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1.
Acta Pharmacol Sin ; 2022 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-35027662

RESUMO

Liver fibrosis is the common consequence of almost all liver diseases and has become an urgent clinical problem without efficient therapies. Recent evidence has shown that hepatocytes-derived extracellular vesicles (EVs) play important roles in liver pathophysiology, but little is known about the role of damaged hepatocytes-derived EVs in hepatic stellate cell (HSC) activation and following fibrosis. Tetramethylpyrazine (TMP) from Ligusticum wallichii Franchat exhibits a broad spectrum of biological activities including liver protection. In this study, we investigated whether TMP exerted liver-protective action through regulating EV-dependent intercellular communication between hepatocytes and HSCs. Chronic liver injury was induced in mice by CCl4 (1.6 mg/kg, i.g.) twice a week for 8 weeks. In the last 4 weeks of CCl4 administration, mice were given TMP (40, 80, 160 mg·kg-1·d-1, i.g.). Acute liver injury was induced in mice by injection of a single dose of CCl4 (0.8 mg/kg, i.p.). After injection, mice were treated with TMP (80 mg/kg) every 24 h. We showed that TMP treatment dramatically ameliorated CCl4-induced oxidative stress and hepatic inflammation as well as acute or chronic liver fibrosis. In cultured mouse primary hepatocytes (MPHs), treatment with CCl4 or acetaminophen resulted in mitochondrial dysfunction, release of mitochondrial DNA (mtDNA) from injured hepatocytes to adjacent hepatocytes and HSCs through EVs, mediating hepatocyte damage and fibrogenic responses in activated HSCs; pretreatment of MPHs with TMP (25 µM) prevented all these pathological effects. Transplanted serum EVs from TMP-treated mice prevented both initiation and progression of liver fibrosis caused by CCl4. Taken together, this study unravels the complex mechanisms underlying the protective effects of TMP against mtDNA-containing EV-mediated hepatocyte injury and HSC activation during liver injury, and provides critical evidence inspiring the development of TMP-based innovative therapeutic agents for the treatment of liver fibrosis.

2.
BMC Biol ; 20(1): 3, 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-34996429

RESUMO

BACKGROUND: Rodent ultrasonic vocalizations (USVs) are crucial to their social communication and a widely used translational tool for linking gene mutations to behavior. To maximize the causal interpretation of experimental treatments, we need to understand how neural control affects USV production. However, both the aerodynamics of USV production and its neural control remain poorly understood. RESULTS: Here, we test three intralaryngeal whistle mechanisms-the wall and alar edge impingement, and shallow cavity tone-by combining in vitro larynx physiology and individual-based 3D airway reconstructions with fluid dynamics simulations. Our results show that in the mouse and rat larynx, USVs are produced by a glottal jet impinging on the thyroid inner wall. Furthermore, we implemented an empirically based motor control model that predicts motor gesture trajectories of USV call types. CONCLUSIONS: Our results identify wall impingement as the aerodynamic mechanism of USV production in rats and mice. Furthermore, our empirically based motor control model shows that both neural and anatomical components contribute to USV production, which suggests that changes in strain specific USVs or USV changes in disease models can result from both altered motor programs and laryngeal geometry. Our work provides a quantitative neuromechanical framework to evaluate the contributions of brain and body in shaping USVs and a first step in linking descending motor control to USV production.

