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1.
Insect Sci ; 31(1): 236-254, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37370252

RESUMO

In a tritrophic context of plant-insect-entomopathogen, plants play important roles in modulating the interaction of insects and their pathogenic viruses. Currently, the influence of plants on the transmission of insect viruses has been mainly studied on baculoviruses and some RNA viruses, whereas the impact of plants on other insect viruses is largely unknown. Here, we identified a new densovirus infecting the green peach aphid Myzus persicae and tested whether and how host plants influence the transmission of the aphid densovirus. The complete single-stranded DNA genome of the virus, M. persicae densovirus 2, is 5 727 nt and contains inverted terminal repeats. Transcription and phylogenetic analysis indicated that the virus was distinct from other a few identified aphid densoviruses. The virus abundance was detected highly in the intestinal tract of aphids, compared with the lower level of it in other tissues including head, embryo, and epidermis. Cabbage and pepper plants had no obvious effect on the vertical transmission and saliva-mediated horizontal transmission of the virus. However, the honeydew-mediated horizontal transmission among aphids highly depended on host plants (65% on cabbages versus 17% on peppers). Although the virus concentration in the honeydew produced by aphids between 2 plants was similar, the honeydew production of the infected aphids reared on peppers was dramatically reduced. Taken together, our results provide evidence that plants influence the horizontal transmission of a new densovirus in an aphid population by modulating honeydew secretion of aphids, suggesting plants may manipulate the spread of an aphid-pathogenic densovirus in nature.


Assuntos
Afídeos , Densovirus , Animais , Afídeos/genética , Filogenia
2.
J Phys Chem Lett ; 14(45): 10113-10118, 2023 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-37921693

RESUMO

The effects of CaCl2 and MgCl2 on the cloud point temperature of two different elastin-like polypeptides (ELPs) were studied using a combination of cloud point measurements, molecular dynamics simulations, and infrared spectroscopy. Changes in the cloud point for the ELPs in aqueous divalent metal cation solutions were primarily governed by two competing interactions: the cation-amide oxygen electrostatic interaction and the hydration of the cation. In particular, Ca2+ cations can more readily shed their hydration shells and directly contact two amide oxygens by the formation of ion bridges. By contrast, Mg2+ cations were more strongly hydrated and preferred to partition toward the amide oxygens along with their hydration shells. In fact, although hydrophilic ELP V5A2G3 was salted-out at low concentrations of MgCl2, it was salted-in at higher salt concentrations. By contrast, CaCl2 salted the ELP sharply out of solution at higher salt concentrations because of the bridging effect.


Assuntos
Elastina , Peptídeos , Elastina/química , Cloreto de Cálcio , Peptídeos/química , Amidas/química , Cátions/química , Cátions Bivalentes
3.
J Exp Zool A Ecol Integr Physiol ; 339(10): 978-993, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37602652

RESUMO

Ammonia is a common environmental stress factor that constrains aquaculture industry development. This study evaluated the effect of carbohydrate levels and ammonia stress in oriental river prawn (Macrobrachium nipponense). The experiment had six treatments containing two water ammonia levels (0 and 5 mg/L) and three dietary carbohydrate levels (low carbohydrate diet (LCD, 10%), medium carbohydrate diet [MCD, 20%], and high carbohydrate diet [HCD, 30%]), and lasted six weeks. The results showed that the prawns fed on MCD had higher weight gain than those fed on LCD and HCD during ammonia stress. Moreover, the prawns fed on MCD had significantly lower acid phosphatase and alkaline phosphatase activities during ammonia stress. Feeding the prawns on the MCD increased B cells in the hepatopancreas during ammonia stress. Interestingly, the prawns fed on MCD had significantly lower superoxide dismutase activity compared to LCD and HCD during ammonia stress. Moreover, the prawns fed on MCD had significantly lower pyruvate kinase activity and pyruvate and lactic acid contents, while those fed on LCD had significantly higher succinic dehydrogenase, 6-phosphogluconic dehydrogenase, and phosphoenol pyruvate carboxykinase activities during ammonia stress. The prawns fed on the MCD increased significantly glutaminase activity and decreased the ammonia content in the serum during ammonia exposure. In addition, feeding the prawns on MCD decreased significantly the expression of apoptosis and inflammation-related genes. Taken together, the MCD supplied energy required to counteract ammonia stress, which increased growth, improved antioxidant capacity, facilitated ammonia excretion, and alleviated inflammation and apoptosis of the oriental river prawn.


