RESUMO
Professor Rajeev K. Varshney's transformative impact on crop genomics, genetics, and agriculture is the result of his passion, dedication, and unyielding commitment to harnessing the potential of genomics to address the most pressing challenges faced by the global agricultural community. Starting from a small town in India and reaching the global stage, Professor Varshney's academic and professional trajectory has inspired many scientists active in research today. His ground-breaking work, especially his effort to list orphan tropical crops to genomic resource-rich entities, has been transformative. Beyond his scientific achievements, Professor Varshney is recognized by his colleagues as an exemplary mentor, fostering the growth of future researchers, building institutional capacity, and strengthening scientific capability. His focus on translational genomics and strengthening seed system in developing countries for the improvement of agriculture has made a tangible impact on farmers' lives. His skills have been best utilized in roles at leading research centres where he has applied his expertise to deliver a new vision for crop improvement. These efforts have now been recognized by the Royal Society with the award of the Fellowship (FRS). As we mark this significant milestone in his career, we not only celebrate Professor Varshney's accomplishments but also his wider contributions that continue to transform the agricultural landscape.
Assuntos
Produtos Agrícolas , Genômica , Retratos como Assunto , Agricultura/história , Produtos Agrícolas/genética , Genômica/história , História do Século XX , História do Século XXI , Retratos como Assunto , Sociedades Científicas/organização & administraçãoRESUMO
Nontuberculous mycobacteria (NTM) is a large group of mycobacteria other than the Mycobacterium tuberculosis complex and Mycobacterium leprae. Epidemiological investigations have found that the incidence of NTM infections is increasing in China, and it is naturally resistant to many antibiotics. Therefore, studies of NTM species in clinical isolates are useful for understanding the epidemiology of NTM infections. The present study aimed to investigate the incidence of NTM infections and types of NTM species. Of the 420 samples collected, 285 were positive for M. tuberculosis, 62 samples were negative, and the remaining 73 samples contained NTM, including 35 (8.3%) only NTM and 38 (9%) mixed (M. tuberculosis and NTM). The most prevalent NTM species were Mycobacterium intracellulare (30.1%), followed by Mycobacterium abscessus (15%) and M. triviale (12%). M. gordonae infection was detected in 9.5% of total NTM-positive cases. Moreover, this study reports the presence of Mycobacterium nonchromogenicum infection and a high prevalence of M. triviale for the first time in Henan. M. intracellulare is the most prevalent, accompanied by some emerging NTM species, including M. nonchromogenicum and a high prevalence of M. triviale in Henan Province. Monitoring NTM transmission and epidemiology could enhance mycobacteriosis management in future.
Assuntos
Infecções por Mycobacterium não Tuberculosas , Micobactérias não Tuberculosas , China/epidemiologia , Micobactérias não Tuberculosas/isolamento & purificação , Micobactérias não Tuberculosas/classificação , Humanos , Infecções por Mycobacterium não Tuberculosas/epidemiologia , Infecções por Mycobacterium não Tuberculosas/microbiologia , Prevalência , Pessoa de Meia-Idade , Masculino , Feminino , Adulto , Idoso , Adulto Jovem , Adolescente , Idoso de 80 Anos ou mais , Criança , IncidênciaRESUMO
Paclitaxel (PTX) is a chemotherapeutic agent that is widely used for the treatment of several types of tumors. However, PTX-induced peripheral neuropathy (PIPN) is an adverse effect generally induced by long-term PTX use that significantly impairs the quality of life. Necroptosis has been implicated in various neurodegenerative disorders. Necroptosis of dorsal root ganglion neurons triggers the pathogenesis of PIPN. Therefore, the present study aims to investigate the role of spinal neuronal necroptosis in PIPN. It also explores the potential role of microglial polarization in necroptosis. We established rat models of PIPN via quartic PTX administration on alternate days (accumulated dose: 8 mg/kg). PTX induced obvious neuronal necroptosis and upregulated the expression of receptor-interacting protein kinase (RIP3) and mixed lineage kinase domain-like protein (MLKL) in the spinal dorsal horn. These effects were inhibited with a necroptosis pathway inhibitor, necrostatin-1 (Nec-1). The effect of microglial polarization on the regulation of spinal necroptosis was elucidated by administering minocycline to inhibit PTX-induced M1 polarization of spinal microglia caused by PTX. We observed a significant inhibitory effect of minocycline on PTX-induced necroptosis in spinal cord cells, based on the downregulation of RIP3 and MLKL expression, and suppression of tumor necrosis factor-α and IL-ß synthesis. Additionally, minocycline improved hyperalgesia symptoms in PIPN rats. Overall, this study suggests that PTX-induced polarization of spinal microglia leads to RIP3/MLKL-regulated necroptosis, resulting in PIPN. These findings suggest a potential target for the prevention and treatment of neuropathic pain.
