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1.
Cardiovasc Diabetol ; 23(1): 116, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38566123

RESUMO

BACKGROUND: Diabetic cardiomyopathy (DCM) is a serious complication in patients with type 1 diabetes mellitus (T1DM), which still lacks adequate therapy. Irisin, a cleavage peptide off fibronectin type III domain-containing 5, has been shown to preserve cardiac function in cardiac ischemia-reperfusion injury. Whether or not irisin plays a cardioprotective role in DCM is not known. METHODS AND RESULTS: T1DM was induced by multiple low-dose intraperitoneal injections of streptozotocin (STZ). Our current study showed that irisin expression/level was lower in the heart and serum of mice with STZ-induced TIDM. Irisin supplementation by intraperitoneal injection improved the impaired cardiac function in mice with DCM, which was ascribed to the inhibition of ferroptosis, because the increased ferroptosis, associated with increased cardiac malondialdehyde (MDA), decreased reduced glutathione (GSH) and protein expressions of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4), was ameliorated by irisin. In the presence of erastin, a ferroptosis inducer, the irisin-mediated protective effects were blocked. Mechanistically, irisin treatment increased Sirtuin 1 (SIRT1) and decreased p53 K382 acetylation, which decreased p53 protein expression by increasing its degradation, consequently upregulated SLC7A11 and GPX4 expressions. Thus, irisin-mediated reduction in p53 decreases ferroptosis and protects cardiomyocytes against injury due to high glucose. CONCLUSION: This study demonstrated that irisin could improve cardiac function by suppressing ferroptosis in T1DM via the SIRT1-p53-SLC7A11/GPX4 pathway. Irisin may be a therapeutic approach in the management of T1DM-induced cardiomyopathy.


Assuntos
Diabetes Mellitus Tipo 1 , Cardiomiopatias Diabéticas , Ferroptose , Humanos , Animais , Camundongos , Cardiomiopatias Diabéticas/tratamento farmacológico , Cardiomiopatias Diabéticas/etiologia , Cardiomiopatias Diabéticas/prevenção & controle , Sirtuína 1 , Fibronectinas , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/tratamento farmacológico , Proteína Supressora de Tumor p53 , Miócitos Cardíacos
2.
Arch Virol ; 169(4): 74, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38480558

RESUMO

Triple motif protein 21 (TRIM21) has an antiviral function that inhibits various viral infections. However, its role in the progress of influenza A virus (IAV) infection is unclear. In this study, we investigated the role and molecular mechanism of TRIM21 in IAV infection. RT-qPCR was used to determine the level of TRIM21 mRNA, and ELISA was used to measure the levels of IFN-α, IFN-ß, IL-6, and TNF-α. The levels of the TRIM21, NP, TBK1, IRF3, p-TBK1, and p-IRF3 proteins were estimated by Western blot. The results showed that, after IAV infection, TRIM21 was upregulated in clinical patient serum and A549 cells, and this was correlated with the IFN response. Overexpression of TRIM21 reduced IAV replication and transcription in in vitro cell experiments. TRIM21 also increased IFN-α and IFN-ß levels and decreased IL-6 and TNF-α levels in A549 cells. In addition, overexpression of TRIM21 inhibited IAV-induced apoptosis. Further experiments demonstrated that TBK1-IRF3 signaling was activated by TRIM21 and was involved in the inhibitory effect of TRIM21 on virus replication. In summary, our study suggests that TRIM21 inhibits viral replication by activating the TBK1-IRF3 signaling pathway, further inhibiting the infection process of IAV.


Assuntos
Vírus da Influenza A Subtipo H1N1 , Vírus da Influenza A , Influenza Humana , Humanos , Células A549 , Inflamação , Vírus da Influenza A/metabolismo , Vírus da Influenza A Subtipo H1N1/metabolismo , Influenza Humana/genética , Fator Regulador 3 de Interferon/genética , Fator Regulador 3 de Interferon/metabolismo , Interferon-alfa/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais/fisiologia , Fator de Necrose Tumoral alfa/metabolismo
3.
Dalton Trans ; 53(5): 2193-2206, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38193212