3.
J Ethnopharmacol ; 282: 114583, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-34487850

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Herb-derived anti-tumor agents, such as paclitaxel and vincristine, exert significant but varied effectivenesses towards different cancer types. Similarly, Centipeda minima (CM) is a well-known traditional Chinese medicine that has been used to treat rhinitis, relieve pain and reduce swelling, and recently found to exert overwhelming anti-tumor effects against breast cancer, colon cancer, and nasopharyngeal carcinoma with different response rates. However, what is the optimizing cancer model that benefits most from CM, and what is the specific target underlying still require more exclusive and profound investigations. AIMS OF THE STUDY: This study aimed to explore the dominant tumor model and specific target of CM by integrative pharmacology and biological experiments. MATERIALS AND METHODS: The most predominant and specific cancer types that are sensitive to CM were screened and identified based on a combination network pharmacology and bioinformatics analysis. Compound-target network and protein-protein interaction of CM-related cancer targets were carried out to determine the most abundant active compound. Simultaneously, the priority target responsible for CM-related anti-tumor efficacy was further validated by molecular docking and in vitro experiments. RESULTS: In total, approximately 42% (8/19) of the targets were enriched in prostate cancer (p = 1.25E-09), suggesting prostate cancer would be the most sensitive tumor response to CM-related efficacy. Furthermore, we found that arnicolide D (ARD), the most abundant and representative active compound of CM, could directly bind to Src with binding energy of -7.3 kcal/mol, implying Src would be the priority target responsible for CM-related anti-tumor efficacy. Meanwhile, the results were further validated by solvent-induced protein precipitation (SIP) assay. In addition, PCR and WB results also revealed that either CM or ARD could not influence the gene expression of Src, while significantly decreased its protein expression instead, which further suggested that ARD might markedly shortene the Src protein half-life to promote Src protein degradation, thereby achieving significant anti-prostate cancer efficacy. CONCLUSION: Our findings not only suggest CM as a promising Src-targeting candidate for prostate cancer treatment, but also bring up a strategy for understanding the personalization of herbal medicines by using integrative pharmacology.

4.
Environ Toxicol ; 2021 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-34873829

RESUMO

The critical roles of E3 ubiquitin ligase RNF168 have been widely revealed in various tumors, however, its roles in lung cancer progression are still confusing. Here, we found that RNF168 expression is positively correlated with the overall survival, first-progression survival, and postprogression survival of lung adenocarcinoma, but not correlated with these survivals of squamous cell carcinoma of lung. Furthermore, it was shown that RNF168 mRNA expression is lowly expressed in lung adenocarcinoma tissues, but highly expressed in squamous cell carcinoma of lung. Functional experiments indicated that RNF168 overexpression significantly suppressed the cancer stem cell (CSC)-like traits of nonsmall cell lung cancer (NSCLC) cells, as characterized by the attenuation of sphere-formation ability, ALDH activity, and the expression of lung CSC markers. Mechanistic studies demonstrated that RNF168 facilitated the ubiquitination of RhoC, which had been considered as a fascinating target for CSCs, and thus promoted RhoC protein degradation. Notably, RNF168 failed to affect the mRNA expression of RhoC and overexpression of RhoC rescued the inhibitory effects of RNF168 overexpression on the CSC-like traits of NSCLC cells. Therefore, this study revealed RNF168 as a novel regulator of RhoC protein in NSCLC cells, this RNF168/RhoC regulatory axis might be a potential target for NSCLC treatment.

5.
Annu Int Conf IEEE Eng Med Biol Soc ; 2021: 6187-6191, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34892529

RESUMO

The motion ability of patients in the acute phase of stroke is difficult to define with existing indexes such as the Brunnstrom stage. Hence, for designing a novel evaluation index for stroke rehabilitation in the acute phase, we focused on the differences between the skin deformations in active and passive movements. Skin deformation reflects the activities of body tissues that are related to motion ability. We measured skin deformations on the upper arm in active and passive movements during elbow flexion and extension and extracted features from these deformations. For practical rehabilitation applications, we developed a novel flexible distance sensor array to reduce the time needed for attaching sensors to patients. Using principal component analysis (PCA), the skin deformation could be decomposed into joint movements and activeness of movements as the first two components (PC1 and PC2). The joint angle and PC1 exhibited a high correlation, and the standard deviation (SD) of PC2 indicated a significant difference in the types of movements. From the above results, we concluded that the SD ratio between PC2 and PC1 may be used to evaluate motion ability considering the inherent biomechanical characteristics.