Assuntos
Neuralgia , Paclitaxel , Ratos , Animais , Paclitaxel/efeitos adversos , Microglia/patologia , Necroptose , Minociclina/efeitos adversos , Qualidade de Vida , Neuralgia/induzido quimicamenteRESUMO
Hepatocellular carcinoma (HCC) represents an estrogen-dependent tumor. The action of estrogen is regulated via estrogen receptor (ER). Polymorphisms in ERα gene, ESR1, are known to be related to HCC susceptibility among people carrying chronic hepatitis B (CHB). But the effect of ERß on HCC is still largely unclear, and studies about the genetic variability of ESR2 and HCC are rare. For understanding ESR2's effect on HCC, this work tested two polymorphisms in the ESR2 gene promoter as well as the associations with CHB, HCC, and hepatitis B virus (HBV)-related liver cirrhosis (LC) among the Guangxi population. This work enrolled a total of 137 CHB, 136 LC, and 149 HBV-related HCC patients, together with 146 normal subjects. ESR2 polymorphisms rs3020449 and rs2978381 were examined using the SNaPshot genotyping technique. The AG genotype and dominant model of rs3020449 were related to the decreased CHB susceptibility. In both the overall and subgroup analyses, no associations were observed with the remaining models in all patient groups (those with CHB, HBV-related LC, and HCC), but associations were found between the dominant (TC+CC vs TT) and allele models (C vs T) of rs2978381 and increased HBV-related LC and HCC susceptibility, but not CHB. These findings suggest that rs3020449 polymorphism of ESR2 gene makes great contribution to the decreased CHB risk and that rs2978381 significantly contributed to higher risks of HBV-related LC and HCC.
RESUMO
Rubella, a viral disease characterized by a red skin rash, is well controlled because of an effective vaccine, but outbreaks are still occurring in the absence of available antiviral treatments. The Rubella virus (RUBV) papain-like protease (RubPro) is crucial for RUBV replication, cleaving the nonstructural polyprotein p200 into two multifunctional proteins, p150 and p90. This protease could represent a potential drug target, but structural and mechanistic details important for the inhibition of this enzyme are unclear. Here, we report a novel crystal structure of RubPro at a resolution of 1.64 Å. The RubPro adopts a unique papain-like protease fold, with a similar catalytic core to that of proteases from Severe acute respiratory syndrome coronavirus 2 and foot-and-mouth disease virus while having a distinctive N-terminal fingers domain. RubPro has well-conserved sequence motifs that are also found in its newly discovered Rubivirus relatives. In addition, we show that the RubPro construct has protease activity in trans against a construct of RUBV protease-helicase and fluorogenic peptides. A protease-helicase construct, exogenously expressed in Escherichia coli, was also cleaved at the p150-p90 cleavage junction, demonstrating protease activity of the protease-helicase protein. We also demonstrate that RubPro possesses deubiquitylation activity, suggesting a potential role of RubPro in modulating the host's innate immune responses. We anticipate that these structural and functional insights of RubPro will advance our current understanding of its function and help facilitate more structure-based research into the RUBV replication machinery, in hopes of developing antiviral therapeutics against RUBV.
