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Real-life data on guselkumab in psoriasis are limited and not available in China hitherto. This study aimed to evaluate the short-term effectiveness and safety of guselkumab in patients with psoriasis under Chinese real-life conditions and to explore the effect of guselkumab on CD4+ CD25+ Foxp3+ regulatory T cells (Tregs). A Chinese prospective and real-life study involving patients with psoriasis in Dermatology Hospital of Southern Medical University, Guangzhou, China from April to September 2020 was conducted. A total of 45 patients with psoriasis were finally enrolled in the study. Psoriasis Area Severity Index (PASI) 90 and 100 responses at week 16 were achieved by 88.6% and 45.5% of patients, respectively. The analysis of PASI response in different subgroups showed no statistically significant difference. Univariate logistic regression analysis revealed that at week 16, none of the variables were associated with decreasing PASI 90 response, whereas age at onset of disease was a predictor of PASI 100 response. Dynamic detection of CD4+ CD25+ Foxp3+ Tregs frequency from peripheral blood suggested a stable maintained trend in terms of guselkumab treatment duration. No severe adverse events occurred during the follow-up period. This study confirmed the short-term effectiveness and safety of guselkumab, as well as its good tolerance against psoriasis, in the Chinese population. Guselkumab treatment maintains levels of Tregs in patients with psoriasis.
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Anticorpos Monoclonais , Psoríase , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , China , Humanos , Estudos Prospectivos , Psoríase/diagnóstico , Psoríase/tratamento farmacológico , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
Piebaldism is a rare, autosomal dominant and congenital pigmentary disorder characterized by stable depigmentation of the skin and white forelock. Mutations in KIT or SNAI2 genes result in piebaldism. Most individuals with piebaldism have a family history of the disorder. Herein, we report a 5-month-old Chinese girl with severe piebaldism but no family history thereof. She has white forelock and large patches of depigmentation in the jaw, central anterior trunk, perineum and extremities. We performed whole-exome and Sanger sequencing and identified a de novo KIT mutation (NM_000222.2: c.2657G>A, p.Gly886Val) in exon 18 of KIT in the proband. Currently, this mutation is located in the most extreme C-terminal of the tyrosine kinase domain 2 of the KIT gene amongst all reported mutations and causes a severe clinical phenotype. We further reviewed literature on piebaldism and summarized 79 KIT gene mutations that lead to this disease. Our study may expand knowledge on the genotype-phenotype correlation in piebaldism and serve as a reference for genetic counseling and prenatal diagnosis of affected families.
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Predisposição Genética para Doença , Piebaldismo/genética , Transtornos da Pigmentação/genética , Proteínas Proto-Oncogênicas c-kit/genética , Pré-Escolar , Feminino , Humanos , Mutação/genética , Linhagem , Piebaldismo/patologia , Transtornos da Pigmentação/patologia , Sequenciamento do ExomaRESUMO
BACKGROUND: Acrodermatitis enteropathica (AE) is a rare autosomal recessive hereditary skin disease caused by mutations in the SLC39A4 gene and is characterized by periorificial dermatitis, alopecia and diarrhoea due to insufficient zinc absorption. Only one of the three known sets of twins with AE has genetic information. This case reports the discovery of new mutation sites in rare twin patients and draws some interesting conclusions by analysing the relationship between genetic information and clinical manifestations. CASE PRESENTATION: Here, we report a pair of 16-month-old twin boys with AE exhibiting periorificial and acral erythema, scales and blisters, while subsequent laboratory examination showed normal plasma zinc and alkaline phosphatase levels. Further Sanger sequencing demonstrated that the patients were compound heterozygous for two unreported SLC39A4 mutations: a missense mutation in exon 5 (c.926G > T), which led to a substitution of the 309th amino acid residue cysteine with phenylalanine, a splice site mutation occurring in the consensus donor site of intron 5 (c.976 + 2 T > A). A family study revealed that the boys' parents were heterozygous carriers of these two mutations. CONCLUSION: We identified a new compound heterozygous mutation in Chinese twins with AE, which consisted of two previous unreported variants in exon 5 and intron 5 of SLC39A4. We propose an up-to-date review that different mutations in SLC39A4 may exhibit different AE manifestations. In conjunction with future research, our work may shed light on genotype-phenotype correlations in AE patients and provide knowledge for genetic counselling and treatment for AE patients.
