosterona/biossíntese , Animais , Peso Corporal , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Condicionamento Físico Animal/métodos , Esforço Físico , Transdução de Sinais , Resultado do TratamentoRESUMO
BACKGROUND/AIMS: Patients with esophageal atresia (EA) and tracheoesophageal fistula (TEF) often suffer chronic respiratory tract disease. We previously reported that primary lung maldevelopment caused by deficient branching of embryonal airways in experimental EA-TEF was induced by Adriamycin. In this study, we investigated the Vascular endothelial growth factor (VEGF) pathway in the developing lung in an EA-TEF rat model. We further analyzed the effect of recombinant VEGF treatment in vitro on branching morphogenesis of embryo lungs in experimental EA-TEF. METHODS: Pregnant rats received either Adriamycin or vehicle on E7, E8 and E9. Lungs were recovered at E15, E18 and E21. Expression of VEGF and receptors (Flk-1 and Flt-1) were assessed by quantitative PCR, immunohistochemistry and immunoblotting. E13 lungs were cultured for 72 hours with 50 ng/mL of recombinant rat VEGF in serum-free medium. The rates of increase in bud count and airway contour were evaluated. RESULTS: Our results showed a significant downregulation of VEGF during pseudoglandular and canalicular stages. In contrast, there were significantly higher levels of the Flt-1 receptor in the canalicular stage, which may represent a compensatory response to decreased VEGF. However, both variables returned to normal levels at the saccular stage. Exogenous VEGF treatment enhanced hypoplastic lung growth, evidenced by the increase in bud count and airway contour. CONCLUSIONS: A VEGF signaling defect possibly plays an important role in defective embryonic airway branching. Additionally, VEGF treatment may accelerate lung growth in EA-TEF lungs.
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Atresia Esofágica/genética , Pulmão/metabolismo , Morfogênese/genética , Transdução de Sinais/genética , Fator A de Crescimento do Endotélio Vascular/genética , Animais , Western Blotting , Doxorrubicina , Atresia Esofágica/induzido quimicamente , Atresia Esofágica/embriologia , Feminino , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Humanos , Imuno-Histoquímica , Pulmão/embriologia , Pulmão/patologia , Morfogênese/efeitos dos fármacos , Técnicas de Cultura de Órgãos , Gravidez , Ratos Wistar , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/farmacologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Tempo , Fístula Traqueoesofágica/induzido quimicamente , Fístula Traqueoesofágica/embriologia , Fístula Traqueoesofágica/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/farmacologia , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/genética , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismoAssuntos
Estenose das Carótidas/terapia , Endarterectomia das Carótidas , Procedimentos Endovasculares/instrumentação , Stents , Idoso , Idoso de 80 Anos ou mais , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/mortalidade , Estenose das Carótidas/fisiopatologia , Endarterectomia das Carótidas/efeitos adversos , Endarterectomia das Carótidas/mortalidade , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/mortalidade , Feminino , Humanos , Ataque Isquêmico Transitório/mortalidade , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/mortalidade , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/mortalidade , Fatores de Tempo , Resultado do TratamentoRESUMO
Distant metastasis is the major cause of death in patients with breast cancer. Epithelial-mesenchymal transition (EMT) contributes to breast cancer metastasis. Regulator of G protein-signaling (RGS) proteins modulates metastasis in various cancers. This study identified a novel role for RGS10 in EMT and metastasis in breast cancer. RGS10 protein levels were significantly lower in breast cancer tissues compared to normal breast tissues, and deficiency in RGS10 protein predicted a worse prognosis in patients with breast cancer. RGS10 protein levels were lower in the highly aggressive cell line MDA-MB-231 than in the poorly aggressive, less invasive cell lines MCF7 and SKBR3. Silencing RGS10 in SKBR3 cells enhanced EMT and caused SKBR3 cell migration and invasion. The ability of RGS10 to suppress EMT and metastasis in breast cancer was dependent on lipocalin-2 and MIR539-5p. These findings identify RGS10 as a tumor suppressor, prognostic biomarker, and potential therapeutic target for breast cancer.