RESUMO

Due to the antitumor properties, Zn(II) complexes have attracted more and more attention. Herein, three novel tetranuclear Zn(II) complexes 1-3 based on dihydrazone pyrimidine derivatives H2L1-H2L3 were synthesized and characterized using IR spectroscopy, 1H NMR spectroscopy, single crystal X-ray diffraction analysis, XRD, TG and elemental analysis. Single crystal X-ray diffraction analysis revealed that 1-3 all displayed a [2 × 2] grid-like topology. The stability in solution, lipophilicity, confocal imaging and antitumor activities were investigated. Complexes 1-3 displayed high structural stability, membrane permeability and different lipophilicities. They can target mitochondria due to the cation charge. The MTT assay indicated that all of them exhibited stronger antiproliferative activity than the corresponding derivatives H2L1-H2L3 and the well-known cisplatin against all the selected tumor cells (BGC-823, BEL-7402, MCF-7 and A549), with IC50 values ranging from 2.83 µM to 7.97 µM. AO/EB double staining, flow cytometry and ROS detection suggested that complexes 1 and 2 could induce BGC-823 apoptosis in a dose-dependent manner. UV-Vis spectra, CD spectra, viscosity analysis and molecular docking revealed that complexes 1 and 2 interact with DNA mainly via partial intercalation and groove binding. Tetranuclear [2 × 2] grid-like Zn(II) complexes have the potential to be promising antitumor agents in the future.


Assuntos
Antineoplásicos , Complexos de Coordenação , Simulação de Acoplamento Molecular , Antineoplásicos/química , Cisplatino/farmacologia , Pirimidinas/farmacologia , Zinco/química , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química , Linhagem Celular Tumoral , Proliferação de Células
4.
Cancer Nurs ; 47(2): 141-150, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-36728137

RESUMO

BACKGROUND: Esophageal cancer patients suffer from multiple and severe symptoms during the postoperative recovery period. Family caregivers play a vital role in assisting patients to cope with their symptoms. OBJECTIVE: To examine the concordance of esophageal cancer patients and their caregivers on assessing patients' symptoms after surgery and identify predictors associated with the symptom concordance. METHODS: In this cross-sectional study, 213 patient-caregiver dyads completed general information questionnaires, the Memorial Symptom Assessment Scale, the Depression Subscale of Hospital Anxiety and Depression Scale, the Mutuality Scale, and the Zarit Burden Interview (for caregivers). Data were analyzed using intraclass correlation coefficients, paired t tests, and binary logistic regression. RESULTS: At the dyad level, agreement of patients' and caregivers' reported symptoms ranged from poor to fair. At the group level, patients reported significantly higher scores than caregivers in most symptoms. Of the 213 dyads, 119 (55.9%) were identified as concordant on symptom assessment. Patients' nasogastric tube, perceived mutuality, caregivers' educational background, and dyad's communication frequency with each other could predict their concordance of symptom assessment. CONCLUSIONS: There were relatively low agreements between esophageal cancer patients and caregivers on assessing patients' symptoms, and caregivers tended to underestimate patients' symptoms. The dyad's symptom concordance was influenced by patient-, caregiver-, and dyad-related factors. IMPLICATIONS FOR PRACTICE: Having an awareness of the incongruence on assessing symptoms between esophageal cancer patients and caregivers may help healthcare professionals to comprehensively interpret patients' symptoms and develop targeted dyadic interventions to improve their concordance, contributing to optimal symptom management and health outcomes.


Assuntos
Cuidadores , Neoplasias Esofágicas , Humanos , Estudos Transversais , Esofagectomia/efeitos adversos , Avaliação de Sintomas , Neoplasias Esofágicas/cirurgia , Qualidade de Vida
5.
Phytother Res ; 38(1): 174-186, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37849425

RESUMO

Psoriasis is a common immune-mediated inflammatory skin disease, caused by disturbed interactions between keratinocytes and immune cells. Chinese medicine shows potential clinical application for its treatment. Liquiritin is a flavone compound extracted from licorice and shows potential antitussive, antioxidant and antiinflammatory effects, and therefore may have potential as a psoriasis therapeutic. The aim of this work was to examine the possible roles that liquiritin may have in treating psoriasis. HaCaT cells were stimulated by TNF-α with or without liquiritin, harvested for analysis by western blots and RT-qPCR, and the cellular supernatants were collected and analyzed by ELISA for cytokines. In addition, 4 groups of mice were examined: Normal, Vehicle, LQ-L and LQ-H. The mice were sacrificed after 6 days and analyzed using IHC, ELISA, RT-qPCR and flow cytometry. The results showed that liquiritin could significantly inhibit the progression of psoriasis both in vitro and in vivo. Liquiritin strongly suppressed the proliferation of HaCaT keratinocytes but did not affect cell viability. Moreover, liquiritin alleviated imiquimod-induced psoriasis-like skin inflammation and accumulation of Th17 cells and DCs in vivo. In TNF-α-induced HaCaT keratinocytes, both protein and mRNA expression levels of inflammatory cytokines were sharply decreased. In imiquimod-induced mice, the activation of NF-κB and AP-1 was reduced after treatment with liquiritin. Collectively, our results show that liquiritin might act as a pivotal regulator of psoriasis via modulating NF-κB and AP-1 signal pathways.