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Acrodermatite/genética , Proteínas de Transporte de Cátions/genética , Doenças em Gêmeos/genética , Mutação , Zinco/deficiência , Acrodermatite/tratamento farmacológico , Feminino , Heterozigoto , Humanos , Lactente , Masculino , Linhagem , Zinco/uso terapêuticoRESUMO
Curcumin, a dietary supplement or herbal medicine from Curcuma longa, has shown antitumor activity in different cancer cell lines and clinical trials. CA916798, a novel protein, is overexpressed in multidrug-resistant tumor cells. This study aimed to assess the effects of curcumin on regulating chemosensitivity in cisplatin-resistant non-small cell lung cancer (NSCLC) cells in vitro and to explore the underlying molecular mechanisms. Human cisplatin-sensitive A549 and cisplatin-resistant A549/CDDP lung adenocarcinoma cells were treated with curcumin to assess cell viability and gene modulations using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting. CA916798 shRNA and point mutations were used to assess the CA916798 functions and phosphorylation sites. Bisdemethoxycurcumin sensitized cisplatin-resistant lung cancer cells to various chemotherapeutic agents, including cisplatin. Bisdemethoxycurcumin reduced the levels of CA916798 mRNA and protein in A549 and A549/CDDP cells, while it also suppressed phosphatidylinositol-3-kinase (PI3K)/AKT signaling. CA916798, as a downstream gene, interacted with AKT after bisdemethoxycurcumin treatment in A549 and A549/CDDP cells. Moreover, A549/CDDP cells expressing the point-mutated CA916798-S20D protein were more resistant to cisplatin and bisdemethoxycurcumin, whereas tumor cells expressing CA916798-S20A, CA916798-S31A, CA916798-S60A, CA916798-S93A, or CA916798-T97A (different sites of amino acid phosphorylation) showed similar sensitivity or resistance to cisplatin and bisdemethoxycurcumin, compared with the control cells. Bisdemethoxycurcumin is able to sensitize cisplatin-resistant NSCLC cells to chemotherapeutic agents by inhibition of CA916798 and PI3K/AKT activities. Moreover, phosphorylation of CA916798 at the S20 residue plays a critical role in mediating bisdemethoxycurcumin antitumor activity.
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Adenocarcinoma/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Curcumina/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , Proteínas de Neoplasias/metabolismo , Transdução de Sinais/efeitos dos fármacos , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Nus , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/genética , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismoRESUMO
CONTEXT: Geniposidic acid, one of the main active ingredients in Gardenia jasminoides J. Ellis (Rubiaceae), may also possess important pharmacological activities for cardiovascular disorders similar to other derivatives, such as geniposide. OBJECTIVE: To evaluate its anti-atherosclerosis (anti-AS) effect, the related pharmacological activities and possible cellular mechanisms were studied. MATERIALS AND METHODS: Thirty rabbits were randomly divided into normal control group, model control group, and geniposidic acid subgroups. In the AS model, its effects on the intima/media thickness ratio and aortic morphology were observed. In the study of primary cultured endothelial cells (ECs) and human umbilical artery smooth muscle cells (HUASMCs), its activities on both ECs and HUASMCs proliferation, HUASMCs' migration were also studied. RESULTS: Compared with the model control group, the plaque area, intima/media thickness ratio, and intimal foam cells number in geniposidic acid (80, 160, and 240 mg/kg) subgroups were significantly improved (p < 0.05). By HE staining, the activities of geniposidic acid on relieving ECs shedding and improving aortic morphology disorders were also demonstrated. From the results of CCK-8 testing, only 100 µg/ml geniposidic acid performed significant inhibition on SMC proliferation. The relative IC50 of geniposidic acid on SMC inhibition was 87.73 µg/ml. Geniposide acid also showed promotion effect on ECs proliferation, and the related ED50 of geniposidic acid was 86.05 µg/ml. Besides, only 50 and 100 µg/ml geniposidic acid showed obvious inhibition on SMC migration from the upper chamber (p < 0.05). DISCUSSION AND CONCLUSION: The effects of geniposidic acid on protecting vascular endothelium and reversing plaque formation in an atherosclerotic model were demonstrated.
