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1.
J Mol Neurosci ; 74(1): 30, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38478195

RESUMO

Microglia are resident macrophages within the central nervous system, serving as the first responders to neuroinflammation. Glucocorticoids (GCs) may cause damage to brain tissue, but the specific mechanism remains unclear. This study was divided into two parts: a glucocorticoid receptor (GR) mitochondrial translocation intervention experiment and a mitochondrial oxidative stress inhibition experiment. BV-2 microglia were stimulated with dexamethasone (DEX) and treated with either tubastatin-A or mitoquinone (MitoQ) for 24 h. Our results showed that DEX increased the translocation of GRs to mitochondria, and this effect was accompanied by decreases in the expression of mitochondrially encoded cytochrome c oxidase 1 (MT-CO1) and mitochondrially encoded cytochrome c oxidase 3 (MT-CO3) and increases in the expression of NOD-like receptor thermal protein domain-associated protein 3 (NLRP3), caspase-1, and Gasdermin D (GSDMD). The level of mitochondrial respiratory chain complex IV (MRCC IV) and adenosine triphosphate (ATP) was decreased. An elevation in the level of mitochondrial oxidative stress and the opening of the mitochondrial permeability transition pore (mPTP) was also observed. Mechanistically, tubastatin-A significantly suppressed the mitochondrial translocation of GRs, improved the expression of mitochondrial genes, promoted the restoration of mitochondrial function, and inhibited pyroptosis. MitoQ significantly prevented mitochondrial oxidative stress, improved mitochondrial function, and reduced apoptosis and pyroptosis. Both tubastatin-A and MitoQ suppressed DEX-induced pyroptosis. This study substantiates that the increase in the mitochondrial translocation of GRs mediated by GCs exacerbates oxidative stress and pyroptosis in microglia, which indicates that the regulation of mitochondrial pathways by GCs is pathogenic to microglia.


Assuntos
Glucocorticoides , Piroptose , Glucocorticoides/farmacologia , Glucocorticoides/metabolismo , Receptores de Glucocorticoides/genética , Receptores de Glucocorticoides/metabolismo , Microglia/metabolismo , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Estresse Oxidativo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo
2.
Endocrine ; 84(3): 1238-1249, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38374513

RESUMO

PURPOSE: To determine the relationship between serum total testosterone (TT) levels and oxidative stress indices in patients with polycystic ovary syndrome (PCOS), and to investigate the effect of oxidative stress on androgen synthesis and its mechanism in rat ovarian theca-interstitial (T-I) cells. METHODS: Clinical, hormonal, metabolic, and oxidative stress parameters were analyzed in a cross-sectional case-control study including 626 patients with PCOS and 296 controls. The effects of oxidized low-density lipoprotein (ox-LDL) and oxidized high-density lipoprotein (ox-HDL) on cell proliferation, TT secretion, and expression of key enzymes involved in testosterone synthesis were evaluated in T-I cells. RESULTS: Serum TT levels were elevated with an increase in ox-LDL levels, whereas glutathione concentrations were lower in the high-TT subgroup than in the low-TT subgroup. The average ovarian volume and ox-LDL and malondialdehyde levels were significant predictors of TT levels in the multivariate regression models. In a rat ovarian T-I cell model, lipoprotein and oxidized lipoprotein treatments stimulated proliferation and promoted testosterone secretion. The mRNA and protein levels of 17α-hydroxylase were significantly higher in oxidized lipoprotein-treated cells than those in lipoprotein-treated cells. The mRNA levels of cholesterol side chain cleavage enzyme and steroidogenic acute regulatory protein were also significantly higher in ox-HDL-treated cells than in HDL-treated cells. CONCLUSIONS: Oxidative stress can promote androgen production by up-regulating the expression of testosterone synthesis-related enzymes in vitro and may be an essential factor in elevating serum TT levels in patients with PCOS.