6.
Environ Int ; 159: 107024, 2021 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-34894487

RESUMO

BACKGROUND: Intake of conventionally grown fruits and vegetables (FVs) is an important route of exposure to pesticide residues in the general population. However, whether health risk stemming from exposure to pesticides through diet could offset benefits of consuming FVs is unclear. OBJECTIVE: We assessed the association of FV intake, classified according to their pesticide residue status, with total and cause-specific mortality. METHODS: We followed 137,378 women (NHS, 1998-2019, and NHSII, 1999-2019) and 23,502 men (HPFS, 1998-2020) without cardiovascular disease, cancer, or diabetes at baseline. FV intake was assessed using validated food frequency questionnaires and categorized as having high- or low-pesticide-residues using data from the USDA Pesticide Data Program. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI) for total and cause-specific mortality associated with high- and low-pesticide-residue FV intake. RESULTS: A total of 27,026 deaths, including 4,318 from CVD and 6,426 from cancer, were documented during 3,081,360 person-years of follow-up. In multivariable-adjusted analyses, participants who consumed ≥4 servings/day of low-pesticide-residue FVs had 36% (95% CI: 32%-41%) lower mortality risk compared to participants who consumed <1 serving/day. The corresponding estimate for high-pesticide residue FV intake was 0.93 (95% CI: 0.81-1.07). This pattern was similar across the three most frequent causes of death (cardiovascular disease, cancer and respiratory diseases). CONCLUSIONS: High-pesticide-residue FV intake was unrelated whereas low-pesticide residue FV intake was inversely related to all-cause mortality, suggesting that exposure to pesticide residues through diet may offset the beneficial effect of FV intake on mortality.

7.
Am J Clin Nutr ; 2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34864844

RESUMO

BACKGROUND: Vitamin D may have a role in immune responses to viral infections. However, data on the association between vitamin D and SARS-CoV-2 infection and Coronavirus Disease 2019 (COVID-19) severity have been limited and inconsistent. OBJECTIVE: We examined the associations of predicted vitamin D status and intake with risk of SARS-CoV-2 infection and COVID-19 severity. DESIGN: We used data from periodic surveys (May 2020 to March 2021) within the Nurses' Health Study II. Among 39,315 participants, 1,768 reported a positive test for SARS-CoV-2 infection. Usual vitamin D intake from foods and supplements were measured using a semi-quantitative, pre-pandemic food frequency questionnaire in 2015. Predicted 25-hydroxyvitamin D [25(OH)D] levels were calculated based on a previously validated model including dietary and supplementary vitamin D intake, ultraviolet-B (UVB), and other behavioral predictors of vitamin D status. RESULTS: Higher predicted 25(OH)D levels, but not vitamin D intake, were associated with a lower risk of SARS-CoV-2 infection. Comparing participants in the highest quintile of predicted 25(OH)D levels to the lowest, the multivariable-adjusted odds ratio was 0.76 (95% CI: 0.58, 0.99; P-trend = 0.04). Participants in the highest quartile of UVB (OR: 0.76; 95% CI: 0.66, 0.87; P-trend = 0.002) and UVA (OR: 0.76; 95% CI: 0.66, 0.88; P-trend<0.001) also had lower risk of SARS-CoV-2 infection compared to the lowest. High intake of vitamin D from supplements (≥400 IU/d) was associated with a lower risk of hospitalization (OR: 0.51; 95% CI: 0.29, 0.91; P-trend = 0.04). CONCLUSIONS: Our study provides suggestive evidence on the association between higher predicted circulating 25(OH)D levels and a lower risk of SARS-CoV-2 infection. Greater intake of vitamin D supplements was associated with a lower risk of hospitalization. Our data also support an association between exposure to UVB or UVA, independent of vitamin D, and SARS-CoV-2 infection, so results for predicted 25(OH)D need to be interpreted cautiously.

8.
BMC Pulm Med ; 21(1): 423, 2021 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-34930196

RESUMO

BACKGROUND: Endobronchial ultrasound (EBUS) elastography has been used in EBUS-guided transbronchial needle aspiration (EBUS-TBNA) to identify malignant lymph nodes based on tissue stiffness. Rapid onsite cytological evaluation (ROSE) has been widely utilized for onsite evaluation of sample adequacy and for guiding sampling during EBUS-TBNA. The aim of this study was to investigate the diagnostic value of combined EBUS elastography and ROSE in evaluating mediastinal and hilar lymph node status. METHODS: Retrospective chart review was performed from December 2018 to September 2020. Patient demographics, EBUS elastography scores, and ROSE, pathologic, and clinical outcome data were collected. The EBUS elastography scores were classified as follows: Type 1, predominantly nonblue; Type 2, partially blue and partially nonblue; and Type 3, predominantly blue. A receiver operating characteristic curve was used to compare the sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio for evaluation of malignant lymph nodes among the EBUS elastography, ROSE, and EBUS combined with ROSE groups. RESULTS: A total of 245 patients (345 lymph nodes) were included. The sensitivity and specificity of the EBUS elastography group for the diagnosis of malignant lymph nodes were 90.51% and 57.26%, respectively. The sensitivity and specificity in the ROSE group were 96.32% and 79.05%, respectively. The sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of EBUS elastography combined with ROSE were 86.61%, 92.65%, 11.78, and 0.14, respectively, and the area under the curve was 0.942. CONCLUSIONS: Combining EBUS elastography and ROSE significantly increased the diagnostic value of EBUS-TBNA in evaluating mediastinal and hilar lymph node status compared to each method alone.