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Aterosclerose/tratamento farmacológico , Medicamentos de Ervas Chinesas/isolamento & purificação , Glucosídeos Iridoides/isolamento & purificação , Miócitos de Músculo Liso/efeitos dos fármacos , Animais , Aorta Torácica/efeitos dos fármacos , Aorta Torácica/patologia , Aterosclerose/patologia , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Gardenia/química , Células Endoteliais da Veia Umbilical Humana , Humanos , Glucosídeos Iridoides/farmacologia , Glucosídeos Iridoides/uso terapêutico , Masculino , Estrutura Molecular , Miócitos de Músculo Liso/citologia , Coelhos , Túnica Íntima/efeitos dos fármacos , Túnica Íntima/patologia , Túnica Média/efeitos dos fármacos , Túnica Média/patologiaRESUMO
Myeloproliferative neoplasms (MPNs) occur due to the abnormal proliferation of one or more terminal myeloid cell lines in peripheral blood. Subjects suffering from MPNs display a high burden of cardiovascular risk factors, and thrombotic events are often the cause of death in this population of patients. Herein, we provide a brief overview of dyslipidemia and metabolic syndrome and their epidemiology in MPNs and examine the common molecular mechanisms between dyslipidemia, metabolic syndrome, and MPNs, with a special focus on cardiovascular risk, atherosclerosis, and thrombotic events. Furthermore, we investigate the impact of dyslipidemia and metabolic syndrome on the occurrence and survival of thrombosis in MPN patients, as well as the management of dyslipidemia in MPNs, and the impact of MPN treatment on serum lipid concentrations, particularly as side/adverse effects reported in the context of clinical trials.
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A high-glucose environment is involved in the progression of diabetes mellitus (DM). This study aims to explore the regulatory effects of quercetin (QUE) on autophagy and apoptosis after myocardial injury in rats with DM. The type 2 DM rat models were constructed using low-dose streptozotocin (STZ) treatment combined with a high-carbohydrate (HC) diet in vivo. Compared with the control group, the body weight was decreased, whereas blood pressure, blood glucose, and the LVW/BW ratio were increased in the diabetic group. The results showed that the myocardial fibers were disordered in the diabetic group. Moreover, we found that the myocardial collagen fibers, PAS-positive cells, and apoptosis were increased, whereas the mitochondrial structure was destroyed and autophagic vacuoles were significantly reduced in the diabetic group compared with the control group. The expression levels of autophagy-related proteins LC3 and Beclin1 were decreased, whereas the expression levels of P62, Caspae-3, and Bax/Bcl-2 were increased in the diabetic group in vitro and in vivo. Moreover, QUE treatment alleviated the cellular oxidative stress reaction under high-glucose environments. The results of immunoprecipitation (IP) showed that the autophagy protein Beclin1 was bound to Bcl-2, and the binding capacity increased in the HG group, whereas it decreased after QUE treatment, suggesting that QUE inhibited the binding capacity between Beclin1 and Bcl-2, thus leading to the preservation of Beclin1-induced autophagy. In addition, the blood pressure, blood glucose, and cardiac function of rats were improved following QUE treatment. In conclusion, QUE suppressed diabetic myocardial injury and ameliorated cardiac function by regulating myocardial autophagy and inhibition of apoptosis in diabetes through the AMPK/mTOR signaling pathway.