Assuntos
Hiperandrogenismo , Lipoproteínas LDL , Estresse Oxidativo , Síndrome do Ovário Policístico , Testosterona , Síndrome do Ovário Policístico/metabolismo , Feminino , Animais , Ratos , Testosterona/sangue , Lipoproteínas LDL/sangue , Lipoproteínas LDL/metabolismo , Hiperandrogenismo/metabolismo , Adulto , Humanos , Estudos de Casos e Controles , Estudos Transversais , Ovário/metabolismo , Ratos Sprague-Dawley , Adulto Jovem , Células Tecais/metabolismo , Proliferação de Células , Androgênios/sangue , Esteroide 17-alfa-Hidroxilase/metabolismo , Esteroide 17-alfa-Hidroxilase/genética , Células Cultivadas
3.
Lancet Reg Health West Pac ; 45: 101031, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38361774

RESUMO

Background: Recurrence following radical resection in patients with stage IB gastric cancer (GC) is not uncommon. However, whether postoperative adjuvant chemotherapy could reduce the risk of recurrence in stage IB GC remains contentious. Methods: We collected data on 2110 consecutive patients with pathologic stage IB (T1N1M0 or T2N0M0) GC who were admitted to 8 hospitals in China from 2009 to 2018. The survival of patients who received adjuvant chemotherapy was compared with that of postoperative observation patients using propensity score matching (PSM). Two survival prediction models were constructed to estimate the predicted net survival gain attributable to adjuvant chemotherapy. Findings: Of the 2110 patients, 1344 received adjuvant chemotherapy and 766 received postoperative observation. Following the 1-to-1 matching, PSM yielded 637 matched pairs. Among matched pairs, adjuvant chemotherapy was not associated with improved survival compared with postoperative observation (OS: hazard ratio [HR], 0.72; 95% CI, 0.52-1.00; DFS: HR, 0.91; 95% CI, 0.64-1.29). Interestingly, in the subgroup analysis, reduced mortality after adjuvant chemotherapy was observed in the subgroups with elevated serum CA19-9 (HR, 0.22; 95% CI, 0.08-0.57; P = 0.001 for multiplicative interaction), positive lymphovascular invasion (HR, 0.32; 95% CI, 0.17-0.62; P < 0.001 for multiplicative interaction), or positive lymph nodes (HR, 0.17; 95% CI, 0.07-0.38; P < 0.001 for multiplicative interaction). The survival prediction models mainly based on variables associated with chemotherapy benefits in the subgroup analysis demonstrated good calibration and discrimination, with relatively high C-indexes. The C-indexes for OS were 0.74 for patients treated with adjuvant chemotherapy and 0.70 for patients treated with postoperative observation. Two nomograms were built from the models that can calculate individualized estimates of expected net survival gain attributable to adjuvant chemotherapy. Interpretation: In this cohort study, pathologic stage IB alone was not associated with survival benefits from adjuvant chemotherapy compared with postoperative observation in patients with early-stage GC. High-risk clinicopathologic features should be considered simultaneously when evaluating patients with stage IB GC for adjuvant chemotherapy. Funding: National Natural Science Foundation of China; the National Key R&D Program of China.

4.
Materials (Basel) ; 17(4)2024 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-38399176

RESUMO

The titanium-stabilized austenitic stainless steel Fe-15Cr-15Ni, which shows enhanced resistance to irradiation swelling compared with more traditional 316Ti, has been selected as a core material for fast reactors. Data on the evolution of irradiation swelling in 15-15Ti steels at very high doses, which cannot be easily achieved by neutron irradiation, are still lacking. In this paper, the swelling behavior of the titanium-modified austenitic stainless steel 15-15Ti was investigated by pre-implantation of He at room temperature followed by Ni-ion irradiation at 580 °C to peak doses of 120, 240 and 400 dpa. Relatively small cavities were observed in the zone of helium implantation, while large cavities appeared in the region near the damage peak. A correction formula for the dpa curve was proposed and applied to samples with large swelling. It was found that the steady-state swelling rate of 15-15Ti remains at ~1%/dpa even at high doses. By comparing the swelling data of the helium-implanted and helium-free regions at same doses, 70 dpa and 122 dpa, the suppression of swelling by excessive helium can be deduced at such doses.

