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Real-World Retention Rate, Effectiveness, and Safety of Netakimab in the Treatment of Patients with Ankylosing Spondylitis: First Year Results of the LIBRA Post-Registration Safety Study 奈达单抗治疗强直性脊柱炎患者的实际保留率、有效性和安全性:LIBRA注册后安全性研究的第一年结果。
IF 0.8 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-08-28 DOI: 10.1134/S1607672924701084
Sh. Erdes, V. I. Mazurov, I. Z. Gaydukova, O. N. Anoshenkova, I. B. Vinogradova, Yu. Yu. Grabovetskaya, S. Y. Davidian, N. A. Kiryukhina, O. E. Epifanova, L. V. Masneva, L. V. Menshikova, O. N. Mironenko, N. E. Nikulenkova, T. V. Povarova, A. N. Poliatika, R. R. Samigullina, A. E. Sizikov, I. N. Totrov, I. F. Umnova, J. V. Usacheva, A. L. Chudinov

Netakimab has shown high efficacy in controlled clinical trials in the treatment of AS patients. This article presents results of an observational study of netakimab using in routine clinical practice.

To evaluate retention rates and safety of netakimab in patients with AS in real-world clinical practice. Additionally, the efficacy of netakimab was evaluated at 1-year follow-up.

Patients were recruited for the study from August 2020 to December 2021 at 23 centers in the Russian Federation. The study included patients who were prescribed netakimab therapy before enrollment, so clinical and medical history data for the first visit were entered retrospectively, and following visits at 12, 24, and 52 weeks of therapy were collected within the study. Drug survival rate was calculated according to Kaplan–Meier analysis.

The study included 137 (93 men and 44 women) patients with AS. The average age of patients was 42.3 (11.9) years, 34.3% of patients had previously received therapy with bDMARD, mainly TNF inhibitors. At the end of the analyzed period (52 weeks of therapy), 90.4% (95% CI, 85.4-95.7) of patients continued treatment with netakimab. The BASDAI and ASDAS-CRP showed statistically significant decreases in scores from baseline at all time points. Netakimab was well tolerated by patients; AEs, related to therapy according to the investigator’s opinion, were reported in 7 (5.1%) patients. Two patients stopped taking netakimab due to AEs (terminal ileitis and chronic colitis).

In real-world clinical practice, netakimab demonstrated high retention rates, a favorable safety profile, and sustained efficacy throughout the first year of therapy.

奈达单抗在治疗强直性脊柱炎患者的对照临床试验中显示出很高的疗效。本文介绍了在常规临床实践中使用奈达单抗的观察性研究结果:目的:评估在实际临床实践中使用奈达单抗治疗强直性脊柱炎患者的保留率和安全性。此外,还对奈达单抗在1年随访中的疗效进行了评估:2020 年 8 月至 2021 年 12 月期间,在俄罗斯联邦的 23 个中心招募患者参与研究。研究对象包括入组前已接受奈达单抗治疗的患者,因此首次就诊的临床和病史数据以回顾性方式录入,并在研究范围内收集治疗 12 周、24 周和 52 周的后续就诊数据。根据卡普兰-梅耶尔分析法计算药物存活率:研究纳入了 137 名(男性 93 名,女性 44 名)强直性脊柱炎患者。患者平均年龄为42.3(11.9)岁,34.3%的患者曾接受过bDMARD治疗,主要是TNF抑制剂。在分析期结束时(治疗 52 周),90.4%(95% CI,85.4-95.7)的患者继续接受奈达单抗治疗。在所有时间点,BASDAI和ASDAS-CRP的评分与基线相比均有统计学意义上的显著下降。患者对奈达单抗的耐受性良好;根据研究者的意见,7 例(5.1%)患者出现了与治疗相关的 AE。两名患者因不良反应(末端回肠炎和慢性结肠炎)而停止服用奈达单抗:在真实世界的临床实践中,奈达单抗的保留率很高,安全性良好,在第一年的治疗中疗效持续。
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引用次数: 0
Circadian Regulation of Expression of Carotenoid Metabolism Genes (PSY2, LCYE, CrtRB1, and NCED1) in Leaves of Tomato Solanum lycopersicum L. 番茄叶中类胡萝卜素代谢基因(PSY2、LCYE、CrtRB1 和 NCED1)表达的昼夜节律调控
IF 0.8 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-08-28 DOI: 10.1134/S1607672924600611
M. A. Filyushin, A. V. Shchennikova, E. Z. Kochieva