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Proteínas Quinases Ativadas por AMP , Apoptose , Autofagia , Diabetes Mellitus Experimental , Quercetina , Transdução de Sinais , Serina-Treonina Quinases TOR , Animais , Autofagia/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Quercetina/farmacologia , Transdução de Sinais/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Masculino , Proteínas Quinases Ativadas por AMP/metabolismo , Ratos Sprague-Dawley , Ratos , Modelos Animais de Doenças , Miocárdio/metabolismo , Miocárdio/patologia , Estreptozocina , Cardiomiopatias Diabéticas/etiologia , Cardiomiopatias Diabéticas/tratamento farmacológico , Cardiomiopatias Diabéticas/metabolismo , Cardiomiopatias Diabéticas/prevenção & controle , Fitoterapia , Proteína Beclina-1/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/complicaçõesRESUMO
The phytochemistry, cardiovascular pharmacology, toxicology, side effect, and further development prospects of Gardenia jasminoides J. Ellis (GJE) and its main constituents crocins and iridoid glycosides were studied. Numerous studies have confirmed that crocins and iridoid glycosides had effects of antioxidation, anti-inflammatory, anti-atherosclerosis, anti-ischemic brain injuries, anti-platelet aggregation, anti-hyperglycemia, anti-hyperlipidemia, anti-hypertension, and so on. Some of them might be related to several attractive pharmacodynamic actions of GJE such as promoting endothelium growth, protecting neurons, and inducing their differentiation. Both of them make it possible for GJE to prevent and cure thromboembolism and cardiovascular diseases well. From our own basic pharmacological research of GJE extract on several rat models, it has been known that GJE extract markedly prolonged bleeding time and inhibited platelet aggregation and thrombosis. It has significant proliferation effect on both endothelial cells and endothelial progenitor cells as well. As the mechanisms of GJE on those diseases were discussed and summarized, questions about its genetoxicity and hepatotoxicity were also discussed during its safety study to make the foundation for long-term medication and clinical research in the near future.
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Carotenoides , Gardenia/química , Glicosídeos Iridoides , Animais , Anti-Inflamatórios não Esteroides/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Aterosclerose/tratamento farmacológico , Cardiotônicos/uso terapêutico , Carotenoides/química , Carotenoides/isolamento & purificação , Carotenoides/farmacologia , Modelos Animais de Doenças , Frutas , Hiperlipidemias/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Glicosídeos Iridoides/química , Glicosídeos Iridoides/isolamento & purificação , Glicosídeos Iridoides/farmacologia , Inibidores da Agregação Plaquetária/uso terapêutico , RatosRESUMO
Nonsmall cell lung cancer (NSCLC) is a major subtype of lung cancer, causing substantial cancer-related deaths worldwide. However, the molecular basis of NSCLC development and progression remains understudied. Recently, a circular RNA, circDLG1, has been implicated in carcinogenesis and cancer metastasis. Yet, how circDLG1 affects NSCLC progression has not been reported. Here this study aims to elucidate the role of circDLG1 in NSCLC. First, we found that circDLG1 was significantly upregulated in both the GEO dataset and NSCLC tissues. Next, we silenced the expression of circDLG1 in NSCLC cell lines. Knockdown of circDLG1 upregulated miR-144 and downregulated Protein kinase B (AKT)/mechanistic target of rapamycin (mTOR), resulting in suppression of the proliferation activity and metastasis ability of NSCLC. In addition, circDLG1 knockdown significantly decreased the expression of the mesenchymal markers, proliferating cell nuclear antigen (PCNA), and N-cadherin, while increasing the expression level of E-cadherin. In conclusion, we demonstrate that circDLG1 promotes the pathogenesis and progression of NSCLC by regulating the miR-144/AKT/mTOR signaling axis, providing potential diagnostic and therapeutic targets for designing innovative treatment strategies.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , MicroRNAs , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , RNA Circular/genética , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Oncogenes/genética , Proliferação de Células/genética , Linhagem Celular TumoralRESUMO
Hong Kong is a well-developed city with outstanding healthcare services, leading to the highest life expectancy in the world. Paradoxically, the quality of end-of-life care in this city lagged behind that of many other high-income regions. Possibly, the advances in medicine contribute to the death denial culture, hindering communication about end-of-life care. This paper discusses challenges arisen due to poor public awareness and professional training and local initiatives to promote advance care planning in the community.