5.
Proc Natl Acad Sci U S A ; 121(4): e2317058121, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38232281

RESUMO

Integration of methanogenic archaea with photocatalysts presents a sustainable solution for solar-driven methanogenesis. However, maximizing CH4 conversion efficiency remains challenging due to the intrinsic energy conservation and strictly restricted substrates of methanogenic archaea. Here, we report a solar-driven biotic-abiotic hybrid (biohybrid) system by incorporating cadmium sulfide (CdS) nanoparticles with a rationally designed methanogenic archaeon Methanosarcina acetivorans C2A, in which the glucose synergist protein and glucose kinase, an energy-efficient route for glucose transport and phosphorylation from Zymomonas mobilis, were implemented to facilitate nonnative substrate glucose for methanogenesis. We demonstrate that the photo-excited electrons facilitate membrane-bound electron transport chain, thereby augmenting the Na+ and H+ ion gradients across membrane to enhance adenosine triphosphate (ATP) synthesis. Additionally, this biohybrid system promotes the metabolism of pyruvate to acetyl coenzyme A (AcCoA) and inhibits the flow of AcCoA to the tricarboxylic acid (TCA) cycle, resulting in a 1.26-fold augmentation in CH4 production from glucose-derived carbon. Our results provide a unique strategy for enhancing methanogenesis through rational biohybrid design and reprogramming, which gives a promising avenue for sustainably manufacturing value-added chemicals.


Assuntos
Trifosfato de Adenosina , Metano , Metano/metabolismo , Transporte de Elétrons , Trifosfato de Adenosina/metabolismo , Metabolismo Energético , Transporte Biológico , Methanosarcina/metabolismo
6.
Int J Nanomedicine ; 18: 6503-6525, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37965279

RESUMO

Carbon dots (CDs), a crucial component of nanomaterials, are zero-dimensional nanomaterials with carbon as the backbone structure and smaller than 10 nm. Due to their beneficial characteristics, they are widely used in biomedical fields such as biosensors, drug delivery, bio-imaging, and interactions with DNA. Interestingly, a novel type of carbon dot, generated by using herbal medicines as synthetic raw materials, has emerged as the most recent incomer in the family of CDs with the extensive growth in the number of materials selected for carbon dots synthesis. Herbal medicine-derived carbon dots (HM-CDs) have been employed in the biomedical industry, and are rapidly emerging as "modern nanomaterials" due to their unique structures and exceptional capabilities. Emerging trends suggest that their specific properties can be used in bleeding disorders, gastrointestinal disorders, inflammation-related diseases, and other common intractable diseases including cancer, menopausal syndrome, central nervous system disorders, and pain of various forms and causes. In addition, HM-CDs have been found to have organ-protective and antioxidant properties, as evidenced by extensive studies. This research provides a more comprehensive understanding of the biomedical applications of HM-CDs for the aforementioned disorders and investigates the intrinsic pharmacological activities and mechanisms of these HM-CDs to further advance their clinical applications.


Assuntos
Neoplasias , Pontos Quânticos , Humanos , Carbono/química , Pontos Quânticos/uso terapêutico , Pontos Quânticos/química , Medicina Herbária , Neoplasias/tratamento farmacológico , Extratos Vegetais
7.
Molecules ; 28(17)2023 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-37687199

RESUMO

Herbal medicines have gained recognition among physicians and patients due to their lower adverse effects compared to modern medicines. They are extensively used to treat various diseases, including cancer, cardiovascular issues, chronic inflammation, microbial contamination, diabetes, obesity, and hepatic disorders, among others. Unfortunately, the clinical application of herbal medicines is limited by their low solubility and inadequate bioavailability. Utilizing herbal medicines in the form of nanocrystals (herbal medicine nanocrystals) has shown potential in enhancing solubility and bioavailability by reducing the particle size, increasing the specific surface area, and modifying the absorption mechanisms. Multiple studies have demonstrated that these nanocrystals significantly improve drug efficacy by reducing toxicity and increasing bioavailability. This review comprehensively examines therapeutic approaches based on herbal medicine nanocrystals. It covers the preparation principles, key factors influencing nucleation and polymorphism control, applications, and limitations. The review underscores the importance of optimizing delivery systems for successful herbal medicine nanocrystal therapeutics. Furthermore, it discusses the main challenges and opportunities in developing herbal medicine nanocrystals for the purpose of treating conditions such as cancer, inflammatory diseases, cardiovascular disorders, mental and nervous diseases, and antimicrobial infections. In conclusion, we have deliberated regarding the hurdles and forthcoming outlook in the realm of nanotoxicity, in vivo kinetics, herbal ingredients as stabilizers of nanocrystals, and the potential for surmounting drug resistance through the utilization of nanocrystalline formulations in herbal medicine. We anticipate that this review will offer innovative insights into the development of herbal medicine nanocrystals as a promising and novel therapeutic strategy.