The circadian dynamics of the expression of key genes of carotenoid metabolism (PSY2, LCYE, CrtRB1, and NCED1) in the photosynthetic tissue of tomato Solanum lycopersicum L. (cultivar Korneevsky) plants was characterized. An in silico analysis of the gene expression pattern was carried out and a high level of their transcripts was detected in the leaf tissue. qRT-PCR analysis of gene expression was performed at six time points during the day and showed the highest levels of PSY2, LCYE, and NCED1 transcripts in the second half of the light phase and CrtRB1 at the end of the dark phase. The content and composition of carotenoids in leaf tissue in the middle of the day was determined; it was shown that the leaf accumulates 1.5 times more compounds of the ɛ/β-branch of carotenoid biosynthesis pathway than compounds of the β/β-branch.

研究了类胡萝卜素代谢关键基因(PSY2、LCYE、CrtRB1 和 NCED1)在番茄 Solanum lycopersicum L. (栽培品种 Korneevsky)植株光合组织中的昼夜节律表达动态。在一天中的六个时间点对基因表达进行了 qRT-PCR 分析,结果表明 PSY2、LCYE 和 NCED1 的转录物在光照阶段的后半期含量最高,而 CrtRB1 则在暗光阶段的末期含量最高。测定了一天中叶片组织中类胡萝卜素的含量和组成;结果表明,叶片中类胡萝卜素生物合成途径ɛ/β分支化合物的积累量是β/β分支化合物的 1.5 倍。
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引用次数: 0
Aerobic Exercise Activates AMPK/PGC-1α Pathway, Inhibits Cardiomyocyte Apoptosis Improves Mitochondrial and Infarcted Heart Function 有氧运动激活 AMPK/PGC-1α 通路,抑制心肌细胞凋亡,改善线粒体和梗死心脏功能
IF 0.8 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-08-28 DOI: 10.1134/S1607672924600556
Qiu Shen, Xinyue Wu, Chuan Huang, Xinyu Ding, Chunxiao Wan

Aerobic exercise (AE) has attracted considerable research attention as a non-invasive therapeutic tool in recent years. Accumulating evidence has revealed its protective role against a wide range of diseases. In this study, we aimed to establish whether AE could inhibit apoptosis in infarcted cardiomyocytes and protect the heart. AE in post-myocardial infarction (post-MI) mice improved their cardiac and physical functions. Transmission electron microscopy of myocardial tissue and adenosine 5'-triphosphate (ATP) assay findings revealed an increased mitochondrial number but decreased ATP content in the post-MI mice. Notably, this change was significantly reversed by AE. Immunofluorescence/ TUNEL staining assay results showed that AE inhibited cardiomyocyte apoptosis. Using immunoblotting of myocardial tissues, we found that AE increased the level of the anti-apoptotic protein Bcl-2/Bax, significantly decreased the expression of the pro-apoptotic protein caspase-3, and activated the AMPK/PGC-1α signaling pathway. Our findings provide evidence that AE activates the AMPK/PGC-1α signaling pathway, improves mitochondrial energy supply capacity, and effectively inhibits apoptosis in cardiomyocytes. Therefore, AE can be considered a promising post-infarction therapeutic intervention.

近年来,有氧运动(AE)作为一种非侵入性的治疗工具吸引了大量研究人员的关注。越来越多的证据表明,有氧运动对多种疾病具有保护作用。在本研究中,我们旨在确定有氧运动是否能抑制梗死心肌细胞的凋亡并保护心脏。对心肌梗塞后(post-MI)小鼠服用 AE 可改善其心脏和身体功能。心肌梗塞后小鼠心肌组织的透射电子显微镜和腺苷-5'-三磷酸(ATP)测定结果显示,心肌梗塞后小鼠的线粒体数量增加,但ATP含量下降。值得注意的是,AE 能明显逆转这种变化。免疫荧光/TUNEL 染色检测结果显示,AE 可抑制心肌细胞凋亡。通过对心肌组织进行免疫印迹,我们发现 AE 提高了抗凋亡蛋白 Bcl-2/Bax 的水平,显著降低了促凋亡蛋白 caspase-3 的表达,并激活了 AMPK/PGC-1α 信号通路。我们的研究结果证明,AE 能激活 AMPK/PGC-1α 信号通路,提高线粒体供能能力,有效抑制心肌细胞凋亡。因此,AE 可被视为一种很有前景的梗死后治疗干预方法。
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引用次数: 0
Neuroprotective Effect of Ganoderic Acid against Focal Ischemic Stroke Induced by Middle Cerebral Artery Occlusion in the Rats via Suppression of Oxidative Stress and Inflammation 十二酸通过抑制氧化应激和炎症对大脑中动脉闭塞引起的大鼠局灶性缺血性脑卒中的神经保护作用
IF 0.8 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-07-18 DOI: 10.1134/S1607672924600313
Yong Liu, Xuemei Feng, Juan Wang, Mingfen Li