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Neoplasias da Mama , Movimento Celular , Transição Epitelial-Mesenquimal , Metástase Neoplásica , Proteínas RGS , Proteínas RGS/metabolismo , Proteínas RGS/genética , Proteínas RGS/deficiência , Humanos , Transição Epitelial-Mesenquimal/genética , Neoplasias da Mama/patologia , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Feminino , PrognósticoRESUMO
OBJECTIVES: To observe the effect of electroacupuncture (EA) preconditioning at "Quchi" (LI11) and "Xuehai" (SP10) in prevention of urticaria. METHODS: Twenty-four male SD rats were randomly divided into control, model and preconditioning of EA (Pre-EA) groups (8 rats/group). The urticaria model was established by intradermal injection of dilute allogeneic antioalbumin serum at the spots of the bilateral symmetry of the spine on the back, and followed by tail venous injection of mixture solution of egg albumin diluent, plus 0.5% Evans blue and normal saline. Ten days before the end of modeling, rats of the pre-EA group received EA stimulation of LI11 and SP10 for 20 min, once a day for 10 consecutive days. The times of rat's scratching the sensitized skin were recorded. HE staining method was used to observe the pathological changes of skin tissue, and toluidine blue staining method was used to observe the morphology of mast cells (MCs) in the skin, blood, mesentery, and peritoneal fluid, and calculate the degranulation rate. Immunohistochemical stainning was used to detect immunoglobulin E (IgE), histamine (HIS), and 5-hydroxytryptamine (5-HT) expressions in subcutaneous tissue. NOD like receptor thermal domain associated protein 3 (NLRP3) inflammasome, apoptosis related granule protein (ASC), and cysteine aspartate aminotransferase 1 (Caspase-1) protein expression levels in skin tissue were detected by Western blot. The contents of serum interleukin(IL)-1ß and IL-18 were detected using ELISA method. RESULTS: Compared with the control group, the scratching times, amount of Evans blue exudation of the sensitized blue spots, degranulation rate of MCs in skin, blood, mesentery and peritoneal fluid, the expression levels of IgE, HIS, 5-HT in subcutaneous tissue, protein expression levels of NLRP3, ASC, Caspase-1 in skin tissue, and the contents of serum IL-1ß and IL-18 were significantly increased (P<0.01, P<0.05) in the model group. In comparison with the model group, the scratching times, amount of Evans blue exudation of the sensitized blue spots, degranulation rate of MCs, the expression levels of IgE, HIS, 5-HT in subcutaneous tissue, protein expression levels of NLRP3, ASC, Caspase-1 in skin tissue, and the contents of serum IL-1ß and IL-18 in EA group were significantly decreased (P<0.01, P<0.05). CONCLUSIONS: EA preconditioning at LI11 and SP10 can prevent and treat UR by inhibiting inflammatory response, which is related to the regulation of pyroptosis.
Assuntos
Pontos de Acupuntura , Eletroacupuntura , Interleucina-1beta , Proteína 3 que Contém Domínio de Pirina da Família NLR , Ratos Sprague-Dawley , Urticária , Animais , Masculino , Ratos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Humanos , Interleucina-1beta/metabolismo , Interleucina-1beta/genética , Urticária/terapia , Urticária/metabolismo , Imunoglobulina E/sangue , Mastócitos/metabolismo , Interleucina-18/genética , Interleucina-18/metabolismo , Caspase 1/metabolismo , Caspase 1/genética , Histamina/metabolismo , Inflamação/terapia , Inflamação/prevenção & controle , Inflamação/metabolismo , Inflamação/genéticaRESUMO
The dysregulation of alternative splicing (AS) is frequently found in cancer and considered as key markers for cancer progression and therapy. Transformer 2 (TRA2), a nuclear RNA binding protein, consists of transformer 2 alpha homolog (TRA2A) and transformer 2 beta homolog (TRA2B), and plays a role in the regulation of pre-mRNA splicing. Growing evidence has been provided that TRA2A and TRA2B are dysregulated in several types of tumors, and participate in the regulation of proliferation, migration, invasion, and chemotherapy resistance in cancer cells through alteration of AS of cancer-related genes. In this review, we highlight the role of TRA2 in tumorigenesis and metastasis, and discuss potential molecular mechanisms how TRA2 influences tumorigenesis and metastasis via controlling AS of pre-mRNA. We propose that TRA2Ais a novel biomarker and therapeutic target for cancer progression and therapy.