Assuntos
Antioxidantes , Palaemonidae , Animais , Antioxidantes/metabolismo , Palaemonidae/genética , Palaemonidae/metabolismo , Amônia/metabolismo , Amônia/farmacologia , Carboidratos da Dieta/metabolismo , Carboidratos da Dieta/farmacologia , Inflamação , Piruvatos/metabolismo , Piruvatos/farmacologia , Glucose/metabolismo , Glucose/farmacologia
4.
Phytomedicine ; 118: 154957, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37478683

RESUMO

BACKGROUND: Hyperuricemia is an important pathological basis of gout and a distinct hazard factor for metabolic syndromes and cardiovascular and chronic renal disease, but lacks safe and effective treatments currently. Paeonia × suffruticosa Andrews leaf effectively reduced serum uric acid in gout patients; however, the material foundation and the mechanism remain unclear. PURPOSE: To determine the primary active components and mechanism of P. suffruticosa leaf in hyperuricemic mice. METHODS: The chemical constituents of P. suffruticosa leaf was identified using high-performance liquid chromatographic analysis. The anti-hyperuricemic activity of P. suffruticosa leaf extract (12.5, 25, 50, 100, and 200 mg/kg) and its components was evaluated in hyperuricemic mice induced by a high purine diet for 14 days. Then, the urate-lowering effects of apigenin 7-O-glucoside (0.09, 0.18, and 0.36 mg/kg) were assessed in another hyperuricemic mice model built by administrating potassium oxonate and adenine for 4 weeks. The inhibitory effect of apigenin 7-O-glucoside on uric acid production was elucidated by investigating xanthine oxidase activity in vitro and in serum and the liver and through molecular docking. Immunofluorescence and western blot analyses of the expression of renal urate transporter 1 (URAT1), glucose transporter 9 (GLUT9), organic anion transporters 1 (OAT1), and ATP-binding cassette G member 2 (ABCG2) proteins elucidated how apigenin 7-O-glucoside promoted uric acid excretion. RESULTS: Six compounds were identified in P. suffruticosa leaf: gallic acid, methyl gallate, oxypaeoniflorin, paeoniflorin, galloylpaeoniflorin, and apigenin 7-O-glucoside. P. suffruticosa leaf extract significantly attenuated increased serum uric acid, creatinine, and xanthine oxidase activity in hyperuricemic mice. Apigenin 7-O-glucoside from P. suffruticosa leaf reduced uric acid, creatinine, and malondialdehyde serum levels, increased superoxide dismutase activity, and partially restored the spleen coefficient in hyperuricemic mice. Apigenin 7-O-glucoside inhibited xanthine oxidase activity in vitro and decreased serum and liver xanthine oxidase activity and liver xanthine oxidase protein expression in hyperuricemic mice. Molecular docking revealed that apigenin 7-O-glucoside bound to xanthine oxidase. Apigenin 7-O-glucoside facilitated uric acid excretion by modulating the renal urate transporters URAT1, GLUT9, OAT1, and ABCG2. Apigenin 7-O-glucoside protected against renal damage and oxidative stress caused by hyperuricemia by reducing serum creatinine, blood urea nitrogen, malondialdehyde, and renal reactive oxygen species levels; increasing serum and renal superoxide dismutase activity; restoring the renal coefficient; and reducing renal pathological injury. CONCLUSION: Apigenin 7-O-glucoside is the main urate-lowering active component of P. suffruticosa leaf extract in the hyperuricemic mice. It suppressed liver xanthine oxidase activity to decrease uric acid synthesis and modulated renal urate transporters to stimulate uric acid excretion, alleviating kidney damage caused by hyperuricemia.