Stroke is recognized as a leading cause of disability and mortality worldwide, posing a significant challenge, particularly in developing countries. The current study aimed to evaluate the neuroprotective effect of Ganoderic acid (GA) against focal ischemic stroke in rats.

Swiss Wistar rats were used for the current study. The rats were subjected to middle cerebral artery occlusion (MCAO) to simulate transient focal ischemia, followed by reperfusion. Various neurological parameters, including infarct size, neurological deficit score, brain water content, Evans blue leakage, nitric oxide (NO), inducible nitric oxide synthase (iNOS), lactate dehydrogenase (LDH), antioxidant levels, inflammatory cytokines, apoptosis markers, inflammatory parameters, and matrix metalloproteinases (MMP) levels, were estimated. Additionally, mRNA expressions were evaluated in the brain tissue.

Dose dependently treatment of GA significantly (P < 0.001) suppressed the infarct size, neurological deflects score, brain water, evans blue leakage, NO, iNOS, LDH, C-X-C chemokine receptor type 4 (CXCR-4), monocyte chemoattractant protein-1 (MCP-1), S100 calcium-binding protein B (S-100β) and K+-Cl− cotransporter 1 (KCC1) positive cells. GA altered the level of oxidative stress parameters like Total antioxidant capacity (T-AOC), 8-hydroxy-2'-deoxyguanosine (8-OhdG), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione (GSH), malonaldehyde (MDA); cytokines viz., tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), IL-1β, IL-6, IL-9, IL-10; inflammatory parameters such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), prostaglandin (PGE2), Nuclear factor kappa B (NF-κB); apoptosis parameters like B-cell leukemia/lymphoma 2 protein (Bcl-2), Bcl-2-associated protein x (Bax), Caspase-3; matrix metallopeptidase (MMP) parameters like MMP-2, MMP-3, and MMP-9, respectively. GA remarkably suppressed the mRNA expression of TRL-4, Syndecan-1, CSF, Aquaporin-1, OCT3, and RFX1.

Ganoderic acid exhibited the protection against the cerebral ischemia reperfusion via multiple mechanism.

中风被认为是全世界致残和致死的主要原因,尤其是在发展中国家,这构成了一项重大挑战。本研究旨在评估芝麻酸(GA)对大鼠局灶性缺血性中风的神经保护作用:本研究使用瑞士 Wistar 大鼠。对大鼠进行大脑中动脉闭塞(MCAO)以模拟短暂的局灶性缺血,然后进行再灌注。研究人员估算了各种神经参数,包括脑梗塞大小、神经功能缺损评分、脑含水量、埃文斯蓝渗漏、一氧化氮(NO)、诱导型一氧化氮合酶(iNOS)、乳酸脱氢酶(LDH)、抗氧化剂水平、炎症细胞因子、细胞凋亡标志物、炎症参数和基质金属蛋白酶(MMP)水平。此外,还评估了脑组织中的 mRNA 表达:结果:GA的剂量依赖性治疗能明显(P<0.001)抑制脑梗塞大小、神经功能偏移评分、脑水、evans蓝渗漏、NO、iNOS、LDH、C-X-C趋化因子受体4型(CXCR-4)、单核细胞趋化蛋白-1(MCP-1)、S100钙结合蛋白B(S-100β)和K+-Cl-共转运体1(KCC1)阳性细胞。GA 改变了氧化应激参数的水平,如总抗氧化能力(T-AOC)、8-羟基-2'-脱氧鸟苷(8-OhdG)、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GPx)、谷胱甘肽(GSH)、丙二醛(MDA);细胞因子,即:肿瘤坏死因子-α(α-GA)、肿瘤坏死因子-α(α-GA)、肿瘤坏死因子-α(α-GA)和肿瘤坏死因子-α(α-GA)、肿瘤坏死因子-α(TNF-α)、白细胞介素-1(IL-1)、IL-1β、IL-6、IL-9、IL-10;炎症指标,如诱导型一氧化氮合酶(iNOS)、环氧化酶-2(COX-2)、前列腺素(PGE2)、核因子卡巴 B(NF-κB);凋亡参数,如 B 细胞白血病/淋巴瘤 2 蛋白(Bcl-2)、Bcl-2 相关蛋白 x(Bax)、Caspase-3;基质金属肽酶(MMP)参数,如 MMP-2、MMP-3 和 MMP-9。GA 显著抑制了 TRL-4、Syndecan-1、CSF、Aquaporin-1、OCT3 和 RFX1 的 mRNA 表达:结论:灵芝酸通过多种机制对脑缺血再灌注具有保护作用。
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引用次数: 0
Study of Radiosensitivity and Induction of Radiation Adaptive Response in Peripheral Blood Lymphocytes of Patients with Oncological Diseases Using the Micronuclear Test 利用微核试验研究肿瘤疾病患者外周血淋巴细胞的辐射敏感性和辐射适应性反应诱导。
IF 0.8 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-07-18 DOI: 10.1134/S1607672924600362
V. E. Balakin, O. M. Rozanova, N. S. Strelnikova, E. N. Smirnova, T. A. Belyakova