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OBJECTIVE: To observe the effect of electroacupuncture (EA) preconditioning of "Quchi" (LI11) and "Xuehai" (SP10) on mast cell (MC) degranulation, and expressions of inositol triphosphate(IP3), reactive oxygen species (ROS), transient receptor potential (TRP) M2, calmodulin (CaM) in rats with urticaria, so as to reveal its molecular mechanism under-lying improving urticaria. METHODS: Thirty-two male SD rats were randomly divided into blank control, model, preconditioning of EA (Pre-EA) and medication groups (n=8 rats/group). The urticaria model was established by intradermal injection of dilute allogeneic antioalbumin serum at the spots of the bilateral symmetry of the spine on the back, and followed by tail venous injection of mixture solution of egg albumin diluent, plus 0.5% Evans blue and normal saline. Ten days before the end of modeling, rats of the pre-EA group received EA stimulation of LI11 and SP10 for 20 min, once a day for 10 consecutive days, and those of the medication group received gavage of loratadine tablets diluted solution (1 mg/kg) once a day for 10 days. The times of rat's scratching the sensitized skin were recorded, the diameter of the sensitized blue spots was measured and the degranulation rate of skin MCs was counted under microscope after toluidine blue staining. The expression levels of IP3, ROS, TRPM2 and CaM in the skin tissue were measured by immunohistochemistry and western blot, respectively. RESULTS: Compared with the blank control group, the scratching times, diameter of the sensitized blue spots, degranulation rate of MCs, and the expression levels of ion channel related proteins (IP3, ROS, TRPM2 and CaM) were significantly increased (P<0.01) in the model group. In comparison with the model group, the scratching times, diameter of sensitized blue spot, degranulation rate of MCs, and the expression levels of IP3, ROS, TRPM2 and CaM in both pre-EA and medication groups were significantly down-regulated (P<0.01, P<0.05). No significant differences were found between Pre-EA and medication groups in down-regulating the levels of the above-mentioned 7 indexes. CONCLUSION: EA-LI11 and SP10 preconditioning can reduce the cutaneous anaphylaxis in urticaria rats, which may be related to its effects in inhibiting the degranulation of MCs, and the expression of TRP channel related proteins.
Assuntos
Anafilaxia , Eletroacupuntura , Canais de Cátion TRPM , Urticária , Ratos , Masculino , Animais , Mastócitos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio , Canais de Cátion TRPM/genética , Degranulação Celular , Transdução de SinaisRESUMO
OBJECTIVE: To observe the effect of electroacupuncture (EA) pretreatment at "Quchi "(LI11) and "Xuehai "(SP10) on expression of interleukin (IL)-33, suppression of tumorigenicity 2 (ST2) and mast cell degranulation in sensitive area of skin tissue in rats with urticaria, so as to explore its mechanisms underlying prevention of urticaria. METHODS: A total of 32 male SD rats were randomly divided into blank control, model, EA preconditioning and medication groups, with 8 rats in each group. The urticaria model was established by topical injection of the prepared anti-ovalbumin serum (foreign serum, 0.1 mL/spot) along the bilateral sides of the spinal column on the back, followed by injection of mixture solution of ovalbumin, 0.5% evans blue and normal saline via the tail vein 48 h later. EA intervention (2 Hz/15 Hz, 1 mA) was applied to bilateral LI11 and SP10 for 20 min, once daily for 7 d before modeling.Back sensitization was started from the 5th day on. Rats of the medication group received gavage of loratadine, and those of the model group received gavage of the same volume of normal saline. The diameter of evans blue spots at the back skin tissue was measured; the histopathological changes of the blue spot tissues were observed by light microscope after H.E. staining. The state of degranulation of mast cells in the subcutaneous loose connective tissue was observed by using toluidine blue staining. Serum IgE and histamine contents were detected by ELISA, and the immunoactivity of IL-33 and ST2 in the skin and subcutaneous tissues of the sensitized spots (evans blue exudation spots) was observed by immunohistochemistry. RESULTS: Compared with the blank control group, the diameter of evans blue spot, degranulation rate of mast cells, serum IgE and histamine contents, and the immunoactivity of IL-33 and ST2 in the evans blue exudation spot tissues were significantly increased in the model group (P<0.01). In comparison with the model group, the increase of the above-mentioned indexes was reversed in both EA and medication groups (P<0.01ï¼P<0.05). No significant differences were found between the EA and medication groups in down-regulating the levels of the 6 indexes. H.E. staining of the blue spot tissues of rats in the model group showed incomplete structure of the epidermal layer of the skin, unclear interface of tissues, incomplete keratinization, chaotic epidermal cells, disorderly arrangement of fibers in the dermis, and infiltration of inflammatory cells and edema, which was relatively milder in the EA and medication groups. CONCLUSION: EA preconditioning can prevent urticaria (reduce size and sensitive reactions) in rats, which may be associated with its functions in lowering the level of IgE through inhibiting IL-33 and ST2.