Assuntos
Flavanonas , Glucosídeos , NF-kappa B , Psoríase , Camundongos , Animais , NF-kappa B/metabolismo , Fator de Transcrição AP-1/metabolismo , Imiquimode/uso terapêutico , Fator de Necrose Tumoral alfa/metabolismo , Células Th17 , Linhagem Celular , Psoríase/induzido quimicamente , Psoríase/tratamento farmacológico , Queratinócitos , Citocinas/metabolismo , Proliferação de Células , Camundongos Endogâmicos BALB C , Modelos Animais de Doenças
6.
SSM Popul Health ; 24: 101497, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37674978

RESUMO

Background: This study explored the association of marital transitions and frailty among Chinese middle-aged and older people and whether this association differs by social support. Methods: We used a sample of 12,388 adults aged ≥45 years who participated in the China Health and Retirement Longitudinal Study (CHARLS) between 2015 and 2018. Between-wave changes in marital status ("married at both times", "unmarried to married", "married to unmarried", "unmarried at both times") were used to explore the changes in frailty measured by the frailty index (FI), which was constructed from 55 health variables. Social support was evaluated based on social engagement and intergenerational support. The associations among marital transitions, social support and frailty were analyzed using generalized estimating equations (GEEs). Results: The mean FI of 12,388 participants was 0.23 (SD = 0.13). Participants who were married to unmarried (ß = 0.014, B = 0.005, P = 0.012) and unmarried at both times (ß = 0.022, B = 0.003, P < 0.001) had significant a positive impact on FI compared with participants who were married at both times. Social engagement, financial support by children and providing care to grandchildren had an interactive effect with marital transitions in influencing FI. Conclusions: Being unmarried may increase frailty among Chinese middle-aged and older adults. Financial support by children may mitigate the adverse effects of being unmarried on frailty.

7.
Cell Mol Life Sci ; 80(5): 128, 2023 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-37084140

RESUMO

Outcomes following human dense connective tissue (DCT) repair are often variable and suboptimal, resulting in compromised function and development of chronic painful degenerative diseases. Moreover, biomarkers and mechanisms that guide good clinical outcomes after DCT injuries are mostly unknown. Here, we characterize the proteomic landscape of DCT repair following human Achilles tendon rupture and its association with long-term patient-reported outcomes. Moreover, the potential regulatory mechanisms of relevant biomarkers were assessed partly by gene silencing experiments. A mass-spectrometry based proteomic approach quantified a large number (769) of proteins, including 51 differentially expressed proteins among 20 good versus 20 poor outcome patients. A novel biomarker, elongation factor-2 (eEF2) was identified as being strongly prognostic of the 1-year clinical outcome. Further bioinformatic and experimental investigation revealed that eEF2 positively regulated autophagy, cell proliferation and migration, as well as reduced cell death and apoptosis, leading to improved DCT repair and outcomes. Findings of eEF2 as novel prognostic biomarker could pave the way for new targeted treatments to improve healing outcomes after DCT injuries.Trial registration: NCT02318472 registered 17 December 2014 and NCT01317160 registered 17 March 2011, with URL http://clinicaltrials.gov/ct2/show/NCT02318472 and http://clinicaltrials.gov/ct2/show/study/NCT01317160 .