9.
PLoS One ; 16(12): e0260600, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34971557

RESUMO

OBJECTIVE: To explore the feasibility of using random forest (RF) machine learning algorithm in assessing normal and malignant peripheral pulmonary nodules based on in vivo endobronchial optical coherence tomography (EB-OCT). METHODS: A total of 31 patients with pulmonary nodules were admitted to Department of Respiratory Medicine, Zhongda Hospital, Southeast University, and underwent chest CT, EB-OCT and biopsy. Attenuation coefficient and up to 56 different image features were extracted from A-line and B-scan of 1703 EB-OCT images. Attenuation coefficient and 29 image features with significant p-values were used to analyze the differences between normal and malignant samples. A RF classifier was trained using 70% images as training set, while 30% images were included in the testing set. The accuracy of the automated classification was validated by clinically proven pathological results. RESULTS: Attenuation coefficient and 29 image features were found to present different properties with significant p-values between normal and malignant EB-OCT images. The RF algorithm successfully classified the malignant pulmonary nodules with sensitivity, specificity, and accuracy of 90.41%, 77.87% and 83.51% respectively. CONCLUSION: It is clinically practical to distinguish the nature of pulmonary nodules by integrating EB-OCT imaging with automated machine learning algorithm. Diagnosis of malignant pulmonary nodules by analyzing quantitative features from EB-OCT images could be a potentially powerful way for early detection of lung cancer.


Assuntos
Algoritmos , Aprendizado de Máquina , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Tomografia de Coerência Óptica , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Inflamação/patologia , Masculino , Pessoa de Meia-Idade , Curva ROC , Tomografia Computadorizada por Raios X
10.
Clin Epigenetics ; 13(1): 220, 2021 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-34906185

RESUMO

BACKGROUND: Early lung cancer detection remains a clinical challenge for standard diagnostic biopsies due to insufficient tumor morphological evidence. As epigenetic alterations precede morphological changes, expression alterations of certain imprinted genes could serve as actionable diagnostic biomarkers for malignant lung lesions. RESULTS: Using the previously established quantitative chromogenic imprinted gene in situ hybridization (QCIGISH) method, elevated aberrant allelic expression of imprinted genes GNAS, GRB10, SNRPN and HM13 was observed in lung cancers over benign lesions and normal controls, which were pathologically confirmed among histologically stained normal, paracancerous and malignant tissue sections. Based on the differential imprinting signatures, a diagnostic grading model was built on 246 formalin-fixed and paraffin-embedded (FFPE) surgically resected lung tissue specimens, tested against 30 lung cytology and small biopsy specimens, and blindly validated in an independent cohort of 155 patients. The QCIGISH diagnostic model demonstrated 99.1% sensitivity (95% CI 97.5-100.0%) and 92.1% specificity (95% CI 83.5-100.0%) in the blinded validation set. Of particular importance, QCIGISH achieved 97.1% sensitivity (95% CI 91.6-100.0%) for carcinoma in situ to stage IB cancers with 100% sensitivity and 91.7% specificity (95% CI 76.0-100.0%) noted for pulmonary nodules with diameters ≤ 2 cm. CONCLUSIONS: Our findings demonstrated the diagnostic value of epigenetic imprinting alterations as highly accurate translational biomarkers for a more definitive diagnosis of suspicious lung lesions.