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Planejamento Antecipado de Cuidados , Medicina , Humanos , Hong Kong , AlemanhaRESUMO
Background: Sebaceous gland hyperplasia (SGH) is a benign cutaneous proliferation of the sebaceous glands that are mostly present on the face or the neck of older adults. They typically appear as single or multiple soft umbilicated papules; however, in challenging cases, it can be difficult to distinguish them from trichoepitheliomas, base cell carcinomas, or other tumors. Although pathological results have diagnostic value, the significance of non-invasive examinations in diagnosis and differential diagnosis is also worth exploring. Objectives: This study aimed to describe the dermoscopic and reflectance confocal microscopy (RCM) features of SGH. Methods: A total of 31 patients diagnosed with SGH, according to clinical and histopathological standards, were examined using dermoscopy and RCM between March 2018 and January 2022. Results: Dermoscopically, lesions revealed a yellowish-red background and a faint-yellow background in 25 (80.65%) and six cases (19.35%), respectively. White-yellowish lobulated structures in the center of the lesion were present in 31 patients (100%) and umbilications in 19 patients (61.29%). Crown vessels at the periphery of the lesions were observed in 11 patients (35.48%), whereas irregular linear vessels were observed on the surface of the lesions in 18 patients (58.06%). Under RCM, all lesions presented a honeycomb pattern in the epidermis and the typical morulae-shaped sebaceous lobules in the dermis. A dilated follicular infundibulum was observed in 15 patients (48.39%) and dilated vessels in 26 patients (83.87%). Conclusion: Dermoscopy and RCM enabled us to describe the imaging features of SGH. Combining these two useful tools provides a non-invasive basis for accurate clinical diagnosis.
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As an important treatment for acute myeloid leukemia, allogeneic hematopoietic stem cell transplantation (allo-HSCT) plays an important role in reducing relapse and improving long-term survival. With rapid advancements in basic research in molecular biology and immunology and with deepening understanding of the biological characteristics of hematopoietic stem cells, allo-HSCT has been widely applied in clinical practice. During allo-HSCT, preconditioning, the donor, and the source of stem cells can be tailored to the patient's conditions, greatly broadening the indications for HSCT, with clear survival benefits. However, the risks associated with allo-HSCT remain high, i.e. hematopoietic reconstitution failure, delayed immune reconstitution, graft-versus-host disease, and post-transplant relapse, which are bottlenecks for further improvements in allo-HSCT efficacy and have become hot topics in the field of HSCT. Other bottlenecks recognized in the current treatment of individuals diagnosed with acute myeloid leukemia and subjected to allo-HSCT include the selection of the most appropriate conditioning regimen and post-transplantation management. In this paper, we reviewed the progress of relevant research regarding these aspects.
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Classical Philadelphia-negative myeloproliferative neoplasms (MPNs), i.e., polycythemia vera, essential thrombocythemia, and primary/secondary myelofibrosis, are clonal disorders of the hematopoietic stem cell in which an uncontrolled proliferation of terminally differentiated myeloid cells occurs. MPNs are characterized by mutations in driver genes, the JAK2V617F point mutation being the most commonly detected genetic alteration in these hematological malignancies. Thus, JAK inhibition has emerged as a potential therapeutic strategy in MPNs, with ruxolitinib being the first JAK inhibitor developed, approved, and prescribed in the management of these blood cancers. However, the use of ruxolitinib has been associated with a potential risk of infection, including opportunistic infections and reactivation of hepatitis B. Here, we briefly describe the association between ruxolitinib treatment in MPNs and hepatitis B reactivation.