Assuntos
Peptídeo Hidrolases , Vírus da Rubéola , Motivos de Aminoácidos , Papaína/química , Peptídeo Hidrolases/química , Peptídeo Hidrolases/metabolismo , Dobramento de Proteína , Estrutura Terciária de Proteína , Vírus da Rubéola/química , Vírus da Rubéola/enzimologiaRESUMO
OBJECTIVE: We performed a systematic review and meta-analysis to analyze the efficacy and safety of sirolimus-eluting stents (SESs) in the treatment of below-the-knee (BTK) arterial disease. METHODS: An electronic literature search was conducted from inception to July 24, 2021. Retrospective, prospective, and randomized studies that had used SESs to treat BTK arterial disease and had reported the primary patency, technical success, target lesion revascularization, and/or mortality were included. Meta-analyses of the proportions were conducted to derive pooled summary statistics of the outcomes. Where Kaplan-Meier curves were provided for primary patency, a meta-analysis of the individual patient data was conducted via a graphic reconstruction tool to estimate primary patency at various follow-up points. For studies comparing SESs and bare metal stents (BMSs), a two-stage meta-analysis was performed to compare the 6-month primary patency of SESs vs BMSs. RESULTS: Ten studies across 13 publications, including 995 patients, were retrieved for analysis. In the meta-analysis of proportions, across six studies (n = 339 patients), the pooled 6-month primary patency was 87.3% (95% confidence interval [CI], 81.6%-92.1%). Across seven studies (n = 283 patients), the pooled 6-month mortality was 5.4% (95% CI, 1.4%-11.2%). An individual patient data analysis of three studies (n = 282 patients) yielded a primary patency rate of 95.2% (95% CI, 92.7%-97.8%), 82.8% (95% CI, 78.3%-87.6%), 79.8% (95% CI, 75.0%-85.0%), and 79.8% (95% CI, 75.0%-85.0%) at 6, 12, 18, and 24 months, respectively. The 12-month target lesion revascularization rate across four studies (n = 324 patients) was 9.6% (95% CI, 6.4%-13.4%). In the two-stage meta-analysis of 6-month primary patency across three studies (n = 168 patients), the use of SESs was significantly favored over BMSs (risk ratio, 1.28; 95% CI, 1.12-1.46; P < .001). CONCLUSIONS: The overall evidence suggests that the use of SESs appears to be safe and offers favorable outcomes for BTK arterial disease compared with BMSs.
Assuntos
Stents Farmacológicos , Sirolimo , Doenças Vasculares , Humanos , Stents Farmacológicos/efeitos adversos , Estudos Prospectivos , Estudos Retrospectivos , Sirolimo/administração & dosagem , Sirolimo/uso terapêutico , Stents/efeitos adversos , Resultado do Tratamento , Doenças Vasculares/terapiaRESUMO
BACKGROUND: Transcultural capacity is a key component of consolidated global public health assistance cooperation (GPHAC). The aim of this study is to investigate the transcultural capacity perceptions of public health professionals from China's disease control and prevention system after relative training in order to provide a reference for enhancing transcultural capacity during the practice of GPHAC. METHODS: A cross sectional qualitative survey in which self-administrated questionnaire with 5 open ended questions was used. The questionnaire was disseminated on the completion of an online training for China's senior public health professions on transcultural capacity in GPHAC. Descriptive statistics, word frequency analysis and content analysis were used to analyze the questionnaire data. RESULTS: Totally, 45 participants took part in this training, 25 of them voluntarily participated in this survey. The participants demonstrated the need for transcultural competence in public health services and suggested improvement in the course content arising from their wealth of knowledge and practical experience in the field. 96% of the participants considered that the training course was "very necessary" and "meaningful". The most interested topics were "Overview of transcultural adaptation and GPHAC", "Transcultural adaptation and response" and "African culture and health". The contents about "Country-specific analysis on cultural factors in public health", "rapid transcultural adaptation" and "more specific practical experiences in diverse cultural backgrounds" were suggested to be added in future training. The participants considered that transcultural capacity ensured the smooth progress of GPHAC and they both could complement each other, transcultural adaptation was the premise of gaining trust and reaching cooperation, it can be conducive to the health assistance professionals to integrate into local cultural life, facilitating their foreign assistance work to be effective and efficient, and impart experiences well. The participants hoped to put the concept into action. CONCLUSION: The importance of transcultural competence in GPHAC is becoming a consensus of public health professionals. Enhanced transcultural competence reflected in the attitude of public health as well as other health workers would promote GPHAC and would foster efficient emergency health response management among many countries.