Assuntos
Tendão do Calcâneo , Tecido Conjuntivo , Fator 2 de Elongação de Peptídeos , Humanos , Tendão do Calcâneo/lesões , Tendão do Calcâneo/metabolismo , Apoptose , Autofagia/genética , Biomarcadores , Morte Celular , Tecido Conjuntivo/metabolismo , Proteômica
8.
Int Arch Allergy Immunol ; 184(5): 447-459, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36657406

RESUMO

INTRODUCTION: Influenza A virus (IAV) infection causes severe lung inflammation and injury, particularly in children. Sirtuin3 (Sirt3) was confirmed to be effective in protecting the lung against injury. This study aims to explore the function and mechanism of Sirt3 on influenza development in children. METHODS: The Sirt3 level in serum samples from IAV-infected children and lung epithelial cells were detected using RT-qPCR, ELISA, and Western blot assays. Cell viability and apoptosis were determined by MTT and flow cytometry assays. Virus titration was conducted by determining TCID50. Cell inflammatory response was detected by a battery of inflammatory cytokines. The contents of ROS and ATP, mitochondrial membrane potential level, and oxygen-consumption rate were examined to reflect on oxidative stress and mitochondrial dysfunction. The activity of poly (ADP-ribose) polymerase 1 (PARP-1) was measured by colorimetry. RESULTS: Sirt3 was downregulated in IAV-infected children's serum samples and BEAS-2B cells. Overexpression of Sirt3 alleviated IAV replication and IAV-induced inflammatory injury, oxidative stress, and mitochondrial dysfunction in lung epithelial cells. Moreover, upregulation of Sirt3 deacetylated SOD2 and PARP-1 and inhibited the PARP-1 activity. Notably, the Sirt3 inhibitor (3-TYP) and PARP-1 activity agonist (nicotinamide) reversed the effects of Sirt3 overexpression on IAV replication and IAV-induced injury. CONCLUSION: Overexpression of Sirt3 attenuated IAV-evoked inflammatory injury and mitochondrial oxidative stress through the inhibition of PARP-1 activity in lung epithelial cells.


Assuntos
Vírus da Influenza A , Influenza Humana , Sirtuína 3 , Criança , Humanos , Células Epiteliais/metabolismo , Inflamação/metabolismo , Vírus da Influenza A/metabolismo , Pulmão/metabolismo , Estresse Oxidativo , Sirtuína 3/genética , Sirtuína 3/metabolismo , Sirtuína 3/farmacologia , Influenza Humana/imunologia , Influenza Humana/metabolismo , Poli(ADP-Ribose) Polimerase-1/metabolismo
9.
Gene ; 859: 147219, 2023 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-36702394

RESUMO

Climate oscillation and its synergistic impacts on habitat fragmentation have been identified as threatening the survival of some extant species. However, the mechanisms by which semi-aquatic insects impacted by such events remain poorly understood. Herein, we studied the largest water strider in the world, Gigantometra gigas, to explore the effect of these two factors on its evolutionary history. The sequences of mitogenomic and nrDNA cluster were utilized to reconstruct phylogenetic relationship among G. gigas populations and its demographic history. Mitochondrial genes were separately reconstructed topologies of that populations and detected remarkable differences. We found that G. gigas populations conform to the isolation-by-distance model, and decline occurred at about 120 ka, which was probably influenced by the climate change during the late Pleistocene and eventually maintained a small effective population size (Ne) around 85,717. The populations in Guangdong Province of China are worthy of note in that they exhibit low genetic diversity, a small Ne around 18,899 individuals, and occupy an area with little suitable future habitat for G. gigas. This work recommends that conservation efforts are implemented to ensure the long-term survival of small G. gigas populations, and notes that further evaluation of their extinction risk under the impacts of human activities is required.


Assuntos
Evolução Biológica , Água , Humanos , Filogenia , China , Variação Genética , DNA Mitocondrial/genética , Ecossistema
10.
J Clin Nurs ; 32(11-12): 2399-2409, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35434874

RESUMO

AIMS AND OBJECTIVES: To compare and rank the effectiveness of non-pharmacological interventions for symptoms of Overactive Bladder (OAB) in network meta-analysis. BACKGROUND: Overactive Bladder affects many patients, which often generates bothersome symptoms and debilitates the quality of life. Non-pharmacological therapies have been widely used in OAB. However, due to insufficient evidence, it remains unclear which strategies are most suitable for OAB. METHODS: We integrated randomised controlled trials (RCTs), which were searched up to 1 January 2021, from 8 databases (PubMed, Embase, Cochrane library, Web of Science, China National Knowledge Infrastructure, Wanfang Database, VIP Database, and China Biology Medicine disc). Studies that met the eligible criteria were assessed the risk of bias. Then, network meta-analyses were conducted by STATA, R, and OpenBUGS. The review followed PRISMA statement. RESULTS: A total of 24 studies comprising 2347 patients with OAB were included in this review, most of which were low to moderate risk of bias. The results of network meta-analysis implied that electric stimulation (ES) was the most effective intervention to reduce voided frequency and nocturia frequency of OAB. CONCLUSIONS: Electric stimulation ranked the best in the management of OAB, and future studies should pay more attention to ES.