Assuntos
Gota , Hiperuricemia , Transportadores de Ânions Orgânicos , Paeonia , Camundongos , Animais , Hiperuricemia/tratamento farmacológico , Hiperuricemia/induzido quimicamente , Ácido Úrico , Xantina Oxidase/metabolismo , Creatinina , Simulação de Acoplamento Molecular , Apigenina/farmacologia , Rim , Transportadores de Ânions Orgânicos/metabolismo , Superóxido Dismutase/metabolismo , Glucosídeos/farmacologia , Malondialdeído/metabolismo , Ácido Oxônico/efeitos adversos
5.
ACS Macro Lett ; 12(7): 841-847, 2023 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-37318585

RESUMO

We propose a mechanism for α-helix folding of polyalanine in aqueous urea that reconciles experimental and simulation studies. Over 15 µs long, all-atom simulations reveal that, upon dehydrating the protein's first solvation shell, a delicate balance between localized urea-residue dipole interactions and hydrogen bonds dictates polypeptide solvation properties and structure. Our work clarifies the experimentally observed tendency of these alanine-rich systems to form secondary structures at low and intermediate urea concentrations. Moreover, it is consistent with the commonly accepted hydrogen-bond-induced helix unfolding, dominant at high urea concentrations. These results establish a structure-property relationship highlighting the importance of microscopic dipole-dipole orientations/interactions for the operational understanding of macroscopic protein solvation.

6.
Clin Respir J ; 17(7): 647-653, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37315930

RESUMO

INTRODUCTION: The metastases of lung cancer to bilateral choroids symmetrically and simultaneously are very rare. Almost all patients with choroid metastasis can be treated with external beam radiotherapy in order to increase quality of life and preserve vision. MATERIAL AND METHODS: We documented a case and studied the effect of icotinib on choroidal metastases in bilateral eyes simultaneously from pulmonary adenocarcinoma. RESULTS: A 49-year-old Chinese man presented with bilateral vision losing simultaneously for 4 weeks, it was as an initial presentation in the clinical. The examinations with ophthalmofundoscopy, ultrasonography, and fluorescein angiography showed the lesions in bilateral choroids, two solitary juxtapapillary yellow-white choroidal metastases inferior to the optic discs with bleeding. Positron emission tomography confirmed the choroidal metastases and further proved that it was from lung cancer with lymph nodes and multiple bone metastasis. The biopsy taken from the lung by bronchoscopy and needle biopsy from supraclavicular lymph nodes revealed the pulmonary adenocarcinoma with epithelial growth factor receptor mutation (exon 21). The patient was treated with oral icotinib (125 mg, three times a day, TID). Five days after starting icotinib therapy, the patient's visions were rapidly recovered. Two months after the treatment with icotinib, the choroidal metastases regressed to small lesions, and the visions were preserved to before. The lung tumor and other metastatic lesions were partly regressive. There was no evidence of recurrence for eye lesions at 15-months follow-up. After 17 months treating by icotinib, the patient presented headache and dizzy with multiple brain metastases determined by magnetic resonance imaging; however, the lesions of the choroidal metastases remained progressing-free. Almonertinib with radiotherapy were used to treat the brain metastases, and he is surviving with progress-free more than 2 years until now. CONCLUSION: Bilateral choroidal metastases from lung cancer symmetrically are very rare. Icotinib following by almonertinib was an alternative therapy for choroidal metastasis from non-small cell lung cancer with epithelial growth factor receptor mutation.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Encefálicas , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Masculino , Humanos , Pessoa de Meia-Idade , Neoplasias Pulmonares/patologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Qualidade de Vida , Adenocarcinoma de Pulmão/tratamento farmacológico , Corioide/patologia , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundário
7.
ACS Macro Lett ; 12(2): 234-240, 2023 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-36706453

RESUMO

We investigate the effect of helicity in isolated polymers on the topological chirality of their knots with computer simulations. Polymers are described by generic worm-like chains (WLC), where helical conformations are promoted by chiral coupling between segments that are neighbors along the chain contour. The sign and magnitude of the coupling coefficient u determine the sense and strength of helicity. The corrugation of the helix is adjusted via the radius R of a spherical, hard excluded volume around each WLC segment. Open and compact helices are, respectively, obtained for R that is either zero or smaller than the length of the WLC bond, and R that is a few times larger than the bond length. We use a Monte Carlo algorithm to sample polymer conformations for different values of u, spanning the range from achiral polymers to chains with well-developed helices. Monitoring the average helix torsion and fluctuations of chiral order as a function of u, for two very different chain lengths, demonstrates that the coil-helix transition in this model is not a phase transition but a crossover. Statistical analysis of conformations forming the simplest chiral knots, 31, 51, and 52, demonstrates that topological mirror symmetry is broken─knots formed by helices with a given sense prefer one handedness over the other. For the 31 and 51 knots, positive helical sense favors positive handedness. Intriguingly, an opposite trend is observed for 52 knots, where positive helical sense promotes negative handedness. We argue that this special coupling between helicity and topological chirality stems from a generic mechanism: conformations where some of the knot crossings are found in "braids" formed by two tightly interwoven sections of the polymer.