Assuntos
Competência Cultural , Saúde Pública , Humanos , Competência Cultural/educação , Estudos Transversais , Pessoal de Saúde/educação , Diversidade CulturalRESUMO
OBJECTIVES: To evaluate the diagnostic efficacy of contrast-enhanced ultrasonography (CEUS) for detecting catheter-related right brachiocephalic vein (RBV) and superior vena cava (SVC) obstructions in patients undergoing hemodialysis (HD). METHODS: From June 1, 2021 to December 31, 2022, we enrolled 80 patients undergoing HD who had used or were using a central venous catheter as vascular access. We evaluated the diagnostic efficacy of conventional ultrasonography and CEUS for identifying RBV and SVC obstructions and compared them with that of digital subtraction angiography (DSA). In the stratified analysis, the SVC was divided into the upper and lower segments. In total, we analyzed 240 central venous segments, including the RBV. RESULTS: Among the RBV and SVC visualized by DSA, conventional ultrasonography and CEUS could visualize 67.92 and 100% of the vein segments, respectively; however, the lengths and diameters of the RBV and SVC were smaller than those recorded with DSA (P < .001). The diagnostic efficacy of CEUS for detecting catheter-related central venous obstruction was better than that of conventional ultrasonography, with a higher sensitivity (83.95 vs 41.98%), specificity (89.94 vs 53.46%), accuracy (87.92 vs 49.58%), and F1 score (82.42 vs 49.64%). CEUS showed good agreement (κ = 0.732) with DSA. In the stratified analyses, CEUS also showed higher sensitivity (83.93, 83.33, and 84.62%, respectively) and better agreement with DSA (κ = 0.635, 0.655, and 0.673, respectively) than conventional ultrasonography for detecting the RBV and the upper and lower segments of the SVC. CONCLUSIONS: CEUS had high sensitivity and specificity in diagnosing catheter-related RBV and SVC obstructions.
Assuntos
Cateteres Venosos Centrais , Síndrome da Veia Cava Superior , Humanos , Veia Cava Superior/diagnóstico por imagem , Veias Braquiocefálicas/diagnóstico por imagem , Síndrome da Veia Cava Superior/diagnóstico por imagem , Síndrome da Veia Cava Superior/etiologia , Síndrome da Veia Cava Superior/patologia , Projetos Piloto , Ultrassonografia , Diálise Renal/efeitos adversos , Cateteres Venosos Centrais/efeitos adversosRESUMO
Colony-stimulating factors (CSFs) are glycoproteins that stimulate the proliferation and differentiation of hematopoietic progenitor cells in the bone marrow. But numerous studies have shown that these factors can stimulate the proliferation of non-hematopoietic cells, including cancer cells. Hence, in this study, Macrophage-CSF (M-CSF), macrophage-granulocyte CSF (GM-CSF), and granulocyte-SCF (G-CSF) were evaluated in the serum of patients with breast tumors and their relationship with pathological and paraclinical parameters of the disease. In this study, 62 patients with breast cancer who had not received any treatment and 54 healthy women who matched the age group with the patient group were included as a control group. After obtaining informed consent, 5ml of peripheral blood was taken from both groups, and their serum was isolated. Serum levels of the studied cytokines were measured by the cytokine-bead array method. Data were analyzed using SPSS18 software and a significance level of 0.05. The mean serum levels of M-CSF, G-CSF, and GM-CSF growth factors in patients with breast cancer were 63.48, 16.13, and 6.11pg/ml, respectively. Although the statistical analysis did not show a significant difference between serum levels of these growth factors in the patient and control groups (p <0.05), further studies showed that with increasing disease stages from I to III, serum levels of GM-CSF significantly. Decreases (p = 0.016). Overall, the results of this study indicated the antitumor role of GM-CSF in breast cancer. However, confirmation of these results requires more complete studies with larger sample sizes.