Radiosensitivity to low and medium doses of X-ray radiation and the ability to induce a radiation adaptive response (RAR) of lymphocytes during in vitro irradiation of peripheral blood of patients with cancer were studied. The criterion for cytogenetic damage was the frequency of micronuclei (MN) in cytochalasin-blocked binucleate lymphocytes in culture. It was found that the spontaneous level of cytogenetic damage in the lymphocytes of patients was 2.6 times higher than in healthy volunteers, and there was also significant interindividual variability in values compared to the control cohort. There were no differences in mean values for radiosensitivity to low and medium doses of X-ray between the study groups. There was no correlation between the spontaneous level of MN in lymphocytes and the radiosensitivity of individuals in both groups. RAR was induced with the same frequency and to the same extent in lymphocytes from both patients and healthy individuals.

研究了低剂量和中等剂量 X 射线辐射的放射敏感性,以及体外照射癌症患者外周血时诱导淋巴细胞产生辐射适应反应(RAR)的能力。细胞遗传损伤的标准是细胞松素阻断培养的双核淋巴细胞中出现微核(MN)的频率。研究发现,患者淋巴细胞中细胞遗传损伤的自发水平是健康志愿者的 2.6 倍,与对照组相比,个体间的数值差异也很大。研究组之间对低剂量和中等剂量 X 射线辐射敏感性的平均值没有差异。淋巴细胞中 MN 的自发水平与两组个体的辐射敏感性之间没有相关性。患者和健康人的淋巴细胞诱导 RAR 的频率和程度相同。
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引用次数: 0
The Study of TRPV1 Channels of the Central Nervous System and Their Effect on Anxiety in ICR Mice 中枢神经系统 TRPV1 通道及其对 ICR 小鼠焦虑症影响的研究
IF 0.8 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-07-18 DOI: 10.1134/S1607672924600325
V. M. Pavlov, A. Yu. Fedotova, Y. A. Andreev, V. A. Palikov, I. A. Dyachenko

The TRPV1 channel is actively involved in various neuronal processes and is found in various structures of the nervous system, including peripheral and central neurons, sensory ganglia, spinal cord, and various parts of the brain. Due to its ability to respond to various stimuli, TRPV1 can have a significant impact on the body’s responses to stress. Studies indicate the involvement of TRPV1 in the regulation of anxiety behavior. Suppression of TRPV1 activity leads to a decrease in the level of anxiety in animals, which indicates the importance of this channel in psychoemotional regulation. A promising compound for inhibiting this channel is the APHC3 peptide, which is a selective receptor antagonist. The results obtained this study show that this peptide has a pronounced anxiolytic effect, reducing the level of anxiety in the studied animals.