Assuntos
Nanopartículas , Plantas Medicinais , Humanos , Medicina Herbária , Disponibilidade Biológica , Extratos Vegetais
8.
Front Pharmacol ; 14: 1221069, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37693899

RESUMO

Background: Older patients with dementia always need multiple drugs due to comorbidities and cognitive impairment, further complicating drug treatment and increasing the risk of potentially inappropriate medication. The objective of our study is to estimate the global prevalence of polypharmacy and potentially inappropriate medication (PIM) and explore the factors of PIM for older patients with dementia. Methods: We searched PubMed, Embase (Ovid), and Web of Science databases to identify eligible studies from inception to 16 June 2023. We conducted a meta-analysis for observational studies reporting the prevalence of potentially inappropriate medication and polypharmacy in older patients with dementia using a random-effect model. The factors associated with PIM were meta-analyzed. Results: Overall, 62 eligible studies were included, of which 53 studies reported the prevalence of PIM and 28 studies reported the prevalence of polypharmacy. The pooled estimate of PIM and polypharmacy was 43% (95% CI 38-48) and 62% (95% CI 52-71), respectively. Sixteen studies referred to factors associated with PIM use, and 15 factors were further pooled. Polypharmacy (2.83, 95% CI 1.80-4.44), diabetes (1.31, 95% CI 1.04-1.65), heart failure (1.17, 95% CI 1.00-1.37), depression (1.45, 95% CI 1.14-1.88), history of cancer (1.20, 95% CI 1.09-1.32), hypertension (1.46, 95% CI 1.05-2.03), ischemic heart disease (1.55, 95% CI 0.77-3.12), any cardiovascular disease (1.11, 95% CI 1.06-1.17), vascular dementia (1.09, 95% CI 1.03-1.16), chronic obstructive pulmonary disease (1.39, 95% CI 1.13-1.72), and psychosis (1.91, 95% CI 1.04-3.53) are positively associated with PIM use. Conclusion: PIM and polypharmacy were highly prevalent in older patients with dementia. Among different regions, the pooled estimate of PIM use and polypharmacy varied widely. Increasing PIM in older patients with dementia was closely associated with polypharmacy. For other comorbidities such as heart failure and diabetes, prescribing should be cautioned.

10.
Neurochem Int ; 169: 105584, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37454817

RESUMO

Stroke, the third leading cause of death and disability worldwide, is classified into ischemic or hemorrhagic, in which approximately 85% of strokes are ischemic. Ischemic stroke occurs as a result of arterial occlusion due to embolus or thrombus, with ischemia in the perfusion territory supplied by the occluded artery. The traditional concept that ischemic stroke is solely a vascular occlusion disorder has been expanded to include the dynamic interaction between microglia, astrocytes, neurons, vascular cells, and matrix components forming the "neurovascular unit." Acute ischemic stroke triggers a wide spectrum of neurovascular disturbances, glial activation, and secondary neuroinflammation that promotes further injury, ultimately resulting in neuronal death. Microglia, as the resident macrophages in the central nervous system, is one of the first responders to ischemic injury and plays a significant role in post-ischemic neuroinflammation. In this review, we reviewed the mechanisms of microglia in multiple stages of post-ischemic neuroinflammation development, including acute, sub-acute and chronic phases of stroke. A comprehensive understanding of the dynamic variation and the time-dependent role of microglia in post-stroke neuroinflammation could aid in the search for more effective therapeutics and diagnostic strategies for ischemic stroke.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Microglia , Doenças Neuroinflamatórias , Acidente Vascular Cerebral/terapia , Macrófagos
11.
Adv Sci (Weinh) ; 10(26): e2302869, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37391392

RESUMO

Cadmium sulfide (CdS) buffer layer is commonly used in Kesterite Cu2 ZnSn(S,Se)4 (CZTSSe) thin film solar cells. However, the toxicity of Cadmium (Cd) and perilous waste, which is generated during the deposition process (chemical bath deposition), and the narrow bandgap (≈2.4 eV) of CdS restrict its large-scale future application. Herein, the atomic layer deposition (ALD) method is proposed to deposit zinc-tin-oxide (ZTO) as a buffer layer in Ag-doped CZTSSe solar cells. It is found that the ZTO buffer layer improves the band alignment at the Ag-CZTSSe/ZTO heterojunction interface. The smaller contact potential difference of the ZTO facilitates the extraction of charge carriers and promotes carrier transport. The better p-n junction quality helps to improve the open-circuit voltage (VOC ) and fill factor (FF). Meanwhile, the wider bandgap of ZTO assists to transfer more photons to the CZTSSe absorber, and more photocarriers are generated thus improving short-circuit current density (Jsc). Ultimately, Ag-CZTSSe/ZTO device with 10 nm thick ZTO layer and 5:1 (Zn:Sn) ratio, Sn/(Sn + Zn): 0.28 deliver a superior power conversion efficiency (PCE) of 11.8%. As far as it is known that 11.8% is the highest efficiency among Cd-free kesterite thin film solar cells.