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The function of mitochondrial fusion and fission is one of the important factors causing ischemia-reperfusion (I/R) injury in diabetic myocardium. Aldehyde dehydrogenase 2 (ALDH2) is abundantly expressed in heart, which involved in the regulation of cellular energy metabolism and stress response. However, the mechanism of ALDH2 regulating mitochondrial fusion and fission in diabetic myocardial I/R injury has not been elucidated. In the present study, we found that the expression of ALDH2 was downregulated in rat diabetic myocardial I/R model. Functionally, the activation of ALDH2 resulted in the improvement of cardiac hemodynamic parameters and myocardial injury, which were abolished by the treatment of Daidzin, a specific inhibitor of ALDH2. In H9C2 cardiomyocyte hypoxia-reoxygenation model, ALDH2 regulated the dynamic balance of mitochondrial fusion and fission and maintained mitochondrial morphology stability. Meanwhile, ALDH2 reduced mitochondrial ROS levels, and apoptotic protein expression in cardiomyocytes, which was associated with the upregulation of phosphorylation (p-PI3KTyr458, p-AKTSer473, p-mTOR). Moreover, ALDH2 suppressed the mitoPTP opening through reducing 4-HNE. Therefore, our results demonstrated that ALDH2 alleviated the ischemia and reperfusion injury in diabetic cardiomyopathy through inhibition of mitoPTP opening and activation of PI3K/AKT/mTOR pathway.
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Diabetes Mellitus , Cardiomiopatias Diabéticas , Traumatismo por Reperfusão Miocárdica , Ratos , Animais , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Aldeído-Desidrogenase Mitocondrial/genética , Aldeído-Desidrogenase Mitocondrial/metabolismo , Cardiomiopatias Diabéticas/genética , Cardiomiopatias Diabéticas/metabolismo , Dinâmica Mitocondrial/genética , Miócitos Cardíacos/metabolismo , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Traumatismo por Reperfusão Miocárdica/metabolismo , Isquemia/metabolismo , Apoptose , Diabetes Mellitus/metabolismoRESUMO
Predation is widely recognized as a powerful selective pressure on primate behavior and ecology, although knowledge of predator-prey relationships remains limited partly due to the rarity of directly observed attacks on primates. Here, we describe four confirmed or suspected instances of leopard (Panthera pardus) predation on free-ranging Sichuan (golden) snub-nosed monkeys (Rhinopithecus roxellana), a highly endangered colobine species endemic to China. We recorded predation events and the reactions of monkey group members. We suggest that the evolution of a multilevel society may be an adaptive response by Sichuan snub-nosed monkeys to the risk from leopards as well as other potential predators, one that balances the pressures of predation and intra-species competition and conflict.
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Colobinae , Panthera , Presbytini , Animais , Comportamento Predatório , Colobinae/fisiologia , ChinaRESUMO
OBJECTIVE: To investigate the effect of recombinant staphylokinase (r-Sak) and the Chinese medicine Yihuo Qingyi Decoction ((see test) Herbal decoction for severe acute pancreatitis) in the treatment of the severe acute pancreatitis (SAP) in rats, and to observe the synergistic effect of the two. METHODS: One hundred and sixty-two adult male SD rats with the body mass of 250-280 g were randomly divided into the following 5 groups: sham operation group (n = 18), control group (n = 36), Yihuo Qingyi Decoction treatment group (n = 36), r-Sak treatment group (n = 36), and Yihuo Qingyi Decoction plus r-Sak treatment group (n = 36). The SAP ratmodel was prepared by retrograde injection of 5% sodium taurocholate into the cholangiopancreatic duct. Two days before modeling, Yihuo Qingyi Decoction was intragastrically administrated, and r-Sak was intraperitoneally injected. The survival rate within 18 h after modeling was determined. The pancreatic blood flow, the weight of ascites, and the serum amylase and lipase were investigated at 6 h, 12 h, and 18kh after modeling, and the pancreatic tissue was examined under light microscopy to see its pathological change. RESULTS: The 18 h survival count of group A, B, C, D and E rats was 9, 2, 6, 7 and 8 respectively. After r-Sak and Yihuo Qingyi Decoction intervention, the serum amylase and lipase and the weight of ascites were significantly decreased, especially in group E.18 h after modeling, the level of the serum amylase and lipase and the weight of ascites in group E was 1 100 +/- 118 U x L(-1), 1 000 +/- 150 U x L(-1) and 13.40 +/- 1.80 g respectively, obviously lower than that of group B (P < 0.05). After SAP was induced, the pancreatic blood flow showed a tendency to decrease, but the decrease extent in the treatment groups was smaller than that in the control group. 18h after modeling, the pancreatic blood flow in group B and group E was 30.16 +/- 8.96 mL x 100 g(-1) x min(-1), and 129.10 +/- 42.58 mL x 100 g(-1) x min respectively, there was significant difference (P < 0.05). The pathological change of the pancreatic tissue was alleviated in the treatment groups. CONCLUSION: Both r-Sak and Yihuo Qingyi Decoction play a beneficial role in the treatment of rat SAP and there is a synergistic effect between the two.