Assuntos
Terapia por Estimulação Elétrica , Bexiga Urinária Hiperativa , Feminino , Humanos , Bexiga Urinária Hiperativa/tratamento farmacológico , Metanálise em Rede , Terapia por Estimulação Elétrica/métodos , Viés , China
12.
Nat Commun ; 13(1): 5093, 2022 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-36064840

RESUMO

The hypoxia-inducible factors (HIFs) regulate the main transcriptional pathway of response to hypoxia in T cells and are negatively regulated by von Hippel-Lindau factor (VHL). But the role of HIFs in the regulation of CD4 T cell responses during infection with M. tuberculosis isn't well understood. Here we show that mice lacking VHL in T cells (Vhl cKO) are highly susceptible to infection with M. tuberculosis, which is associated with a low accumulation of mycobacteria-specific T cells in the lungs that display reduced proliferation, altered differentiation and enhanced expression of inhibitory receptors. In contrast, HIF-1 deficiency in T cells is redundant for M. tuberculosis control. Vhl cKO mice also show reduced responses to vaccination. Further, VHL promotes proper MYC-activation, cell-growth responses, DNA synthesis, proliferation and survival of CD4 T cells after TCR activation. The VHL-deficient T cell responses are rescued by the loss of HIF-1α, indicating that the increased susceptibility to M. tuberculosis infection and the impaired responses of Vhl-deficient T cells are HIF-1-dependent.


Assuntos
Subunidade alfa do Fator 1 Induzível por Hipóxia , Tuberculose , Proteína Supressora de Tumor Von Hippel-Lindau , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Hipóxia , Fator 1 Induzível por Hipóxia , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/imunologia , Camundongos , Linfócitos T/imunologia , Tuberculose/genética , Tuberculose/imunologia , Tuberculose/prevenção & controle , Proteína Supressora de Tumor Von Hippel-Lindau/genética , Proteína Supressora de Tumor Von Hippel-Lindau/imunologia
14.
Front Public Health ; 10: 917269, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35875011

RESUMO

Objectives: This study aimed to provide an assessment of chlorothalonil's possible carcinogenic risk posed to the public. In combination and comparison with the non-carcinogenic risk, the results hopefully could provide useful insights, early warning, and references for policy formulation. Methods: This study firstly investigated the occurrence of chlorothalonil on selected key vegetables for different scenarios, and then conducted an exposure assessment with officially published data. Lastly, both the non-carcinogenic and carcinogenic risk of chlorothalonil were calculated by using Monte-Carlo simulation. Results: Even though mean non-carcinogenic risks of chlorothalonil for all scenarios were below threshold value, the mean carcinogenic risks for maximum-risk scenario and most-likely risk scenario were mostly above threshold value. High probabilities of exceedance of threshold value existed for carcinogenic risk under all scenarios. Conclusion: Potential threat to public health existed for conventionally 'safe' pesticide if considering the possible carcinogenicity. Extra caution should be taken and the potential carcinogenic effects should be included into consideration for better protection of public health during the policy formulation process.


Assuntos
Carcinógenos , Verduras , Humanos , Nitrilas , Probabilidade , Medição de Risco
15.
Virus Res ; 319: 198878, 2022 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-35882266

RESUMO

Chinese sacbrood virus (CSBV) poses a serious threat to the apiculture of China. Although several approaches have been attempted to control CSBV infection, their applications have been greatly limited in practical breeding of honeybees due to poor effectiveness. Egg yolk antibodies (EYA) have shown a promising protection for bees against CSBV infection. This study was conducted to produce high titer EYA and then further improve their antiviral effect. Among three vaccination groups, the EYA titer in graphene oxide-chitosan group was highest (1.591 ± 0.145), in Freund's group was modest (1.195 ± 0.040), and in white oil group was lowest (1.058 ± 0.056). After three injections of each vaccine in hens, EYA were produced at the highest level with a 14-day period. After application of EYA for more than two years in actual bee breeding, prevention and treatment assays showed that EYA confered 98.9 to 100% protection from CSBV infection. The mortality of the control group reached to a range of 91.2 to 100%. This study demonstrated that the high titer EYA have been successfully prepared with significant anti-CSBV activity and that these antibodies may feasibly be used for CSBV treatment to meet the practical needs of apiculture.