Assuntos
Terapia por Acupuntura , Eletroacupuntura , Urticária , Ratos , Masculino , Animais , Ratos Sprague-Dawley , Mastócitos , Proteína 1 Semelhante a Receptor de Interleucina-1 , Histamina , Azul Evans , Interleucina-33/genética , Solução Salina , Urticária/genética , Urticária/terapia , Imunoglobulina E , Pontos de Acupuntura , Receptores de Interleucina-1RESUMO
BACKGROUND: Heterologous boosting is suggested to be of use in populations who have received inactivated COVID-19 vaccines. We aimed to assess the safety and immunogenicity of a heterologous vaccination with the mRNA vaccine CS-2034 versus the inactivated BBIBP-CorV as a fourth dose, as well as the efficacy against the SARS-CoV-2 omicron (BA.5) variant. METHODS: This trial contains a randomised, double-blind, parallel-controlled study in healthy participants aged 18 years or older (group A) and an open-label cohort in participants 60 years and older (group B), who had received three doses of inactivated whole-virion vaccines at least 6 months before enrolment. Pregnant women and people with major chronic illnesses or a history of allergies were excluded. Eligible participants in group A were stratified by age (18-59 years and ≥60 years) and then randomised by SAS 9.4 in a ratio of 3:1 to receive a dose of the mRNA vaccine (CS-2034, CanSino, Shanghai, China) or inactivated vaccine (BBIBP-CorV, Sinopharm, Beijing, China). Safety and immunogenicity against omicron variants of the fourth dose were evaluated in group A. Participants 60 years and older were involved in group B for safety observations. The primary outcome was geometric mean titres (GMTs) of the neutralising antibodies against omicron and seroconversion rates against BA.5 variant 28 days after the boosting, and incidence of adverse reactions within 28 days. The intention-to-treat group was involved in the safety analysis, while all patients in group A who had blood samples taken before and after the booster were involved in the immunogenicity analysis. This trial was registered at the Chinese Clinical Trial Registry Centre (ChiCTR2200064575). FINDINGS: Between Oct 13, and Nov 22, 2022, 320 participants were enrolled in group A (240 in the CS-2034 group and 80 in the BBIBP-CorV group) and 113 in group B. Adverse reactions after vaccination were more frequent in CS-2034 recipients (158 [44·8%]) than BBIBP-CorV recipients (17 [21·3%], p<0·0001). However, most adverse reactions were mild or moderate, with grade 3 adverse reactions only reported by eight (2%) of 353 participants receiving CS-2034. Heterologous boosting with CS-2034 elicited 14·4-fold (GMT 229·3, 95% CI 202·7-259·4 vs 15·9, 13·1-19·4) higher concentration of neutralising antibodies to SARS-CoV-2 omicron variant BA.5 than did homologous boosting with BBIBP-CorV. The seroconversion rates of SARS-CoV-2-specific neutralising antibody responses were much higher in the mRNA heterologous booster regimen compared with BBIBP-CorV homologous booster regimen (original strain 47 [100%] of 47 vs three [18·8%] of 16; BA.1 45 [95·8%] of 48 vs two [12·5%] 16; and BA.5 233 [98·3%] of 240 vs 15 [18·8%] of 80 by day 28). INTERPRETATION: Both the administration of mRNA vaccine CS-2034 and inactivated vaccine BBIBP-CorV as a fourth dose were well tolerated. Heterologous boosting with mRNA vaccine CS-2034 induced higher immune responses and protection against symptomatic SARS-CoV-2 omicron infections compared with homologous boosting, which could support the emergency use authorisation of CS-2034 in adults. FUNDING: Science and Technology Commission of Shanghai, National Natural Science Foundation of China, Jiangsu Provincial Science Fund for Distinguished Young Scholars, and Jiangsu Provincial Key Project of Science and Technology Plan. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.