11.
Oxid Med Cell Longev ; 2021: 7617839, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34745423

RESUMO

Background: Oxidative stress has a vital role in the early stages of vitiligo. Autoantigens released from apoptotic melanocytes (MC) under oxidative stress are involved in the presentation and recognition of antigens. However, the transport of autoantigens to the cell surface and their release to the extracellular environment are still unclear. Apoptotic bodies (ABs) have always been considered as a key source of immunomodulators and autoantigens. Yet, the role of ABs in the immune mechanism of vitiligo is still unknown. Purpose: To explore whether MC's autoantigens translocate into ABs during oxidative stress-induced apoptosis and study the molecular mechanisms underlying autoantigen migration and AB formation. Methods: PIG3V (an immortalized human vitiligo melanocyte cell line) were treated with H2O2, and ABs were separated. Transmission electron microscopy, flow cytometry, Western blot, mass spectrometry, and other methods were used to determine the relocation of specific antigens in PIG3V cells to ABs. After pretreatment with specific inhibitors (Rho kinase (Y-27632), myosin light chain kinase (MLCK, ML-9), pan-caspase (zVAD-FMK), and JNK (SP600125)), the pathway of autoantigen translocation into ABs and the formation of apoptotic bodies were determined. Results: When treated with 0.8 mM H2O2, ABs were released from these cells. Autoantigens such as tyrosinase-related protein 1 (TYRP-1) and cleavage nuclear membrane antigen Lamin A/C (Asp230) were concentrated in ABs. The expression of autoantigens and the formation of ABs increased in a time- and dose-dependent manner after treatment with H2O2, while the application of specific inhibitors inhibited the formation of apoptotic bodies, i.e., the expression of antigens. Conclusion: Vitiligo autoantigens translocate into ABs in the process of apoptosis induced by oxidative stress. The cytoskeletal protein activation pathway and the JNK-related apoptosis pathway are involved in the transport of autoantigens and the formation of ABs. ABs may be the key bridge between MC cell apoptosis and cellular immunity.

12.
J Biomed Mater Res A ; 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34792851

RESUMO

The need for a substitute for allograft and autograft is rising as bone graft surgeries exceed available supplies. We investigated the efficacy of the low-molecular weight marine bioactive compound fucoidan (FUC) on bone regeneration and implant fixation in seven female sheep, as FUC has shown great promise as a bone substitute. Titanium implants were inserted bilaterally in the distal femurs to test three hydroxyapatite/fucoidan (HA/FUC) groups and compared to allograft. The HA was coated with either 500 or 1500 µg of FUC, obtained by microwave-assisted chemical extraction, or 500 µg of FUC obtained by an enzyme-assisted extraction method. The concentric 2-mm gap around the implant was filled with either one of the HA/FUCs or allograft from the donor sheep. After 12 weeks, implant-bone blocks were harvested and divided into three parts for mechanical push-out testing, immunohistochemistry, and micro-CT and histomorphometry. Pronounced bone formations were observed by micro-CT and histomorphometry in all groups, but higher bone volume fractions were seen in the allograft group compared to the three HA/FUC groups. The trabecular thickness, trabecular separation, and architectural anisotropy were all significantly higher in the allograft group compared to the three HA/FUC groups. In conclusion, adequate bone formation was observed in all groups, although the bone formation was significantly greater in the allograft group. Also, no significant differences existed in the shear mechanical properties between groups, suggesting that the combination of HA and FUC can achieve a similar fixation strength to allograft in this model.

13.
IEEE Access ; 9: 95730-95753, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34812398

RESUMO

The beginning of 2020 has seen the emergence of coronavirus outbreak caused by a novel virus called SARS-CoV-2. The sudden explosion and uncontrolled worldwide spread of COVID-19 show the limitations of existing healthcare systems in timely handling public health emergencies. In such contexts, innovative technologies such as blockchain and Artificial Intelligence (AI) have emerged as promising solutions for fighting coronavirus epidemic. In particular, blockchain can combat pandemics by enabling early detection of outbreaks, ensuring the ordering of medical data, and ensuring reliable medical supply chain during the outbreak tracing. Moreover, AI provides intelligent solutions for identifying symptoms caused by coronavirus for treatments and supporting drug manufacturing. Therefore, we present an extensive survey on the use of blockchain and AI for combating COVID-19 epidemics. First, we introduce a new conceptual architecture which integrates blockchain and AI for fighting COVID-19. Then, we survey the latest research efforts on the use of blockchain and AI for fighting COVID-19 in various applications. The newly emerging projects and use cases enabled by these technologies to deal with coronavirus pandemic are also presented. A case study is also provided using federated AI for COVID-19 detection. Finally, we point out challenges and future directions that motivate more research efforts to deal with future coronavirus-like epidemics.