Assuntos
Antivirais , Vírus de RNA , Animais , Abelhas , Galinhas , Gema de Ovo , Feminino
16.
BMC Palliat Care ; 21(1): 99, 2022 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-35659220

RESUMO

BACKGROUND: Cancer impacts both patients and their family caregivers. This study aimed to explore the interdependence between depression and intimacy in lung cancer patients and their family caregivers, providing the basis for developing a patient-caregiver centered dyadic intervention. METHODS: This cross-sectional study recruited 182 dyads of lung cancer patients and their family caregivers using a convenient sampling. The depression subscale of the Hospital Anxiety and Depression Scale (HADS) and the Mutuality Scale (MS) were used to measure participants' depression and intimacy respectively; and the correlation between depression and intimacy in patients and caregivers was analyzed by establishing the actor-partner interdependence model. RESULTS: Thirty four percent of the patients and 19.2% of the caregivers were at risk of depression, with an intimacy score of 2.67 ± 0.74 points and 2.6 ± 0.86 points, respectively; Pearson correlation analysis showed that there was a positive correlation between the depression score (r = 0.226, P < 0.01) and intimacy score (r = 0.344, P < 0.01) in patients and caregivers; and the results of actor-partner interdependence model showed that caregivers' depression had an actor effect on their own intimacy (b = -0.054, P = 0.004) as well as a partner effect on patients' intimacy (b = -0.041, P = 0.011). However, patients' depression has no influence on the intimacy of patients or caregivers. CONCLUSIONS: There is an interdependent relationship between depression and intimacy in lung cancer patients and family caregivers. Therefore, dyadic interventions can help them to cope with cancer together.


Assuntos
Cuidadores , Neoplasias Pulmonares , Estudos Transversais , Depressão/complicações , Humanos , Neoplasias Pulmonares/complicações , Qualidade de Vida
17.
Nat Metab ; 4(6): 739-758, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35760869

RESUMO

Mitochondria are the main consumers of oxygen within the cell. How mitochondria sense oxygen levels remains unknown. Here we show an oxygen-sensitive regulation of TFAM, an activator of mitochondrial transcription and replication, whose alteration is linked to tumours arising in the von Hippel-Lindau syndrome. TFAM is hydroxylated by EGLN3 and subsequently bound by the von Hippel-Lindau tumour-suppressor protein, which stabilizes TFAM by preventing mitochondrial proteolysis. Cells lacking wild-type VHL or in which EGLN3 is inactivated have reduced mitochondrial mass. Tumorigenic VHL variants leading to different clinical manifestations fail to bind hydroxylated TFAM. In contrast, cells harbouring the Chuvash polycythaemia VHLR200W mutation, involved in hypoxia-sensing disorders without tumour development, are capable of binding hydroxylated TFAM. Accordingly, VHL-related tumours, such as pheochromocytoma and renal cell carcinoma cells, display low mitochondrial content, suggesting that impaired mitochondrial biogenesis is linked to VHL tumorigenesis. Finally, inhibiting proteolysis by targeting LONP1 increases mitochondrial content in VHL-deficient cells and sensitizes therapy-resistant tumours to sorafenib treatment. Our results offer pharmacological avenues to sensitize therapy-resistant VHL tumours by focusing on the mitochondria.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Doença de von Hippel-Lindau , Proteases Dependentes de ATP , Carcinoma de Células Renais/genética , Humanos , Neoplasias Renais/genética , Proteínas Mitocondriais , Biogênese de Organelas , Oxigênio , Doença de von Hippel-Lindau/genética
18.
Health Sociol Rev ; 31(3): 326-341, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35731936

RESUMO

Rates of lung cancer in China are rising rapidly, creating an urgent need for prevention. Effective prevention measures require understanding local beliefs and perceptions about the risk for developing lung cancer. This article explores the explanations that Chinese lung cancer patients and their families give about the aetiology of their disease. Fifty-three interviews were conducted among lung cancer patients and their family members at a large tumour hospital in southern China. Participants presented a complex multifactorial explanation of lung cancer associating their disease with risks like tobacco use, occupational exposures, environmental pollution, lifestyle changes, and personal characters. While these are all standard risk factors commonly associated with lung cancer, participants presented them within a larger contextual frame of structural issues that impede their ability to change their behaviours. Using a social ecological model, we demonstrate how China's socio-cultural environment shapes assumptions about the risk of lung cancer with particular reference to work, home, social situations, and the natural environment.