8.
High Alt Med Biol ; 23(3): 264-272, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35723652

RESUMO

Ma, Xuexinyu, Yang Pan, Yuye Xue, Yao Li, Yan Zhang, Yani Zhao, Xingzhao Xiong, Jianbo Wang, and Zhifu Yang. Tetrahydrocurcumin ameliorates acute hypobaric hypoxia-induced cognitive impairment in mice. High Alt Med Biol. 23:264-272, 2022. Background: Hypobaric hypoxia (HH) impairs spatial learning and increases oxidative stress in rodents. We hypothesized that tetrahydrocurcumin (THC) may attenuate HH-induced neurobehavioral deficits by reducing HH-induced lipid peroxidation and increasing glycolytic activity. Materials and Methods: A C57BL/6 mouse model of acute high altitude brain injury was established using an animal decompression chamber for 24 hours. Cognitive and behavioral assessments were conducted using the Y-maze, open field, and Rotarod tests. We measured superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity; malondialdehyde (MDA) and reactive oxygen species levels; anti-neuronal core antigen (NeuN) immunoreactivity; and active occludin, hypoxia-inducible factor-1α, glucose transporter 1 (GLUT1), and GLUT3 expression levels in mice brain tissue. Results: The mice in the THC group showed improved cognitive impairment compared with those in the HH group in cognitive and behavioral tests, but failed to show improvement in the decline in coordination. The mice in the THC group were more effected than those in the HH group in demonstrating alleviation of hyperemia in cortical vessels and cell voids, and cells in the CA1 region were more closely arranged. Compared with those in the mice of the HH group, the concentration of MDA decreased significantly, the expression of occludin, NeuN immunoreactivity, and the activities of SOD and GSH-Px significantly increased in the mice of the THC group. An increase in GLUT1 expression was observed in HH-exposed animals (N group vs. HH group: 0.4 ± 0.08 vs. 0.60 ± 0.07, p < 0.05), and this increase was enhanced in animals treated with THC (HH group vs. THC group: 0.60 ± 0.07 vs. 0.82 ± 0.08, p < 0.05). Conclusions: THC improved cognitive impairment in mice, accompanied by reduced oxidative stress and increased GLUT1 protein levels.


Assuntos
Disfunção Cognitiva , Curcumina , Animais , Camundongos , Antioxidantes/metabolismo , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/etiologia , Curcumina/análogos & derivados , Transportador de Glucose Tipo 1/metabolismo , Hipóxia/complicações , Hipóxia/tratamento farmacológico , Hipóxia/metabolismo , Camundongos Endogâmicos C57BL , Ocludina/metabolismo , Estresse Oxidativo , Superóxido Dismutase/metabolismo
9.
Phys Chem Chem Phys ; 24(17): 10346-10355, 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35438114

RESUMO

The combined effect of a weakly hydrated and a strongly hydrated anion on the lower critical solution temperature (LCST) of poly(N-isopropylacrylamide)(PNIPAM) is nonadditive (Bruce et al., J. Am. Chem. Soc., 2019, 141, 6609). Herein, we revisit the molecular origin of this effect by performing atomistic molecular dynamics simulations of a 40mer PNIPAM chain in solutions with a fixed concentration of Na2SO4 and an increasing concentration of NaI. Our results show that the nonadditive ion effects on the coil-to-globule transitions of PNIPAM arise due to the interplay between the depletion of the strongly hydrated sulfate ions and the preferential accumulation of the iodide ions on the polymer surface leading to favourable PNIPAM-I- interactions. The depletion of the sulfate ions and the binding of the iodide ions are coupled through the role of the cation leading to a mutual enhancement of both effects. This mutual enhancement effect correlates with the partitioning of the Na+ cations from the counterion cloud of the weakly hydrated iodide ions to the counterion cloud of the strongly hydrated sulfate ions and the corresponding changes in water affinity of the ions.