TRPV1 通道积极参与各种神经元过程,存在于神经系统的各种结构中,包括外周和中枢神经元、感觉神经节、脊髓和大脑的各个部分。由于 TRPV1 能够对各种刺激做出反应,因此它对人体对压力的反应有重大影响。研究表明,TRPV1 参与了焦虑行为的调节。抑制 TRPV1 的活性可降低动物的焦虑水平,这表明该通道在心理情绪调节中的重要性。APHC3 肽是一种有前景的抑制该通道的化合物,它是一种选择性受体拮抗剂。这项研究的结果表明,这种肽具有明显的抗焦虑作用,能降低研究动物的焦虑程度。
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引用次数: 0
Proinflammatory Activation of Monocytes in Patients with Immunoinflammatory Rheumatic Diseases 免疫炎症性风湿病患者单核细胞的促炎性激活。
IF 0.8 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-07-13 DOI: 10.1134/S1607672924700959
A. I. Bogatyreva, E. V. Gerasimova, T. V. Kirichenko, Yu. V. Markina, T. V. Popkova, M. V. Shalygina, T. V. Tolstik, A. M. Markin, A. N. Orekhov

The pathogenesis of immunoinflammatory rheumatic diseases (IRDs) is based on chronic inflammation, one of the key mechanisms of which may be abnormal activation of macrophages, leading to further disruption of the immune system.

. The objective of this study was to evaluate the proinflammatory activation of circulating monocytes in patients with IRDs.

. The study involved 149 participants (53 patients with rheumatoid arthritis (RA), 45 patients with systemic lupus erythematosus (SLE), 34 patients with systemic scleroderma (SSc), and 17 participants without IRDs) 30 to 65 years old. Basal and lipopolysaccharide (LPS)-stimulated secretion of monocytes was studied in a primary culture of monocytes obtained from blood by immunomagnetic separation. Quantitative assessment of the cytokines tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), as well as the chemokine monocyte chemoattractant protein-1 (MCP-1) was carried out in the culture fluid by ELISA. Proinflammatory activation of monocytes was calculated as the ratio of LPS-stimulated and basal secretions.

. It was shown that the basal secretion of all studied cytokines was significantly increased in all groups of patients with IRDs, except for the secretion of IL-1β in the SLE group, compared to the control. LPS-stimulated secretion of TNF-α was increased and MCP-1 was decreased in patients with IRDs compared to the control group; LPS-stimulated IL-1β secretion only in the SSc group significantly differed from the control group. In the RA group, monocyte activation was reduced for all cytokines compared to the control; in the SLE group, for TNF-α and MCP-1; in the SSc group, for MCP-1.

. The decrease in proinflammatory activation of monocytes in patients with IRDs is due to a high level of basal secretion of cytokines, which can lead to disruption of the adequate immune response in these diseases and is an important link in the pathogenesis of chronic inflammation.

免疫炎症性风湿病(IRDs)的发病机制以慢性炎症为基础,其关键机制之一可能是巨噬细胞的异常激活,从而导致免疫系统的进一步破坏。本研究的目的是评估 IRD 患者循环单核细胞的促炎症激活情况。这项研究涉及 149 名 30 至 65 岁的参与者(53 名类风湿性关节炎(RA)患者、45 名系统性红斑狼疮(SLE)患者、34 名系统性硬皮病(SSc)患者和 17 名无 IRD 患者)。通过免疫磁性分离从血液中获得的单核细胞原代培养物,对单核细胞的基础分泌和脂多糖(LPS)刺激分泌进行了研究。通过 ELISA 方法对培养液中的细胞因子肿瘤坏死因子α(TNF-α)、白细胞介素 1β(IL-1β)以及趋化因子单核细胞趋化蛋白-1(MCP-1)进行了定量评估。以 LPS 刺激分泌物与基础分泌物之比计算单核细胞的促炎活化。结果表明,与对照组相比,除系统性红斑狼疮组 IL-1β 的分泌外,所有研究细胞因子的基础分泌在所有 IRD 患者组中都显著增加。与对照组相比,IRDs 患者在 LPS 刺激下 TNF-α 的分泌增加,MCP-1 的分泌减少;只有 SSc 组在 LPS 刺激下 IL-1β 的分泌与对照组有明显差异。与对照组相比,RA 组单核细胞活化的所有细胞因子均减少;SLE 组单核细胞活化的 TNF-α 和 MCP-1 均减少;SSc 组单核细胞活化的 MCP-1 减少。IRD患者的单核细胞促炎激活减少是由于细胞因子的基础分泌水平较高,这会导致这些疾病的适当免疫反应被破坏,是慢性炎症发病机制中的一个重要环节。
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引用次数: 0
The 3,3'-dimethoxy-4,4'-dihydroxy-stilbene Triazole (STT) Inhibits Liver Cancer Cell Growth by Targeting Akt/mTOR Pathway 3,3'-二甲氧基-4,4'-二羟基二苯乙烯三唑(STT)通过靶向 Akt/mTOR 通路抑制肝癌细胞生长
IF 0.8 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-07-13 DOI: 10.1134/S1607672923600537
Meng Sun, Jiangtao Bai, Haisong Wang, Long Zhou, Shanfeng Li