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Medicamentos de Ervas Chinesas/administração & dosagem , Metaloendopeptidases/administração & dosagem , Pancreatite/tratamento farmacológico , Doença Aguda , Animais , Sinergismo Farmacológico , Masculino , Miocárdio/patologia , Pâncreas/irrigação sanguínea , Pâncreas/patologia , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes/administração & dosagemRESUMO
BACKGROUND: Syphilis cases have risen in many parts of China, with developed regions reporting the greatest share of cases. Since syphilis increases in these areas are likely driven by both increased screening and changes in sexual behaviours, distinguishing between these two factors is important. Examining municipal-level primary syphilis cases with spatial analysis allows a more direct understanding of changing sexual behaviours at a more policy-relevant level. METHODS: In this study we examined all reported primary syphilis cases from Guangdong Province, a southern province in China, since the disease was first incorporated into the mandatory reporting system in 1995. Spatial autocorrelation statistics were used to correlate municipal-level clustering of reported primary syphilis cases and gross domestic product (GDP). RESULTS: A total of 52,036 primary syphilis cases were reported over the period 1995-2008, and the primary syphilis cases increased from 0.88 per 100,000 population in 1995 to 7.61 per 100,000 in 2008. The Pearl River Delta region has a disproportionate share (44.7%) of syphilis cases compared to other regions. Syphilis cases were spatially clustered (p = 0.01) and Moran's I analysis found that syphilis cases were clustered in municipalities with higher GDP (p = 0.004). CONCLUSIONS: Primary syphilis cases continue to increase in Guangdong Province, especially in the Pearl River Delta region. Considering the economic impact of syphilis and its tendency to spatially cluster, expanded syphilis testing in specific municipalities and further investigating the costs and benefits of syphilis screening are critical next steps.
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Desenvolvimento Econômico , Sífilis/prevenção & controle , Adolescente , Adulto , China/epidemiologia , Notificação de Doenças , Feminino , Humanos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Vigilância da População , Atenção Primária à Saúde , Sífilis/epidemiologia , Sífilis/transmissão , Adulto JovemRESUMO
BACKGROUND: Psoriasis is a common inflammatory skin disease. Abnormal proliferation of keratinocytes is one of the psoriatic histopathological features. Indirubin has an essential effect on the proliferation and activation of keratinocytes; however, in psoriasis, the specific mechanism of action of indirubin on keratinocytes is unclear. In the present study, we revealed the effects of indirubin on DNA methyltransferase 1 (DNMT1), wnt inhibitory factor 1 (wif-1), and wnt/ß-catenin signal pathway, in the meantime, we explored the effects of indirubin on proliferation, cell cycle and the apoptosis of HaCaT cells. METHODS: The expression of DNMT1, wif-1, Frizzled2, Frizzled5, and ß-catenin in HaCaT cells treated with different concentrations of indirubin were detected by Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR). The expression levels of DNMT1 and wif-1 were observed after treated with different concentrations of indirubin by enzyme-linked immunosorbent assay (ELISA). The wif-1 promoter methylation status was detected by DNA methylation-specific PCR (MSP). The transcriptional activities of wif-1 and ß-catenin were discovered by a luciferase reporter gene system. Cell viability was determined by Cell Counting Kit-8 (CCK8) method. The cell cycle was detected by flow cytometry. The apoptotic cells were surveyed by the apoptosis kit. The expression of Inolucrin, Loricrin, Filaggrin, Keratin 