10.
Nucleic Acids Res ; 50(8): 4355-4371, 2022 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-35390161

RESUMO

A key role of chromatin kinases is to phosphorylate histone tails during mitosis to spatiotemporally regulate cell division. Vaccinia-related kinase 1 (VRK1) is a serine-threonine kinase that phosphorylates histone H3 threonine 3 (H3T3) along with other chromatin-based targets. While structural studies have defined how several classes of histone-modifying enzymes bind to and function on nucleosomes, the mechanism of chromatin engagement by kinases is largely unclear. Here, we paired cryo-electron microscopy with biochemical and cellular assays to demonstrate that VRK1 interacts with both linker DNA and the nucleosome acidic patch to phosphorylate H3T3. Acidic patch binding by VRK1 is mediated by an arginine-rich flexible C-terminal tail. Homozygous missense and nonsense mutations of this acidic patch recognition motif in VRK1 are causative in rare adult-onset distal spinal muscular atrophy. We show that these VRK1 mutations interfere with nucleosome acidic patch binding, leading to mislocalization of VRK1 during mitosis, thus providing a potential new molecular mechanism for pathogenesis.


Assuntos
Histonas , Nucleossomos , Cromatina/genética , Microscopia Crioeletrônica , DNA/genética , DNA/metabolismo , Histonas/genética , Histonas/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular , Fosforilação , Proteínas Serina-Treonina Quinases , Treonina/metabolismo
11.
Macromol Rapid Commun ; 43(12): e2100907, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35124875

RESUMO

Elastin-like polypeptides (ELPs) are well-known proline-rich stimulus-responsive polymers. They have broad applications ranging from drug delivery to green chemistry. Recently, the authors have shown that the cis/trans proline isomerization can be used to regulate their conformational behavior while keeping the lower critical solution temperature (LCST) unchanged in pure water. In aqueous ethanol mixtures, ELPs typically exhibit an expanded-collapsed-expanded transition known as the co-non-solvency phenomenon. Since it is unclear how proline isomerization affects the solvation behavior of ELPs in aqueous ethanol mixtures, an all-atom insight on single ELPs has been provided to address this question. It is found that if all proline residues are in the cis state, the peptides only experience a collapsed-expanded transition as ethanol concentration increases, i.e., the initial collapse vanishes because cis isomers prefer the compact structures in pure water. The data from the authors also suggest that proline isomerization does not change the shift in solvation free energy of an ELP with given sequence, but it varies the affinity of the peptide to both the solvent and cosolvent molecules.


Assuntos
Elastina , Prolina , Elastina/química , Etanol , Isomerismo , Peptídeos/química , Solventes/química , Temperatura , Água/química
12.
J Pain Res ; 14: 3711-3721, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34899000

RESUMO

Complex regional pain syndrome (CRPS) is a chronic pain disorder characterized by spontaneous or evoked regionally-confined pain which is out of proportion to the initial trauma event. The disease can seriously affect the quality of the patients' life, increase the psychological burden, and cause various degrees of disability. Despite the awareness of CRPS among medical practitioners for over a century, its pathogenesis remains unclear, and the available treatment is still unsatisfactory. Effective animal models are the foundation of disease research, which is helpful in understanding the pathogenesis and an in-depth exploration of the appropriate therapeutic approaches. Currently, researchers have established a series of animal models of the disease. There are four main CRPSI animal models: chronic post-ischemic pain (CPIP) model, tibial fracture/cast immobilization model, passive transfer-trauma model, and the needlestick-nerve-injury (NNI) model. The modeling methods of these models are constantly improving over time. In preclinical studies, the interpretation of experimental results and the horizontal comparison between similar studies may be affected by the nature of the experimental animal breeds, sex, diet, and psychology. There is need to facilitate the choice of appropriate animal models and avoid the interference of the factors influencing animal models on the interpretation of research results. The review will provide a basic overview of the influencing factors, modeling methods, and the characteristics of CRPSI animal models.