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COVID-19 , Complicações Infecciosas na Gravidez , Gravidez , Humanos , Adulto , Feminino , Adolescente , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , China , SARS-CoV-2 , Anticorpos Neutralizantes , Método Duplo-Cego , Imunogenicidade da Vacina , Anticorpos AntiviraisRESUMO
BACKGROUND: Cardiac shock wave therapy (CSWT) improves cardiac function in patients with severe coronary artery disease (CAD). We aimed to evaluate the clinical outcomes of a new CSWT treatment regimen. METHODS: The 55 patients with severe CAD were randomly divided into 3 treatment groups. The control group (n = 14) received only medical therapy. In group A ( n = 20), CSWT was performed 3 times within 3 months. In group B ( n = 21), patients underwent 3 CSWT sessions/week, and 9 treatment sessions were completed within 1 month. Primary outcome measurement was 6-minute walk test (6MWT). Other measurements were also evaluated. RESULTS: The 6MWT, CCS grading of angina, dosage of nitroglycerin, NYHA classification, and SAQ scores were improved in group A and B compared to control group. CONCLUSIONS: A CSWT protocol with 1 month treatment duration showed similar therapeutic efficacy compared to a protocol of 3 months duration. CLINICAL TRIAL REGISTRY: We have registered on ClinicalTrials.gov, the protocol ID is CSWT IN CHINA.
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Doença da Artéria Coronariana/terapia , Ondas de Choque de Alta Energia/uso terapêutico , Idoso , Angina Pectoris/etiologia , Angina Pectoris/prevenção & controle , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/fisiopatologia , Tolerância ao Exercício , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do TratamentoRESUMO
For the unexpected situations occur that 1,3-dinitrobenzene volatile gas leaks in industrial production process, designed the differential characteristics absorption detection system for 1,3-dinitrobenzene volatile gas based on THz spectrum technique. The method can detect the concentration of trace 1,3-dinitrobenzene toxic gases through the THz characteristic wavelengths differential absorption method. System dealt with THz characteristics wavelengths of the two chambers, which provide difference dates, a group is standard air, and the other group tested the sample gas. Four main absorption bands of 1,3-dinitrobenzene is at 0.635, 0.912, 1.095 and 1.435 THz nearby in detection results, and according to the ratio of absorption coefficient in the corresponding absorption band it calculated the accurate amplitude from the corresponding wavelengths, at last the gas concentration was inversed. After the two traditional methods (chromatography and infrared absorption method) of experimental analysis and THz absorption detection method of the simulation study shows, precision of the detection capabilities of chromatography is high and error is small. But the chromatography separation time varies with the material, long cycle, slow; chromatography can not achieve real-time detection speed to realize real-time detection. Infrared absorption of environmental humidity is high, subject to drying. At the same time, THz absorption of environmental humidity is low; THz absorption method also has important characteristics of real time, strong anti-jamming, especially the water vapor, so it is more suitable for practical application.
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OBJECTIVE: To evaluate the efficacy and safety of linezolid in the treatment of post-neurosurgical intracranial methicillin-resistant Staphylococcus (MRS) infection. METHODS: The data from 14 patients, admitted to neurological intensive care unit (ICU) of Medical College of Chinese People's Armed Police Forces between March 2009 and November 2011, were retrospectively analyzed. All these cases suffered from post-neurosurgical intracranial infection by MRS and received linezolid treatment. Blood and cerebrospinal fluid (CSF) were collected before and 7 days and 14 days after treatment for routine and bacteriological examinations to assess clinical efficacy and adverse reactions of linezolid. RESULTS: After 14-day treatment with linezolid, the clinical and laboratory parameters showed significant improvement: glucose (mmol/L) in CSF rose from 1.00 (0.65) to 3.15 (1.60), protein (mg/L) in CSF dropped from 2238.50 (2072.50) to 606.50 (217.30), white blood cell count [×106/L] in CSF fell from 920.00 (1587.50) to 30.00 (40.00), and the number of patients with CSF neutrophil ratio>0.20 was reduced from 14 to 1 (all P < 0.01). In addition, serum procalcitonin level (µg/L) was significantly reduced from 0.65 (1.16) to 0.08 (0.09) after linezolid therapy (P < 0.01). Total effective rate was 85.7% (12/14), and CSF bacterial clearance rate reached 100%. No adverse events were found during the treatment. CONCLUSION: Linezolid could effectively control post--neurosurgical intracranial MRS infection and alleviate the inflammatory responses with safety.