14.
J Clin Ultrasound ; 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34751454

RESUMO

The absence of left atrial appendage (LAA) is relatively rare, especially with type A Wolff-Parkinson-White syndrome. Secondly, we diagnosed it by multimodal imaging including two-dimensional (2D) and three-dimensional (3D) transesophageal echocardiography (TEE), CT, electrophysiological examination, and 3D electro anatomical mapping system, which is more comprehensive.

15.
Hepatology ; 2021 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-34735734

RESUMO

BACKGROUND & AIMS: Hepatic ischemia reperfusion (HIR) injury, a common clinical complication of liver transplantation and resection, affects patient prognosis. RNF5 is an E3 ubiquitin ligase that plays important roles in endoplasmic reticulum stress, unfolded protein reactions, and inflammatory responses; however, its role in HIR is unclear. APPROACH & RESULTS: RNF5 expression was significantly downregulated during HIR in mice and hepatocytes. Subsequently, RNF5 knockdown and overexpression cell lines were subjected to hypoxia-reoxygenation challenge. The results shown that RNF5 knockdown significantly increased hepatocyte inflammation and apoptosis, while RNF5 overexpression had the opposite effect. Furthermore, hepatocyte-specific RNF5 knockout and transgenic mice were established and subjected to HIR, and RNF5 deficiency markedly aggravated liver damage, cell apoptosis, and activated hepatic inflammatory responses. While hepatic RNF5 transgenic mice had the opposite effect compared with RNF5 knockout mice. Mechanistically, RNF5 interacted with PGAM5 and mediated the degradation of PGAM5 through K48-linked ubiquitination, thereby inhibiting the activation of ASK1 and its downstream JNK/p38. This eventually suppresses the inflammatory response and cell apoptosis in HIR. CONCLUSION: We revealed that RNF5 protected against HIR via its interaction with PGAM5 to inhibit the activation of ASK1 and the downstream JNK/p38 signaling cascade. Our findings indicate that the RNF5-PGAM5 axis may be a promising therapeutic target for HIR.

16.
Plant Physiol Biochem ; 168: 10-16, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34607207

RESUMO

Increase of crop yield is always the desired goal, manipulation of genes in relation to plant growth is a shortcut to promote crop yield. The plasma membrane (PM) H+-ATPase is the plant master enzyme; the energy yielded by ATP hydrolysis pumps H+ out of cells, establishes the membrane potential, maintains pH homeostasis and provides the proton-motive force required for transmembrane transport of many materials. PM H+-ATPase is involved in root nutrient uptake, epidermal stomatal opening, phloem sucrose loading and unloading, and hypocotyl cell elongation. In this review, we summarize the recent progresses in roles of PM H+-ATPase in nutrient uptake and light-induced stomatal opening and discuss the pivotal role of PM H+-ATPase in crop yield improvement and its potential application in agricultural production by modulating the expression of PM H+-ATPase in crops.

17.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(5): 1606-1609, 2021 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-34627448

RESUMO

OBJECTIVE: To investigate the expression and clinical significance of serum protein ROCK2 in patients with chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: The patients were divided into cGVHD group and control group (without cGVHD). The expression levels of serum protein ROCK2 were detected by ELISA in patients with or without cGVHD after allo-HSCT. RESULTS: The expression level of ROCK2 in serum of cGVHD patients was significantly higher than those in control group, moreover, the expression level of ROCK2 in severe cGVHD group was significant higher than that in moderate and mild cGVHD group (P<0.001). The expression level of ROCK2 was significantly decreased in the serum of cGVHD patients after treatment(P<0.01); the expression level of ROCK2 was significantly higher in the serum of cGVHD patients with lung as the target organ(P<0.01). The median survival time of patients with severe cGVHD were significantly shorter than that of patients with mild and moderate cGVHD(P<0.05). CONCLUSION: ROCK2 shows certain reference value in the evaluation of severity and prognosis of cGVHD, and may be a new target for the treatment of cGVHD.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Proteínas Sanguíneas , Doença Crônica , Humanos , Transplante Homólogo , Quinases Associadas a rho
18.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(5): 1645-1648, 2021 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-34627454