13.
PLoS One ; 16(9): e0255504, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34473729

RESUMO

Benzophenone (BPs) and 4-Methylbenzylidene Camphor are used as ultraviolet (UV) filters to protect the skin and hair in personal care products. The discharging of the three chemicals may endanger the receiving water ecosystem. In the present study, the mutagenicity of BP-6, BP-8, and 4-Methylbenzylidene Camphor was tested using the Salmonella typhimurium reverse mutation test (Ames test) in the system with and without rat liver microsomal preparations (S9). Four S.typhimurium strains, TA97, TA98, TA100, and TA102 were employed in the Ames tests. The mutagenicity was detected from all three chemicals. The addition of S9 increased the mutation ratios of three chemicals to four strains, except BP-6 to TA100 strain and 4-MBC to TA97 and TA98 strain. In the mixed experiment, all positive effects were detected in the absence of S9. However, the results all became negative in the presence of S9. For the mixture of BP-6 and 4-MBC, positive results were detected on four tester strains except for the TA100 strain. For the mixture of BP-6, BP-8, and 4-MBC, positive results were detected on four strains. The mixture test results showed antagonism in mutagenicity for the mixture of BP-6 and 4-MBC to TA98 and TA100 strains and the mixture of BP-6, BP-8, and 4-MBC to TA100 and TA102 strains.


Assuntos
Benzofenonas/toxicidade , Cânfora/análogos & derivados , Mutagênese/efeitos dos fármacos , Testes de Mutagenicidade/métodos , Salmonella typhimurium/efeitos dos fármacos , Protetores Solares/toxicidade , Raios Ultravioleta/efeitos adversos , Animais , Bioensaio , Cânfora/toxicidade , Monitoramento Ambiental/métodos , Humanos , Microssomos Hepáticos/efeitos dos fármacos , Ratos , Salmonella typhimurium/genética
14.
J Phys Chem B ; 125(34): 9751-9756, 2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34424695

RESUMO

Responsiveness of polypeptides and polymers in aqueous solution plays an important role in biomedical applications and in designing advanced functional materials. Elastin-like polypeptides (ELPs) are a well-known class of synthetic intrinsically disordered proteins (IDPs), which exhibit a lower critical solution temperature (LCST) in pure water and in aqueous solutions. Here, we compare the influence of cis/trans proline isomerization on the phase behavior of single ELPs in pure water. Our results reveal that proline isomerization tunes the conformational behavior of ELPs while keeping the transition temperature unchanged. We find that the presence of the cis isomers facilitates compact structures by preventing peptide-water hydrogen bonding while promoting intramolecular interactions. In other words, the LCST transition of ELPs with all proline residues in the cis state occurs with almost no noticeable conformational change.


Assuntos
Elastina , Água , Isomerismo , Peptídeos , Prolina
15.
Cancer Cell Int ; 21(1): 424, 2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34376212

RESUMO

BACKGROUND: Glioma is a common primary central nervous system tumour, and therapeutic drugs that can effectively improve the survival rate of patients in the clinic are lacking. Bufalin is effective in treating various tumours, but the mechanism by which it promotes the apoptosis of glioma cells is unclear. The aim of this study was to investigate the drug targets of bufalin in glioma cells and to clarify the apoptotic mechanism. METHODS: Cell viability and proliferation were evaluated by CCK-8 and colony formation assays. Then, the cell cycle and apoptosis, intracellular ion homeostasis, oxidative stress levels and mitochondrial damage were assessed after bufalin treatment. DARTS-PAGE technology was employed and LC-MS/MS was performed to explore the drug targets of bufalin in U251 cells. Molecular docking and western blotting were performed to identify potential targets. siRNA targeting Annexin A2 and the DRP1 protein inhibitor Mdivi-1 were used to confirm the targets of bufalin. RESULTS: Bufalin upregulated the expression of cytochrome C, cleaved caspase 3, p-Chk1 and p-p53 proteins to induce U251 cell apoptosis and cycle arrest in the S phase. Bufalin also induced oxidative stress in U251 cells, destroyed intracellular ion homeostasis, and caused mitochondrial damage. The expression of mitochondrial division-/fusion-related proteins in U251 cells was abnormal, the Annexin A2 and DRP1 proteins were translocated from the cytoplasm to mitochondria, and the MFN2 protein was released from mitochondria into the cytoplasm after bufalin treatment, disrupting the mitochondrial division/fusion balance in U251 cells. CONCLUSIONS: Our research indicated that bufalin can cause Annexin A2 and DRP1 oligomerization on the surface of mitochondria and disrupt the mitochondrial division/fusion balance to induce U251 cell apoptosis.