17, and transcriptional activation of transglutaminase 1(TGase1) were detected by Western blotting. RESULTS: Indirubin inhibited the expression of DNMT1 and the methylation of the wif-1 promoter. In the wnt signal pathway, indirubin restored the protein expression of wif-1 and inhibited expression of Frizzled2, Frizzled5, and ß-catenin. Besides, indirubin inhibited the proliferation of HaCaT cells, induced apoptosis, and arrest cell cycle. We also reported that indirubin could down-regulate the expression of Involucrin, TGase 1, and keratin 17, but the expression of Filaggrin and Loricrin had no significant effect. CONCLUSION: Our research showed that indirubin promoted the demethylation of wif-1 and suppressed the wnt/ß-catenin signal pathway, thereby exerted an anti-proliferative effect. This study reveals the anti-proliferation mechanism of indirubin, which may provide an effective option for the treatment of proliferative diseases.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , DNA (Citosina-5-)-Metiltransferase 1/metabolismo , Psoríase/tratamento farmacológico , Via de Sinalização Wnt/efeitos dos fármacos , beta Catenina/metabolismo , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Proteínas Filagrinas , Células HaCaT , Humanos , Indóis/farmacologiaRESUMO
BACKGROUD: Follicular dendritic cell (FDC) sarcomas are rare neoplasms that occur predominantly in the lymph nodes. They can also occur extranodally. Extranodal FDC sarcomas most commonly present as solitary masses. Inflammatory pseudotumor (IPT)-like FDC sarcomas, a subcategory of FDC sarcomas, are rarer than other sarcoma subtypes. They are composed of spindle or ovoid neoplastic cells and exhibit an admixture of plasma cells and prominent lymphoplasmacytic infiltration. Paraneoplastic pemphigus (PNP), also known as paraneoplastic autoimmune multiorgan syndrome, is a rare autoimmune bullous disease that is associated with underlying neoplasms. PNP has a high mortality, and its early diagnosis is usually difficult. CASE SUMMARY: We describe a 27-year-old woman who presented with stomatitis, conjunctivitis, and skin blisters and erosions as her first symptoms of PNP with an intra-abdominal IPT-like FDC sarcoma. The patient underwent surgical tumor resection and received tapering oral corticosteroid treatment. She showed no recurrence at the 1-year follow-up. CONCLUSION: IPT-like FDC sarcomas are rare underlying neoplasms that have an uncommon association with PNP. PNP-associated FDC sarcomas predominantly occur in intra-abdominal sites and suggest a poor prognosis. Surgical resection is an essential and effective treatment for PNP and primary and recurrent FDC sarcomas.
RESUMO
OBJECTIVE: To study the effect of Weiganli on the level of FL in bone marrow and serum of myelosuppressed anemic mice, and to explore it's function on hematopoietic regulation. METHOD: Models of myelosuppressed anemic mice were induced by radiation and chemotherapeutic drug, and the mice were randomly divided into normal group, myelosuppressed anemic group, and Weiganli group (high dose 100 g x L(-1), medium dose 50 g x L(-1), low dose 25 g x L(-1)). Effect of Weiganli on the number of the peripheral blood cells and bone marrow nucleated cells (BMC) were evaluated. Effect of Weiganli on the level of FL (Flt3 ligand) was investigated by ELISA technique. RESULT: High dose of Weiganli could significantly increase granulocytes, erythrocytes, Hb and BMC, while both the medium dose and the low dose had more significant action in increase of platelet. The level of FL in bone marrow and serum were lower in Weiganli group than that in myelosuppressed anemic group, especially in high and medium dose group. CONCLUSION: The myelosuppresion of mice which induced by radiation and chemotherapeutic drug could be significantly relieved by Weiganli.