RESUMO

OBJECTIVE: To analyze the clinical characteristics of patients with POEMS syndrome and explore its effective treatment strategies. METHODS: The clinical data of 75 patients with POEMS syndrome treated in The First Affiliated Hospital of Zhengzhou University from June 2012 to June 2018 were collected and retrospectively analyzed. The clinical characteristics, treatment regimes and outcomes of the patients were summarized. RESULTS: The median age of 75 diagnosed patients was 50 (30-81) years old and 100% (75/75) of the patients were accompanied with peripheral neuropathy, 77.3% (58/75) with organ enlargement, 82.7% (62/75) with endocrine abnormality, 93.3% (70/75) with monoclonal plasma cell diseases and 64.0% (48/75) with skin changes. Among the 75 patients, 5 cases gave up treatment, while the others showed varying degrees of improvement after treatment. The hematological complete remission (CRH) rate of the 70 patients was 28.6% and the rate of neurological remission (RN) was 85.7%. BD and RD regimens showed better efficacy in CRH and RN than old schemes, such as VAD and COP (P<0.05). Two patients underwent sequential autologous hematopoietic stem cell transplantation (HSCT) after BD chemotherapy and achieved ideal therapeutic effects, including the significant improvement of peripheral neurological symptoms and the M protein turned negative. The median follow-up time of the 70 patients was 42 (4-103) months, while the 2-year overall survival rate (OS) was 86.7%, and the 5-year OS was 81.0%. CONCLUSION: The clinical manifestations of POEMS syndrome are complex and diverse, the clinicians therefore should be vigilant to reduce the misdiagnosis and missed diagnosis. Bortezomib or Lenalidomide can be recommended as the first-line medicines and autologous HSCT should be considered for appropriate patients.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Síndrome POEMS , Idoso , Idoso de 80 Anos ou mais , Humanos , Lenalidomida , Pessoa de Meia-Idade , Síndrome POEMS/terapia , Estudos Retrospectivos , Transplante Autólogo
19.
Eur J Med Chem ; 226: 113889, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34649182

RESUMO

GSK3 is a promising target for the treatment of Alzheimer's disease. Here, we describe the design and synthesize of a series of GSK3 degraders based on a click chemistry platform. A series of highly potent GSK3 degraders were obtained. Among them, PT-65 exhibited most potent degradation potency against GSK3α (DC50 = 28.3 nM) and GSK3ß (DC50 = 34.2 nM) in SH-SY5Y cells. SPR assay confirmed that PT-65 binds to GSK3ß with high affinity (KD = 12.41 nM). The proteomic study indicated that PT-65 could selectively induced GSK3 degradation. Moreover, PT-65 could effectively suppress GSK3ß and Aß mediated tau hyperphosphorylation in a dose-dependent manner and protect SH-SY5Y cells from Aß caused cell damage. We also confirmed that PT-65 could suppress OA induced tau hyperphosphorylation and ameliorate learning and memory impairments in vivo model of AD. In summary, PT-65 might be a promising candidate for the treatment of AD.

20.
IMA Fungus ; 12(1): 31, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34670626

RESUMO

In this study, the complete mitochondrial genome of O. gracilis was sequenced and assembled before being compared with related species. As the second largest mitogenome reported in the family Ophiocordycipitaceae, the mitogenome of O. gracilis (voucher OG201301) is a circular DNA molecule of 134,288 bp that contains numerous introns and longer intergenomic regions. UCA was detected as anticodon in tRNA-Sec of O. gracilis, while comparative mitogenome analysis of nine Ophiocordycipitaceae fungi indicated that the order and contents of PCGs and rRNA genes were considerably conserved and could descend from a common ancestor in Ophiocordycipitaceae. In addition, the expansion of mitochondrial organization, introns, gene length, and order of O. gracilis were determined to be similar to those of O. sinensis, which indicated common mechanisms underlying adaptive evolution in O. gracilis and O. sinensis. Based on the mitochondrial gene dataset (15 PCGs and 2 RNA genes), a close genetic relationship between O. gracilis and O. sinensis was revealed through phylogenetic analysis. This study is the first to investigate the molecular evolution, phylogenetic pattern, and genetic structure characteristics of mitogenome in O. gracilis. Based on the obtained results, the mitogenome of O. gracilis can increase understanding of the genetic diversity and evolution of cordycipitoid fungi.

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