16.
Eur J Pharmacol ; 908: 174334, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34265299

RESUMO

Benign prostatic hyperplasia (BPH) is a frequently encountered disease in older men that affects sexual function and is capable of causing lower urinary tract dysfunction. Unfortunately, current treatment options for BPH primarily seek to address the lower urinary tract dysfunction aspect of the disease and do not improve sexual function. Yohimbine has been effectively used for decades to treat erectile dysfunction. Therefore, the objective of this study was to evaluate the inhibitory effect of yohimbine on BPH and explore the associated underlying mechanisms. Thirty-six rats were randomly divided into the control, BPH, finasteride (1 mg/kg), and yohimbine (2, 4, and 8 mg/kg) groups. Except for the rats in the control group, those in the other groups were subcutaneously injected testosterone propionate (5 mg/kg/day) daily for a period of 4 weeks to establish BPH models. They were also administration the corresponding drug daily for a period of 6 weeks. After the treatments, in addition to determining prostate wet weight and index, the histopathological status of the prostate was observed, and the levels of testosterone, dihydrotestosterone, prostatic acid phosphatase, the prostate-specific antigen, proliferating cell nuclear antigen, and steroid 5α-reductase were determined. Specifically, the administration of 2, 4, and 8 mg/kg yohimbine inhibited prostatic index increase by 46.7, 55.1, and 69.3%, respectively, in BHP rats. Further, yohimbine significantly reduced the levels of dihydrotestosterone, prostatic acid phosphatase, prostate-specific antigen, proliferating cell nuclear antigen, and steroid 5α-reductase, suggesting that it exerts beneficial effects against BPH by modulating the steroid 5α-reductase pathway.


Assuntos
Hiperplasia Prostática , 3-Oxo-5-alfa-Esteroide 4-Desidrogenase , Animais , Di-Hidrotestosterona , Finasterida , Masculino , Ratos , Ioimbina
17.
Am J Clin Exp Urol ; 9(3): 221-228, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34327261

RESUMO

INTRODUCTION: To explore the efficacy of urine cytology, ureteroscopic biopsy, and a combination of both in detecting HG UTUC. METHODS: We searched our institutional pathology database for cases (2008-2018) with urine cytology and subsequent histologic follow-up based on ureteroscopic biopsy and extirpative resection performed within 6 months of the urine cytology. Sensitivity, specificity, positive predictive value and negative predictive value were calculated for the specific diagnostic categories. RESULTS: A cohort of 226 cases with both urine cytology and histologic follow-up based on ureteroscopic biopsies and/or surgical resection were included in the study. 144/226 cases (64%) had both urine cytology and extirpative resection, among which 57 (25%) cases also have ureteroscopic biopsy preoperatively. The sensitivities for urine cytology or ureteroscopic biopsy alone for a surgically confirmed HG UTUC were 64.7% and 59.2% respectively. Among 49 cases diagnosed as HG-UTUC by extirpative resection, 42 cases were diagnosed as HG-UTUC by either urine or biopsy diagnosis. The sensitivity of combining urine cytology and ureteroscopic biopsy was 85.7%, which was significantly higher than either method alone (P < 0.05). CONCLUSION: Our findings show urine cytology and ureteroscopic biopsy have comparable sensitivity in diagnosing HG UTUC. However, by combining urine cytology with ureteroscopic biopsy, there is a significant increase in the sensitivity for detecting HG UTUC and should therefore be incorporated into routine clinical practice.

18.
Biomed Res Int ; 2021: 6624245, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33997029

RESUMO

The aim of this study was to develop and validate a nomogram model to predict the risk of decreased activities of daily living (ADLs) in patients with moyamoya disease (MMD) following revascularization. The nomogram model was constructed based on data from 292 patients with MMD that were treated at Qilu Hospital of Shandong University from January 2018 to June 2019. The prediction model was assessed using a dataset of 119 patients with MMD collected from July 2019 to June 2020. Patients were evaluated with a general information questionnaire and the Mini Mental Status Examination, Hospital Anxiety and Depression Scale, Social Support Rating Scale, and ADL Scale. Multivariable logistic regression analysis was applied to build a prediction model incorporating the features selected in the least absolute shrinkage and selection operator regression model. Discrimination, calibration, and clinical usefulness of the prediction model were assessed using receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis. Predictors contained in the nomogram included gender, age, monthly income, hypertension, and cognitive function and depression scores. The areas under the ROC curves of the training and testing datasets were 0.938 and 0.853, respectively. The prediction model displayed good calibration, and the decision curve analysis showed that it had a wide range of clinical applications. This novel predictive could be conveniently used to predict the risk of the decreased living activity ability in patients with MMD.