12.
Cancer Cell Int ; 23(1): 120, 2023 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-37344821

RESUMO

Establishing appropriate preclinical models is essential for cancer research. Evidence suggests that cancer is a highly heterogeneous disease. This follows the growing use of cancer models in cancer research to avoid these differences between xenograft tumor models and patient tumors. In recent years, a patient-derived xenograft (PDX) tumor model has been actively generated and applied, which preserves both cell-cell interactions and the microenvironment of tumors by directly transplanting cancer tissue from tumors into immunodeficient mice. In addition to this, the advent of alternative hosts, such as zebrafish hosts, or in vitro models (organoids and microfluidics), has also facilitated the advancement of cancer research. However, they still have a long way to go before they become reliable models. The development of immunodeficient mice has enabled PDX to become more mature and radiate new vitality. As one of the most reliable and standard preclinical models, the PDX model in immunodeficient mice (PDX-IM) exerts important effects in drug screening, biomarker development, personalized medicine, co-clinical trials, and immunotherapy. Here, we focus on the development procedures and application of PDX-IM in detail, summarize the implications that the evolution of immunodeficient mice has brought to PDX-IM, and cover the key issues in developing PDX-IM in preclinical studies.

14.
Front Oncol ; 13: 1070343, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36923428

RESUMO

Background: PARP inhibitors (PARPis) are novel molecular targeted therapeutics for inhibition of DNA repair in tumor cells, which are commonly used in ovarian cancer. Recent case reports have indicated that haemorrhages-related adverse events may be associated with PARPis. However, little is known about the characteristics and signal strength factors of this kind of adverse event. Methods: A pharmacovigilance study from January 2004 to March 2022 based on the FDA adverse event reporting system (FAERS) database was conducted by adopting the proportional imbalance method based on the four algorithms, including the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural networks (BCPNN) and multi-item gamma Poisson shrinker (MGPS). Results: 725 cases of PARPi-haemorrhages-related adverse events were identified with a fatality rate of 4.72% (30/725) and a median age of 67 years. About 88% of the adverse events occurred within 6 months, and the median duration (IQR) was 68 days. Most adverse events (n=477, 75.11%) were related to the treatment of niraparib. Importantly, niraparib exposure was associated with a significant increase in haemorrhages-related adverse events (ROR (95% CI), 1.13(1.03,1.23), PRR (χ2), 1.12(7.32), IC (IC 025), 0.17(0.15). In addition, petechiae, gingival bleeding, bloody urine, as well as rectal haemorrhage should be monitored when using niraparib. Conclusion: Recognition and management of PARPi-haemorrhages-related adverse events is of significance to clinical practice. In this study, we provided a safety signal that haemorrhage-related adverse events should be monitored for when using niraparib. However, larger and more robust post-market safety studies are needed to improve the quality of this evidence.

15.
Artigo em Inglês | MEDLINE | ID: mdl-36880785

RESUMO

Kesterite-based Cu2ZnSnS4 (CZTS) thin-film photovoltaics involve a serious interfacial dilemma, leading to severe recombination of carriers and insufficient band alignment at the CZTS/CdS heterojunction. Herein, an interface modification scheme by aluminum doping is introduced for CZTS/CdS via a spin coating method combined with heat treatment. The thermal annealing of the kesterite/CdS junction drives the migration of doped Al from CdS to the absorber, achieving an effective ion substitution and interface passivation. This condition greatly reduces interface recombination and improves device fill factor and current density. The JSC and FF of the champion device increased from 18.01 to 22.33 mA cm-2 and 60.24 to 64.06%, respectively, owing to the optimized band alignment and remarkably enhanced charge carrier generation, separation, and transport. Consequently, a photoelectric conversion efficiency (PCE) of 8.65% was achieved, representing the highest efficiency in CZTS thin-film solar cells fabricated by pulsed laser deposition (PLD) to date. This work proposed a facile strategy for interfacial engineering treatment, opening a valuable avenue to overcome the efficiency bottleneck of CZTS thin-film solar cells.