The present study was aimed to investigate the proliferation inhibitory ability of 3,3'-dimethoxy-4,4'-dihydroxy-stilbene triazole (STT) on SNU449 and Huh7 cells. Moreover, the mechanism associated with the suppression of liver cancer cell proliferation by STT was also studied. The results revealed that STT suppresses proliferation of SNU449 and Huh7 cells to 28 and 21%, respectively treatment with 20 µM. The clonogenic survival of SNU449 and Huh7 cells was also significantly reduced after incubation with STT compared to the control cultures. In comparison to the control, STT treatment significantly decreased the invasive potential of SNU449 cells. Treatment with STT led to a prominent suppression in p62 and increase in LC3B protein expression in SNU449 cells compared to the control cells. The STT treatment dramatically decreased p-Akt and p-mTOR protein expression in SNU449 cells. Docking study revealed that STT interacts via traditional hydrogen bonding with the glutamine, phenylalanine, leucine, serine, arginine, aspartic acid, and lysine residues of Akt protein. In summary, the current study demonstrates that STT effectively suppresses the viability of SNU449 and Huh7 liver cancer cells. Moreover, STT treatment of the liver cancer cells also significantly reduces the clonogenic survival and invasive potential of SNU449 cells. Treatment of liver cancer cells with STT increases the expression of autophagic, targets anti-autophagic protein expression and down-regulates Akt/mTOR pathway to inhibit cancer growth and proliferation. Thus, STT exhibits prominent anticancer effect and needs to be investigated further as a potential candidate for the treatment of liver cancer.

本研究旨在探讨 3,3'-二甲氧基-4,4'-二羟基二苯乙烯三唑(STT)对 SNU449 和 Huh7 细胞的增殖抑制能力。此外,还研究了 STT 抑制肝癌细胞增殖的相关机制。结果显示,STT 在 20 µM 的浓度下可将 SNU449 和 Huh7 细胞的增殖率分别抑制 28% 和 21%。与对照组相比,SNU449 和 Huh7 细胞在 STT 培养后的克隆存活率也明显降低。与对照组相比,STT 处理明显降低了 SNU449 细胞的侵袭潜力。与对照组相比,STT 处理可明显抑制 SNU449 细胞中 p62 蛋白的表达,增加 LC3B 蛋白的表达。STT 处理可显著降低 SNU449 细胞中 p-Akt 和 p-mTOR 蛋白的表达。对接研究显示,STT 通过传统的氢键与 Akt 蛋白的谷氨酰胺、苯丙氨酸、亮氨酸、丝氨酸、精氨酸、天冬氨酸和赖氨酸残基相互作用。综上所述,本研究表明 STT 能有效抑制 SNU449 和 Huh7 肝癌细胞的活力。此外,用 STT 处理肝癌细胞还能显著降低 SNU449 细胞的克隆存活率和侵袭潜力。用 STT 处理肝癌细胞可增加自噬的表达、靶向抗自噬蛋白的表达并下调 Akt/mTOR 通路,从而抑制癌症的生长和增殖。因此,STT 具有显著的抗癌作用,作为治疗肝癌的潜在候选药物,有待进一步研究。
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引用次数: 0
Clinical Manifestations and Prognosis of Giant Cell Arteritis: A Retrospective Cohort Study 巨细胞动脉炎的临床表现和预后:一项回顾性队列研究
IF 0.8 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-07-13 DOI: 10.1134/S1607672924700984
E. E. Fedorinova, N. M. Bulanov, A. D. Meshkov, O. O. Borodin, I. O. Smitienko, E. V. Chachilo, A. A. Nartov, A. L. Filatova, A. V. Naumov, P. I. Novikov, S. V. Moiseev

The aim of the study was to evaluate the clinical manifestations and survival of patients with giant cell arteritis (GCA).