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Acetamidas/uso terapêutico , Antibacterianos/uso terapêutico , Infecções do Sistema Nervoso Central/tratamento farmacológico , Oxazolidinonas/uso terapêutico , Infecções Estafilocócicas/tratamento farmacológico , Adolescente , Adulto , Idoso , Feminino , Humanos , Linezolida , Masculino , Resistência a Meticilina , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos/efeitos adversos , Período Pós-Operatório , Estudos Retrospectivos , Adulto JovemRESUMO
Data mining is an analytical method for revealing the implicit internal relations among the data elements, and is also widely used in the field of acupuncture and moxibustion of traditional Chinese medicine. However, there exist some significant deficits in the rationality of design and implementation, preciseness, repeatability, comprehensiveness, objectivity and depth of insights in some current acupuncture data mining researches. In the present paper, we summarized the literature on acupuncture data mining published in the past five years, and analyzed their common shortcomings in the design, implementation and reporting process, including too broad research scope, fuzzy and limited descriptions about the inclusion criteria, not definite retrieval scope and strategy, rarely seen original researches about the assessment of the report quality, lack of detailed descriptions about the literature screening and data processing procedure, incomplete narration about the research outcomes and their clinical significance, and lack of comprehensiveness and subjectiveness and available coping strategies in the discussion of the research papers, etc., in order to promote the improvement of literature methodology and quality of acupuncture data mining research, and then improve the reliability and clinical reference value of such research results.
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Terapia por Acupuntura , Moxibustão , Reprodutibilidade dos Testes , Mineração de Dados , Medicina Tradicional ChinesaRESUMO
Objective: The aim of this research was to study the expression of Piezo1 in a rat temporomandibular joint osteoarthritis animal model and to explore its mechanism for inducing inflammatory changes. Methods: A total of 24male SD rats aged approximately 8 weeks were randomly divided into three groups: the blank control group, complete Freund's adjuvant group (CFA), and CFA + inhibitor (GsMTx4) group. After 3 weeks, the condylar heads of the rats were evaluated by micro-CT, HE, immunohistochemistry, safranin O staining, and other experimental techniques. Protein was extracted from the subchondral bone, and the changes in Piezo1, Smad3, and pSmad3 levels in each group were detected by Western blotting. p < 0.05 was considered to indicate statistical significance. Results: The degree of damage to the cartilage and subchondral bone in the Piezo1 inhibitor group was smaller than that in the CFA group. The expression level of Piezo1 in the CFA group was higher than that in the other groups, and the difference was statistically significant. The expression of pSmad3 in the CFA group was also higher than that in the other groups (p < 0.05). Conclusion: Piezo1 is expressed in the condylar cartilage and subchondral bone of rats, and the degree of condylar destruction can be improved by influencing the pSmad3 expression.
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BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is the most common respiratory disease in clinic. Traditional Chinese medicine (TCM) lung rehabilitation has gradually been valued in the field of prevention and treatment of COPD. Acupuncture, as an important part of TCM lung rehabilitation, is carried out in clinical extensively and application. It has the advantage of improving the symptoms and quality of life of COPD cases, but the evidence-based proof is limited. METHODS: Eight databases will be systematically retrieved from their inceptions to December 2021. This study will include randomized controlled trials of acupuncture in the treatment of COPD with stable stage. The main outcome will include clinical effective rate, TCM symptom score, quality of life, dyspnea, exercise capacity, lung function, frequency of acute exacerbation, adverse events. Literature screening, quality evaluation and information extraction will be completed by two independent researchers. Revman 5.3 software will be used to perform meta-analysis. Assessment of multiple systematic reviews-2 tool will be used for evaluating the methodological quality of systematic review (SR), grading of recommendations assessment will for rating the quality of evidence, and consolidated standards of reporting trials and Standards for Reporting Interventions in Clinical Trials of Acupuncture tool will for assessing the reporting quality of randomized controlled trials. RESULTS: The findings of this SR will be presented at relevant conferences and submitted for peer-review publication. CONCLUSIONS: The findings of this SR will provide up-to-date summary proof for evaluating the effectiveness and safety of acupuncture for COPD.