Assuntos
Neoplasias da Mama , Fator Estimulador de Colônias de Granulócitos e Macrófagos , Fatores Estimuladores de Colônias , Citocinas , Feminino , Fator Estimulador de Colônias de Granulócitos , Granulócitos , Humanos , Fator Estimulador de Colônias de Macrófagos , MacrófagosRESUMO
BACKGROUND: This study was a randomized controlled trial to evaluate efficacy and safety of the usage of intravenous tranexamic acid during posterior operation of multilevel thoracic spine stenosis for controlling perioperative blood loss. METHODS: Sixty eight patients with multilevel thoracic spine stenosis were randomized into the tranexamic acid group receiving 15 mg/kg body weight before the skin incision was made and 1 mg/kg body weight per hour during operation or the control group receiving the same dose of placebo (0.9% sodium chloride solution) intravenously. Pedicle screw fixation, laminectomy and selective discectomy were performed. Intraoperative and perioperative total blood loss were compared. The necessity and amount for blood transfusion, blood coagulation function, durations of postoperative hospital stays were compared. The complications of tranexamic acid were also investigated such as cardiovascular and cerebrovascular events, lower limb venous thrombosis. RESULTS: There were no statistically significant differences in age, gender, body mass index, ASA status, pathology required surgery, preoperative hemoglobin, operation time, laminectomy segments and discectomy segments between the tranexamic acid and control groups. The intraoperative blood loss (455.9 ± 206.6 ml vs 580.6 ± 224.3 ml, p < 0.05) and total blood loss (675.3 ± 170.3 ml vs 936.8 ± 306.4 ml, p < 0.01) in tranexamic acid group were significant lower than those in control group. The means of blood unit transfused (2.5 ± 1.0 vs 4.7 ± 2.4, p < 0.05) and Hb reduction in 48 h (22.5 ± 3.4 g/L vs 25.3 ± 3.9 g/L, p < 0.01) were significantly lower in tranexamic acid group than that in control group. There were no statistically significant differences in blood coagulation function pre-operation or 48 h post-operation between the tranexamic acid and the control groups. The requirements for patients to receive blood transfusion were fewer and durations of post-operational hospital stays were shorter in the tranexamic acid group, however, the difference did not achieve statistical significance. There was no significant difference in superficial or deep venous thrombosis of lower limbs or deterioration of neurological function between tranexamic acid group and control group. CONCLUSIONS: Application of intravenous tranexamic acid significantly reduces intraoperative and perioperative total blood loss without significant side effects in posterior operation of multilevel thoracic spine stenosis. TRIAL REGISTRATION: At Chinese Clinal Trial Registry. http://www.chictr.org.cn/ , ChiCTR2100054221. Registered on 11/12/2021.
Assuntos
Antifibrinolíticos , Estenose Espinal , Ácido Tranexâmico , Peso Corporal , Constrição Patológica/induzido quimicamente , Constrição Patológica/tratamento farmacológico , Humanos , Estudos Prospectivos , Estenose Espinal/cirurgia , Resultado do TratamentoRESUMO
In this Letter, we introduce a new class of angular dependent autofocusing ring Pearcey beams by imposing a cross-phase structure. Due to this structure, the beam exhibits a non-uniform abrupt autofocusing behavior. Unlike the properties of the ring Pearcey beam without a cross phase [Opt. Lett.43, 3626 (2018)OPLEDP0146-959210.1364/OL.43.003626], we can flexibly adjust the focal length of the beam and its focusing ability, as well as the direction of the ring Pearcey beams, with the help of only the cross-phase structure. Furthermore, the Poynting vectors are employed to demonstrate convincingly the beam-focusing mechanism. Such beams with these fascinating characteristics are anticipated to find potential applications in optical tweezing, three-dimensional printing, material processing, and so on.
RESUMO
This paper was aimed to explore the potential pharmacodynamics effect of Euonymus alatus in the treatment of nephritis based on integrated chemomics and network biology. The chemical constituent database of E. alatus was constructed by consulting litera-ture and using online database. The chemical constituents were identified by UPLC-Q-TOF/HRMS~E and UNIFI software. On this basis, a series of comparisons, molecular docking studies and in-depth analysis of the chemical constituents and nephritis disease targets were carried out with use of network biology method, and the potential pharmacodynamic effect of E. alatus for the treatment of nephritis was investigated by reviewing the existing. In this study, 62 chemical constituents were collected in the database of chemical consti-tuents of E. alatus, and 24 chemical constituents were identified by mass spectrum. Subsequently, based on the network biology me-thod, 22 important chemical constituents and 5 key targets were obtained by reverse screening. Molecular docking study showed that a total of 11 chemical constituents such as quercetin, kaempferol, and catechinmay be the potential material basis for E. alatus in the treatment of nephritis. Starting with chemomics and using the technology of network biology, we established a network interaction model between drug components and disease targets in this study. Through the interaction between targets in complex networks, we can find the key targets easily and quickly. By docking the key targets with small drug molecules, we can screen out the potential pharmacodynamic components, providing a reference for the follow-up study of active ingredients.