16.
Immun Inflamm Dis ; 11(2): e765, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36840500

RESUMO

BACKGROUND: The incidence of heart failure (HF) presents an escalating trend annually, second only to cancer. Few literatures are available regarding on the role of paraoxonase 2 (PON2) in HF so far despite the protective role of PON2 in cardiovascular diseases. METHODS: PON2 expression in AC16 cells was examined with reverse transcriptase-quantitative polymerase chain reaction and western blot following angiotensin II (Ang II) challenging. After PON2 elevation, 2, 7-dichlorofluorescein diacetate assay estimated reactive oxygen species content, related kits appraised oxidative stress, enzyme-linked immunosorbent assay evaluated inflammatory levels, and Western blot was applied to the analysis of apoptosis levels. Research on cytoskeleton was conducted by immunofluorescence (IF), and Western blot analysis of the expressions of hypertrophy-related proteins was performed. BioGRID and GeneMania databases were used to analyze the relationship between PON2 and Calnexin (CANX), which was corroborated by co-immunoprecipitation experiment. Subsequently, PON2 and CANX were simultaneously overexpressed in AC16 cells induced by Ang II to further figure out the mechanism. RESULTS: PON2 expression was depleted in Ang II-induced AC16 cells. PON2 might mediate CANX/NOX4 signaling to inhibit oxidation, inflammatory, hypertrophy, and damage in Ang II-induced AC16 cells. CONCLUSION: PON2 can ease Ang II-induced cardiomyocyte injury via targeting CANX/NOX4 signaling.


Assuntos
Angiotensina II , Arildialquilfosfatase , Calnexina , Miócitos Cardíacos , NADPH Oxidase 4 , Humanos , Angiotensina II/farmacologia , Arildialquilfosfatase/metabolismo , Calnexina/metabolismo , Hipertrofia/metabolismo , Miócitos Cardíacos/metabolismo , NADPH Oxidase 4/metabolismo , Transdução de Sinais
17.
Exp Eye Res ; 229: 109416, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36801237

RESUMO

Retinal ischemia-reperfusion (I/R) injury is a common pathophysiological stress state connected to various diseases, including acute glaucoma, retinal vascular obstruction, and diabetic retinopathy. Recent studies have suggested that geranylgeranylacetone (GGA) could increase heat shock protein70 (HSP70) level and reduce retinal ganglion cells (RGCs) apoptosis in a rat retinal I/R model. However, the underlying mechanism remains unclear. Moreover, the injury caused by retinal I/R includes not only apoptosis but also autophagy and gliosis, and the effects of GGA on autophagy and gliosis have not been reported. Our study established a retinal I/R model by anterior chamber perfusion pressuring to 110 mmHg for 60 min, followed by 4 h of reperfusion. The levels of HSP70, apoptosis-related proteins, GFAP, LC3-II, and PI3K/AKT/mTOR signaling proteins were determined by western blotting and qPCR after treatment with GGA, HSP70 inhibitor quercetin (Q), PI3K inhibitor LY294002, and mTOR inhibitor rapamycin. Apoptosis was evaluated by TUNEL staining, meanwhile, HSP70 and LC3 were detected by immunofluorescence. Our results demonstrated that GGA-induced HSP70 expression significantly reduced gliosis, autophagosome accumulation, and apoptosis in retinal I/R injury, indicating that GGA exerted protective effects on retinal I/R injury. Moreover, the protective effects of GGA mechanistically relied on the activation of PI3K/AKT/mTOR signaling. In conclusion, GGA-induced HSP70 overexpression has protective effects on retinal I/R injury by activating PI3K/AKT/mTOR signaling.


Assuntos
Traumatismo por Reperfusão , Doenças Retinianas , Animais , Ratos , Apoptose , Gliose , Resposta ao Choque Térmico , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Traumatismo por Reperfusão/prevenção & controle , Traumatismo por Reperfusão/metabolismo , Doenças Retinianas/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo
18.
Int. j. morphol ; 41(1): 246-256, feb. 2023. ilus, tab
Artigo em Inglês | LILACS | ID: biblio-1430523