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Terapia por Acupuntura , Doença Pulmonar Obstrutiva Crônica , Humanos , Metanálise como Assunto , Doença Pulmonar Obstrutiva Crônica/terapia , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Revisões Sistemáticas como Assunto , Resultado do TratamentoRESUMO
This article explores the obesity state and the changes in the level of lipophagy in adipose tissue after exercise to lose weight, so as to provide direction and basis for theoretical research on obesity prevention and control. We established a high-fat diet model of obese mice, and applied exercise intervention and intraperitoneal injection of chloroquine to inhibit autophagy. Long-term high-fat diet can cause obesity in mice, and the process of lipophagy is inhibited, which may be one of the reasons for fat accumulation. Eight weeks of aerobic exercise can effectively reduce the weight of obese mice and promote lipolysis; this process is mainly completed by lipase decomposition, in addition to require the participation of the lipophagy process.
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Tecido Adiposo , Lipólise , Animais , Autofagia , Dieta Hiperlipídica , Masculino , Camundongos , Camundongos Obesos , ObesidadeRESUMO
OBJECTIVE: To explore the interventional mechanism of electroacupuncture (EA) of "Zusanli"(ST36)based on the involvement of mast cells/ transient receptor potential vanilloid type1 (TRPV1) signaling pathway in relieving visceral hypersensitivity in functional dyspepsia (FD) rats. METHODS: Sixty SD rats (half male and half female, 10 days in age) were randomly divided into normal control, model, medication (ketotifen) and EA groups, with 15 rats in each group. The FD model was established by gavage of iodoacetamide combined with tail clamping (stress stimulation). Rats of the medication group received intraperitoneal injection of ketotifen (1 mg·kg-1·d-1) for 14 d, and those of the EA group received EA of ST36 for 20 min, once a day for 14 d. An air-balloon was inserted into the rat's stomach for recording changes of the intragastric pressure (mL/mm Hg) via a pressure transducer. The visceral hypersensitivity was assessed using abdominal withdrawal reflex (AWR) score and the number and degranulation of mast cells of gastric mucosa were observed using toluidine blue staining. The expression levels of TRPV1 and proteinase activated receptor 2 (PAR2) in the stomach were observed using immunofluorescence histochemistry and Western blot, separately, and the contents of SP and CGRP in the stomach detected using ELISA. RESULTS: When the intragastric pressure was at 50, 60 and 70 mm Hg, the gastric compliance was significantly decreased (P<0.01), and the levels of visceral sensitivity increased in the model group ï¼P<0.01ï¼ã TRPV1 immunofluorescence tensity, expression of PAR2 and TRPV1 proteins, and contents of SP and CGRP in the stomach were considerably up-regulated in the model group compared with the normal control group (P<0.01). In comparison with the model group, under intragastric pressure of 50ï¼60 and 70 mm Hg, the gastric compliance was obviously increased, and the visceral hypersensitivity decreased in the EA group ï¼P<0.01,P<0.05ï¼. TRPV1 immunofluorescence intensity, expression levels of PAR2 and TRPV1 proteins, and the contents of SP and CGRP in the stomach were considerably down-regulated in both medication and EA groups compared with the model group (P<0.01, P<0.05). The therapeutic effect of EA was significantly superior to that of medication in up-regulating the gastric compliance ï¼at 70 mm Hgï¼, and down-regulating the contents of SP and CGRP (P<0.05). No significant differences were found between the EA and medication groups in up-regulating gastric compliance at intragastric pressure of 50 and 60 mm Hg, and in down-regulating the visceral sensitivity, TRPV1 fluorescence intensity, and expression of PAR2 and TRPV1 proteins (P>0.05). Toluidine blue staining showed an apparent increase of mast cell number with obvious degranulation in the gastric mucosa of rats in the model group, which was milder in the EA and medication groups. CONCLUSION: EA of ST36 can suppress visceral hypersensitivity and increase the gastric compliance in FD rats, which may be related with its effects in inhibiting the activation of gastric mast cells, and down-regulating the expression of gastric PAR2 and TRPV1 proteins and SP and CGRP contents.