Assuntos
Euonymus , Nefrite , Seguimentos , Humanos , Simulação de Acoplamento Molecular , QuercetinaRESUMO
Syringa pinnatifolia is an endemic species of Syringa in Oleaceae family in China, mainly distributed in Helan Mountain, which is located between Inner Mongolia and Ningxia. Its peeled roots, stems and thick twigs have been used as Mongolian folk medicine, called "Shan-chen-xiang" in Chinese, for the treatment of coronary heart diseases, angina pectoris and other cardiopulmonary diseases. Modern researches showed that S. pinnatifolia mainly contains lignans, sesquiterpenoids, and volatile oils, and displays anti-myocardial ischemia, sedation, analgesia, antibacterial and other effects. In the past five years, many groups have made new progress on the study of chemical constituents and pharmacological activities of S. pinnatifolia. On the basis of the previous review by our group, this paper summarizes the advances which is beneficial to the development, research and clinical application of S. pinnatifolia, particularly Shan-chen-xiang.
Assuntos
Oleaceae , Syringa , China , Medicina Tradicional da Mongólia , Compostos Fitoquímicos/farmacologiaRESUMO
Ascochyta blight (AB) is one of the major biotic stresses known to limit the chickpea production worldwide. To dissect the complex mechanisms of AB resistance in chickpea, three approaches, namely, transcriptome, small RNA and degradome sequencing were used. The transcriptome sequencing of 20 samples including two resistant genotypes, two susceptible genotypes and one introgression line under control and stress conditions at two time points (3rd and 7th day post inoculation) identified a total of 6767 differentially expressed genes (DEGs). These DEGs were mainly related to pathogenesis-related proteins, disease resistance genes like NBS-LRR, cell wall biosynthesis and various secondary metabolite synthesis genes. The small RNA sequencing of the samples resulted in the identification of 651 miRNAs which included 478 known and 173 novel miRNAs. A total of 297 miRNAs were differentially expressed between different genotypes, conditions and time points. Using degradome sequencing and in silico approaches, 2131 targets were predicted for 629 miRNAs. The combined analysis of both small RNA and transcriptome datasets identified 12 miRNA-mRNA interaction pairs that exhibited contrasting expression in resistant and susceptible genotypes and also, a subset of genes that might be post-transcriptionally silenced during AB infection. The comprehensive integrated analysis in the study provides better insights into the transcriptome dynamics and regulatory network components associated with AB stress in chickpea and, also offers candidate genes for chickpea improvement.
Assuntos
Ascomicetos , Cicer/genética , Resistência à Doença/genética , MicroRNAs/genética , Doenças das Plantas/microbiologia , RNA de Plantas/genética , Transcriptoma/genética , Cicer/imunologia , Cicer/metabolismo , Cicer/microbiologia , Regulação da Expressão Gênica de Plantas , Estudos de Associação Genética , Doenças das Plantas/imunologia , Locos de Características Quantitativas/genética , Análise de Sequência de RNARESUMO
The development of optical thermometers operating within the first biological window (650-1000 nm) has drawn great interest lately in the biological and medical fields. Here a new type of luminescent thermometer relying on the intensity ratio between G41-F43 (652 nm) and F2,33-H63(691 nm) transitions in Tm3+/Yb3+:BaMoO4 phosphor is reported under 980 nm excitation. The thermometry is found to be independent on the excitation power, benefiting the reduction of the measurement error. Moreover, it exhibits extremely high absolute sensitivity ranging from 210.5×10-4 to 1034.5×10-4 K-1 in 298-498 K. The maximal relative sensitivity and temperature resolutions (1.36% K-1 and 0.37 K, respectively) are also among the highest values of those previous thermometric materials. This Letter provides guidance in selecting the suitable emission bands to construct the ratiometric luminescent thermometers with high performance.
Assuntos
Bário/química , Luminescência , Molibdênio/química , Termometria/métodos , Túlio/química , Itérbio/química , TemperaturaRESUMO
Mantle cell lymphoma (MCL) is an uncommon and typically aggressive form of lymphoma. Although often initially chemosensitive, relapse is common. Several induction and conditioning regimens are used in transplant-eligible patients, and the optimal approach remains unknown. We performed an international, retrospective study of transplant-eligible patients to assess impact of induction chemoimmunotherapy and conditioning regimens on clinical outcomes. We identified 228 patients meeting inclusion criteria. Baseline characteristics were similar among the induction groups except for some variation in age. The type of induction chemoimmunotherapy received did not influence overall response rates (ORRs) (0.43), progression-free survival (PFS) (P > .67), or overall survival (OS) (P > .35) on multivariate analysis (PFS and OS). Delivery of autologous stem cell transplant (ASCT) was associated with favorable PFS and OS (0.01) on univariate analysis only; this benefit was not seen on multivariate analysis-PFS (0.36) and OS (0.21). Compared with busulfan and melphalan (BuMel), the use of the carmustine, etoposide, cytarabine, melphalan (BEAM)-conditioning regimen was associated with inferior PFS (HR = 2.0 [95% CI 1.1-3.6], 0.02) but not OS (HR = 1.1 [95% CI 0.5-2.3], 0.81) on univariate analysis only. Within the limits of a retrospective study and modest power for some comparisons, type of induction therapy did not influence ORR, PFS, or OS for transplant-eligible patients with MCL. International efforts are required to perform randomized clinical trials evaluating chemoimmunotherapy induction regimens.
Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Imunoterapia/métodos , Quimioterapia de Indução/métodos , Linfoma de Célula do Manto/terapia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carmustina/uso terapêutico , Citarabina/uso terapêutico , Progressão da Doença , Intervalo Livre de Doença , Etoposídeo/uso terapêutico , Feminino , Humanos , Cooperação Internacional , Linfoma de Célula do Manto/mortalidade , Masculino , Melfalan/uso terapêutico , Pessoa de Meia-Idade , Análise Multivariada , Recidiva Local de Neoplasia/tratamento farmacológico , Indução de Remissão , Estudos Retrospectivos , Condicionamento Pré-Transplante , Resultado do TratamentoRESUMO
PURPOSE: To investigate the effect of 4-phenylbutyric acid (4-PBA) on intermittent hypoxia (IH)-induced liver cell injury and to clarify the underlying mechanisms. METHODS: L02 cells (normal human liver cells) were cultured in normoxic condition or subjected to intermittent hypoxia for 4, 8, and 12 h. A part of hypoxia-treated L02 cells was applied with 4-PBA 1 h before exposure to hypoxia. The effect of 4-PBA on liver injury, hepatocyte apoptosis, endoplasmic reticulum stress (ERS), and PERK-eIFa2-ATF4-CHOP apoptotic pathway was investigated. RESULTS: (1) IH caused apoptosis in hepatocyte; (2) IH caused ERS in hepatocyte; (3) IH caused hepatic injury; (4) 4-PBA attenuated IH-induced liver cell injury; (5) 4-PBA protected liver cell from IH-induced apoptosis; (6) 4-PBA suppressed ERS-related apoptotic pathway (PERK-eIFa2-ATF4-CHOP), but did not suppress IH-induced unfold protein reaction (UPR). CONCLUSIONS: 4-PBA could protect liver cells by suppressing IH-induced apoptosis mediated by ERS, but not by reducing the UPR.
Assuntos
Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Retículo Endoplasmático/efeitos dos fármacos , Retículo Endoplasmático/fisiologia , Hepatócitos/efeitos dos fármacos , Hepatócitos/fisiologia , Hipóxia/complicações , Hipóxia/fisiopatologia , Fenilbutiratos/farmacologia , Sobrevivência Celular/fisiologia , Células Cultivadas , Humanos , Resposta a Proteínas não Dobradas/efeitos dos fármacosRESUMO
Despite of the fact that engine manufacturers develop a new technology to reduce exhaust emissions, insufficient attention given to particulate emissions. However, diesel exhaust particles are a major source of air-borne pollution, contain vast amount of polycyclic aromatic hydrocarbons (PAHs) and may have deleterious effects on the immune system, resulting in the induction and enhancement of pro-allergic processes. In the current study, vehicle emitted particles (VEP) from 2 different types of cars (diesel - D and gasoline - G) and locomotive (L) were collected. Overall, 129 four-week-old, male SPF-class Kunming mice were subcutaneously instilled with either low dose 100, 250 or high dose, 500mg/kg VEP and 15 mice were assigned as control group. The systemic toxicity was evaluated and alterations in the percentages of the CD3, CD4, CD8, CD16, CD25 expressing cells, basophils, eosinophils and neutrophils were determined. Basophil percentages were inversely associated with the PAH content of the VEPs, however basophil sensitization was more important than cell count in VEP exposure. Thus, the effects of VEP-PAHs emerge with the activation of basophils in an allergen independent fashion. Despite the increased percentage of CD4+ T cells, a sharp decrease in basophil counts at 500mg/kg of VEP indicates a decreased inhibitory effect of CD16+ monocytes on the proliferation of CD4+ T cell and suppressed polarization into a Th2 phenotype. Therefore, although the restrictions for vehicles emissions differ between countries, follow up studies and strict regulations are needed.