RESUMO

SUMMARY: This study is to investigate the effect of home-based cardiac rehabilitation (HBCR) on quality of life, functional capacity, and readmission rates in patients with heart failure. Randomized controlled trials (RCTs) were screened from Cochrane Library, CINAHL, EMBASE, and MEDLINE. The intervention group received a standardized HBCR or a comprehensive rehabilitation strategy that included HBCR. The participants in the control group received CR at a medical center or usual care without CR intervention. The main outcome measurements included quality of life, exercise capacity, mortality and re-hospitalization. This meta-analysis included 20 RCTs, in which 16 studies compared HBCR with usual care, and 4 studies compared HBCR with center-based CR. In comparison with the usual care, HBCR improved the total quality of life score [MD=-5.85, 95 % CI (-9.76, - 1.94), P=0.003, I2=75 %]. Patients with HBCR and usual care were significantly different in VO2max [MD=1.05 mL/kg/min, 95 % CI (0.35, 1.75), P=0.003, I2=46 %]. However, VO2max of patients with HBCR was not significantly different from those with center-based CR [MD=0.08 mL/kg/min, 95 % CI (-1.29, 1.44), P=0.91, I2=0 %]. There was statistically significant difference in the 6-min Walk Distance between usual care and HBCR (for distance [MD=11.84, 95 % CI (7.41, 16.28), P<0.00001, I2=0 %]; and for feet [MD=98.93, 95 % CI (26.79, 171.08), P=0.007, I2=56 %]). However, there was no significant difference in 6-min Walk Distance between patients with HBCR and center-based CR [MD=12.45, 95 % CI (-9.81, 34.72), P=0.27, I2=0 %] , or in anxiety and depression between patients with usual care and HBCR (for anxiety, [MD=-0.25, 95 % CI (-0.56, 0.05), P=0.11, I2=0 %]; for depression, [MD=-0.18, 95 % CI (-0.51, 0.16), P=0.30, I2=0 %] . No significant difference was found in death number [RR=1.04, 95 % CI (0.55, 1.98), P=0.90, I2=0 %] or in the number of re-hospitalization [RR=0.88, 95 % CI (0.66, 1.18), P=0.40, I2=0 %] between usual care and HBCR. For patients with heart failure, compare with usual care and center-based CR, HBCR can improve the total quality of life. Compare with usual care, HBCR can improve VO2max and 6-min Walk Distance, but compare with center- based CR, there are no differences in mortality, re-hospitalization rate or incidence of anxiety and depression. Additionally, center- based CR and HBCR showed similar outcomes and medical costs.


El objetivo de este estudio fue investigar el efecto de la rehabilitación cardíaca domiciliaria (HBCR) sobre la calidad de vida, la capacidad funcional y las tasas de reingreso en pacientes con insuficiencia cardíaca. Se seleccionaron ensayos controlados aleatorios (ECA) de la Biblioteca Cochrane, CINAHL, EMBASE y MEDLINE. El grupo de intervención recibió un HBCR estandarizado o una estrategia de rehabilitación integral que incluía HBCR. Los participantes del grupo de control recibieron RC en un centro médico o atención habitual sin intervención de RC. Las principales medidas de resultado incluyeron la calidad de vida, la capacidad de ejercicio, la mortalidad y la rehospitalización. Este metanálisis incluyó 20 ECA, en los que 16 estudios compararon HBCR con la atención habitual y 4 estudios compararon que mejoró la puntuación total de calidad de vida [DM=-5,85, IC del 95 % (-9,76, -1,94), P=0,003, I2=75 %]. Los pacientes con HBCR y atención habitual fueron significativamente diferentes en el VO2máx [DM = 1,05 ml/kg/ min, IC del 95 % (0,35, 1,75), P = 0,003, I2 = 46 %]. Sin embargo, el VO2max de los pacientes con HBCR no fue significativamente diferente de aquellos con CR basada en el centro [DM = 0,08 ml/kg/min, IC del 95 % (-1,29, 1,44), P = 0,91, I2 = 0 %]. Hubo una diferencia estadísticamente significativa en la distancia de caminata de 6 minutos entre la atención habitual y HBCR (para la distancia [DM=11,84, IC del 95 % (7,41, 16,28), P<0,00001, I2=0 %]; y para los pies [DM= 98,93, IC 95 % (26,79, 171,08), P=0,007, I2=56 %]). Sin embargo, no hubo una diferencia significativa en la distancia de caminata de 6 minutos entre los pacientes con HBCR y CR basada en el cen- tro [DM = 12,45, IC del 95 % (-9,81, 34,72), P = 0,27, I2 = 0 %], o en la ansiedad y depresión entre pacientes con atención habitual y HBCR (para ansiedad, [DM=-0,25, IC del 95 % (-0,56, 0,05), P=0,11, I2=0 %]; para depresión, [DM=-0,18, 95 % IC (- 0,51, 0,16), P=0,30, I2=0 %] No se encontraron diferencias significativas en el número de muertes [RR=1,04, IC del 95 % (0,55, 1,98), P=0,90, I2=0 %] o en el número de reingresos [RR=0,88, IC 95 % (0,66, 1,18), P=0,40, I2=0 %] entre atención habitual y HBCR. Para los pacientes con insuficiencia cardíaca, en comparación con la atención habitual y la CR en un centro, la HBCR puede mejorar la calidad de vida total. En comparación con la atención habitual, la HBCR puede mejorar el VO2máx y la distancia recorrida en 6 minutos, pero en comparación con la CR basada en un centro, no hay diferencias en la mortalidad, la tasa de rehospitalización o la incidencia de ansiedad y depresión. Además, CR y HBCR basados en el centro mostraron resultados y costos médicos similares.