Assuntos
Atividades Cotidianas , Doença de Moyamoya/patologia , Revascularização Miocárdica , Nomogramas , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Curva ROC
19.
Bull Environ Contam Toxicol ; 105(6): 874-881, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33231746

RESUMO

Most of the pollutants discharged into the water will deposit at the bottom of the river and may cause biological toxicity. Daphnia magna-elutriate toxicity bioassay was usually applied to evaluate sediment toxicity. However, the loss of hydrophobic pollutants during the elutriating will lead to the underestimation of sediment toxicity. The purpose of this study is to apply the optimized immobilized sediments to D. magna test, so it can be directly exposed to the sediments and get accurate sediment toxicity results. The optimized immobilized sediment was prepared by mixing 1 g sediment with 7.5 mL 3% (w/v) alginate and hardened in a 4% (w/v) CaCl2 solution. Based on D. magna acute toxicity test, the median lethal concentration values (LC50) of the spiked Cu and diuron measured by using immobilized sediment were both lower than that of using the elutriate, in which the difference of Cu-LC50 reached a significant level. The toxicity changes of sediment in the polluted rivers before and after dredging were then be evaluated by using the immobilized sediment. The toxicity of the sediments at four sites decreased from acute-toxic (pro-dredging) to slight-acute-toxic and nontoxic (post-dredging).


Assuntos
Sedimentos Geológicos/química , Poluentes Químicos da Água/toxicidade , Animais , Bioensaio , Daphnia , Diurona , Poluentes Ambientais , Poluição Ambiental , Dose Letal Mediana , Rios/química , Testes de Toxicidade Aguda , Água , Poluentes Químicos da Água/análise
20.
Phytother Res ; 34(11): 2963-2977, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32573860

RESUMO

High-altitude cerebral oedema (HACE) is a potentially fatal manifestation of high-altitude sickness and is caused partly by inflammation and the blood-brain barrier disruption. Tetrahydrocurcumin (THC) has been reported to exert effective antioxidative and anti-inflammatory effects; This study sought to elucidate the underlying mechanism of THC in mitigating HACE using a mouse model. Our results revealed that prophylactic administration of THC (40 mg/kg) for 3 days significantly alleviated the increase in brain water content (BWC), interleukin-1ß (IL-1ß) and TNF-α levels caused by acute hypobaric hypoxia (AHH). Additionally, superoxide dismutase (SOD) activity was increased by THC to enhance the ability to resist hypoxia. Histological and ultrastructural analysis of the cerebrum revealed that THC administration mitigated AHH-induced pericellular oedema and reduced the perivascular space, resulting in the simultaneous remission of oedema and protection of mitochondria in the cerebrum. In vitro, astrocytes exposed to hypoxia (4% O2 ) for 24 hr exhibited and increase in IL-1ß expression followed by an increase in vascular endothelial growth factor (VEGF) levels. Furthermore, THC administration remarkably downregulated VEGF, matrix metallopeptidase-9 (MMP-9), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) expression, both in vivo and in vitro. Our data highlight the potential prophylactic activity of THC in HACE, it effectively mitigates AHH-induced cerebral oedema and inflammation is associated with the inhibition of the NF-κB/ VEGF/MMP-9 pathways.


Assuntos
Doença da Altitude/tratamento farmacológico , Edema Encefálico/tratamento farmacológico , Hipóxia Celular/efeitos dos fármacos , Curcumina/análogos & derivados , Inflamação/tratamento farmacológico , NF-kappa B/metabolismo , Animais , Curcumina/farmacologia , Curcumina/uso terapêutico , Modelos Animais de Doenças , Humanos , Masculino , Camundongos , Fator A de Crescimento do Endotélio Vascular/metabolismo
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