Assuntos
Poluentes Atmosféricos/toxicidade , Basófilos/efeitos dos fármacos , Basófilos/imunologia , Inflamação/imunologia , Material Particulado/toxicidade , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Emissões de Veículos/toxicidade , Animais , Automóveis , Inflamação/induzido quimicamente , Masculino , Camundongos , Federação Russa , Organismos Livres de Patógenos EspecíficosRESUMO
PURPOSE: The purpose of this study was to analyze the imaging findings and clinical features of intracal lymphoplasmacyte-rich meningioma. PATIENTS AND METHODS: The clinical, radiographic, and pathological data of 9 patients of lymphoplasmacyte-rich meningioma were analyzed retrospectively. RESULTS: All cases were solitary; 8 patients with headache, dizziness, and vomiting; 2 patients with vision loss and one with progressive hearing loss; and 4 cases of secondary anemia, 3 of them with secondary hyperplasia of polyclonal immunoglobulin. In the plain CT scan of 6 cases, all masses showed higher density and without clear boundary, and 5 masses accompany obvious peritumoral edema. In plain MRI scan, all of the tumors appeared with irregular shape and unclear boundaries, 8 of the masses with obvious peritumoral edema. Enhanced scan showed all cases were significantly enhanced and the meninges in 7 cases thicken irregularly and extensively. The pathology showed that the tumors were irregularly shaped with grayish red or grayish white cut surfaces. Histological examination showed that the tumors consisted of abundant and diverse cells and different numbers of spindle tumor cells, and meningeal epithelial cells in the background of abundant inflammatory cells could be seen. The 9 cases all had surgery; only 1 case of recurrence in the first year after the operation was noted in the follow-up over 1 to 4 years, and no recurrence could be found after the second surgery. CONCLUSION: Lymphoplasmacyte-rich meningioma is a seldom-seen subtype meningioma of WHO grade I, often accompanying anemia or polyclonal immunoglobulin hyperplasia, which can recover to normal state after removing the masses. The masses showed higher density and without clear boundary in plain CT scan, and most of the tumors appear with irregular shape, obvious edema, and significant enhancement in the MRI scan. The prognosis is favorable after surgical resection and the recurrence rate is low.
Assuntos
Neoplasias Meníngeas/diagnóstico , Meningioma/diagnóstico , Adolescente , Adulto , Anemia/diagnóstico , Criança , Tontura/diagnóstico , Edema/diagnóstico , Feminino , Seguimentos , Cefaleia/diagnóstico , Humanos , Linfócitos/patologia , Imageamento por Ressonância Magnética/métodos , Masculino , Neoplasias Meníngeas/patologia , Neoplasias Meníngeas/cirurgia , Meningioma/patologia , Meningioma/cirurgia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Plasmócitos/patologia , Reoperação , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento , Vômito/diagnóstico , Adulto JovemRESUMO
The development of atherosclerosis (AS) is a multifactorial process, in which elevated plasma resistin (a key factor leading to insulin resistance) levels play an important role. Emerging evidence indicate that microRNAs (miRNAs) are involved in AS; However, the regulation and function of miRNAs in response to AS remain poorly understood. Our study analyzed the effects of miR-492 on insulin resistance, endothelial activation, and resistin expression in apoE knock-out mice and human umbilical vein endothelial cells after high-glucose treatment and miR-492 mimics transfection. We also investigated the underlying molecular mechanisms. Our results showed that high glucose stress induced a significant decrease in miR-492 expression, with a remarkable upregulation of resistin expression. We then identified resistin as a novel direct target of miR-492 using 3'-UTR luciferase reporter assay. Histopathologic examination demonstrated that upregulation of miR-492 attenuated endothelial cells migration and lipid accumulation induced by high glucose stress. Further investigation demonstrated that the upregulation of p-STAT3, SOCS, and P-selectin activation induced by high glucose stress was attenuated by upregulation of miR-492. Together, our findings indicate that miR-492 contributes to insulin resistance and endothelial dysfunction induced by high glucose, via directly downregulating resistin expression, and involving STAT3 phosphorylation, SOCS, and P-selectin activation.