Assuntos
Humanos , Reabilitação Cardíaca/métodos , Insuficiência Cardíaca/reabilitação , Serviços de Assistência Domiciliar , Readmissão do Paciente , Qualidade de Vida , Exercício Físico
19.
J Clin Transl Hepatol ; 11(2): 304-313, 2023 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-36643032

RESUMO

Background and Aims: Chronic hepatitis B (CHB) can cause liver fibrosis and lead to cirrhosis and cancer. As the effectiveness of antiviral therapy to reverse liver fibrosis is limited, We aimed to evaluate the effect of An-Luo-Hua-Xian pill (ALHX) on fibrosis regression in CHB patients treated with entecavir (ETV). Methods: Treatment-naïve patients with CHB were randomly treated with ETV alone or combined with ALHX (ETV+ALHX) between October 1, 2013 and December 31, 2020. Demographic, laboratory, and liver histology data before and after 78 weeks of treatment were collected. The Ishak fibrosis score (F) was used and fibrosis regression required a decrease in F of ≥1 after treatment. Results: A total of 780 patients were enrolled, and 394 with a second liver biopsy after treatment were included in the per-protocol population, 132 in ETV group and 262 in ETV+ALHX group. After 78 weeks of treatment, the fibrosis regression rate in the ETV+ALHX group was significantly higher than that of the ETV group at baseline F≥3 patients: 124/211 (58.8%) vs. 45/98 (45.9%), p=0.035. The percentage of patients with a decreased liver stiffness measurement (LSM) was higher in the ETV+ALHX group: 156/211 (73.9%) vs. 62/98 (63.%), p=0.056. Logistic regression analysis showed that ETV combined with ALHX was associated with fibrosis regression [odds ratio (OR)=1.94, p=0.018], and a family history of hepatocellular carcinoma was on the contrary. (OR=0.41, p=0.031). Conclusions: ETV combined with ALHX increased liver fibrosis regression in CHB patients.

20.
Front Oncol ; 12: 955668, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36212413

RESUMO

Background: Artificial intelligence (AI) is more and more widely used in cancer, which is of great help to doctors in diagnosis and treatment. This study aims to summarize the current research hotspots in the Application of Artificial Intelligence in Cancer (AAIC) and to assess the research trends in AAIC. Methods: Scientific publications for AAIC-related research from 1 January 1998 to 1 July 2022 were obtained from the Web of Science database. The metrics analyses using bibliometrics software included publication, keyword, author, journal, institution, and country. In addition, the blustering analysis on the binary matrix was performed on hot keywords. Results: The total number of papers in this study is 1592. The last decade of AAIC research has been divided into a slow development phase (2013-2018) and a rapid development phase (2019-2022). An international collaboration centered in the USA is dedicated to the development and application of AAIC. Li J is the most prolific writer in AAIC. Through clustering analysis and high-frequency keyword research, it has been shown that AI plays a significantly important role in the prediction, diagnosis, treatment and prognosis of cancer. Classification, diagnosis, carcinogenesis, risk, and validation are developing topics. Eight hotspot fields of AAIC were also identified. Conclusion: AAIC can benefit cancer patients in diagnosing cancer, assessing the effectiveness of treatment, making a decision, predicting prognosis and saving costs. Future AAIC research may be dedicated to optimizing AI calculation tools, improving accuracy, and promoting AI.

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