Assuntos
Neoplasias Pulmonares , Exposição Ocupacional , China/epidemiologia , Meio Ambiente , Humanos , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/etiologia , Exposição Ocupacional/efeitos adversos , Fatores de Risco
19.
Bosn J Basic Med Sci ; 22(4): 635-642, 2022 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-35238287

RESUMO

Thyroid dysfunction and diabetes are reported to be associated with depression. However, their role in the suicide risk in patients with major depressive disorder (MDD) is unclear. The purpose of this study was to investigate and compare thyroid dysfunction and diabetes between suicide attempters and non-suicide attempters in a large sample of first-episode drug-naïve (FEND) MDD patients. A descriptive study was conducted on 1279 Chinese outpatients with a diagnosis of first-episode MDD. Their sociodemographic information, blood levels of thyroid hormones, glucose, lipids and body mass index (BMI) parameters were collected. The positive subscales of the positive and negative syndrome scale (PANSS), Hamilton Anxiety Rating Scale (HAMA), Hamilton Depression Rating Scale (HAMD) were measured for psychotic, anxiety and depressive symptoms. Our results showed that compared with non-suicide attempters (P<0.01), suicide attempters had statistically higher scores on HAMD, HAMA and PANSS psychotic symptoms, as well as higher thyroid stimulating hormone (TSH) serum levels, glucose, anti-thyroglobulin (A-TG), anti-thyroid peroxidase (A-TPO), total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C), systolic blood pressure and diastolic blood pressure (all with P<0.001). These results revealed that TSH, A-TG, A-TPO, TC, TG and LDL-C may be promising biomarkers of suicide risk in MDD, implying the importance of regular assessment of blood glucose level and thyroid function parameters for suicide prevention, along with possible treatment for impaired thyroid function and diabetes for the suicide intervention in MDD patients. Such patients with abnormal blood sugar and TSH must undergo thorough screening for suicidal ideation.


Assuntos
Transtorno Depressivo Maior , Ideação Suicida , Glicemia , LDL-Colesterol , Jejum , Humanos , Índice de Gravidade de Doença , Tireotropina
20.
Aging Clin Exp Res ; 34(6): 1201-1208, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35091970

RESUMO

BACKGROUND: Parkinson's disease (PD) represents the second most common neurodegenerative disease. OBJECTIVE: To evaluate the effects of dance therapy (DT) aimed at improving non-motor symptoms in PD. METHODS: Studies were performed through PubMed, Web of Science, The Cochrane Library, Embase, and Science Direct from inception to October 27, 2021. The data were screened independently by two reviewers, and the quality of the papers was assessed using the Cochrane manual. The included studies were randomized controlled trials and quasi-randomized controlled trials, reporting random-effects standardized mean differences, and 95% confidence intervals as the effect size. I2 statistics were used to assess heterogeneity. The main outcomes included the Montreal Cognitive Assessment Scale (MOCA), Baker Depression Scale (BDI), Parkinson's Fatigue Scale (FPS-16), and Apathy Scale (AS). RevMan 5.3 software was integrated for meta-analysis. RESULTS: Nine literatures were analyzed for the meta-analysis with a total of 307 patients. Random effects showed that DT significantly improved cognitive of PD (MD = 1.50, 95% CI [0.52, 2.48], P = 0.0003; I2 = 51%). However, this meta-analysis demonstrated that dance therapy had no significance for improving depression (MD = - 1.33, 95% CI [- 4.11, 1.45], P = 0.35; I2 = 79%), fatigue (MD = 0.26, 95% CI [- 0.31, 0.83], P = 0.37; I2 = 0%), and apathy (MD = 0.07, 95% CI [- 2.55, 2.69], P = 0.96; I2 = 50%). CONCLUSION: The meta-analysis suggests that dance can improve cognitive function in PD.


Assuntos
Dançaterapia , Doenças Neurodegenerativas , Doença de Parkinson , Cognição , Fadiga/terapia , Humanos
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