. A retrospective study included 166 patients with newly diagnosed GCA. Clinical, laboratory, and instrumental data and three sets of classification criteria were used to confirm the diagnosis: the American College of Rheumatology (ACR) 1990, the revised ACR criteria of 2016 and/or the new ACR and European Alliance of Rheumatologic Associations (EULAR) 2022 criteria. Some of the patients underwent instrumental investigations: temporal artery ultrasound Doppler (n = 61), contrast-enhanced computed tomography (n = 5), CT angiography (n = 6), magnetic resonance imaging (n = 4), MR angiography (n = 3), and 18F-FDG PET/CT (n = 47). Overall and recurrence-free survival rates were analyzed using survival tables and Kaplan–Meier method.

. The most frequent first manifestations of GCA were headache (81.8%), weakness (64%), fever (63.8%), and symptoms of rheumatic polymyalgia (56.6%). Changes in temporal arteries in color duplex scanning were detected in 44 out of 61 patients. GCs therapy was performed in all patients who agreed to be treated (n = 158), methotrexate was used in 49 out of 158 patients, leflunomide in 9 patients. In 45 (28.5%) out of 158 patients, a stable remission was achieved as a result of GC monotherapy; in 120 (75.9%) patients, long-term maintenance therapy with GCs was required to prevent exacerbations, including 71 (44.9%) patients in combination with methotrexate or other immunosuppressive drugs. The follow-up period of patients with a history of relapses was 21.0 (8.0–54.0) months. Relapses developed in 73 (46.2%) patients. The overall one-year survival rate was 97.1% [95% CI 94.3; 99.9], and the five-year survival rate of patients was 94.6% [95% CI 90.2; 99.0]. The one-year relapse-free survival rate was 86.4% [95% CI 80.5; 92.3], and the five-year relapse-free survival rate was 52.4% [95% CI 42.0; 62.8]. Twelve (7.2%) of 166 patients died. The cause of death was myocardial infarction in two patients, stroke in two patients, and breast cancer in one patient; in the remaining seven cases, the cause of death was not determined.

Given the high frequency of disease exacerbation, patients with GCA require long-term follow-up, especially during the first year after diagnosis.

研究旨在评估巨细胞动脉炎(GCA)患者的临床表现和存活率。一项回顾性研究纳入了 166 名新确诊的 GCA 患者。临床、实验室和仪器数据以及三套分类标准用于确诊:美国风湿病学会(ACR)1990 年标准、2016 年修订版 ACR 标准和/或 ACR 和欧洲风湿病学协会联盟(EULAR)2022 年新标准。部分患者接受了仪器检查:颞动脉超声多普勒(61例)、对比增强计算机断层扫描(5例)、CT血管造影(6例)、磁共振成像(4例)、MR血管造影(3例)和18F-FDG PET/CT(47例)。采用生存表和 Kaplan-Meier 法分析总生存率和无复发生存率。GCA最常见的首发症状是头痛(81.8%)、乏力(64%)、发热(63.8%)和风湿性多肌痛症状(56.6%)。61 名患者中有 44 人在彩色双相扫描中发现颞动脉发生变化。所有同意接受治疗的患者(158 人)都接受了转基因药物治疗,158 名患者中有 49 人使用了甲氨蝶呤,9 人使用了来氟米特。在 158 例患者中,有 45 例(28.5%)患者在接受 GC 单一疗法后病情得到稳定缓解;有 120 例(75.9%)患者需要长期接受 GCs 维持疗法以防止病情恶化,其中 71 例(44.9%)患者与甲氨蝶呤或其他免疫抑制剂联合使用。有复发史的患者的随访时间为 21.0(8.0-54.0)个月。73例(46.2%)患者复发。总的一年生存率为97.1% [95% CI 94.3; 99.9],五年生存率为94.6% [95% CI 90.2; 99.0]。一年无复发生存率为86.4% [95% CI 80.5; 92.3],五年无复发生存率为52.4% [95% CI 42.0; 62.8]。166名患者中有12人(7.2%)死亡。两名患者的死因是心肌梗死,两名患者是中风,一名患者是乳腺癌;其余七名患者的死因未确定:结论:鉴于 GCA 患者病情恶化的频率很高,需要对其进行长期随访,尤其是在确诊后的第一年。
{"title":"Clinical Manifestations and Prognosis of Giant Cell Arteritis: A Retrospective Cohort Study","authors":"E. E. Fedorinova,&nbsp;N. M. Bulanov,&nbsp;A. D. Meshkov,&nbsp;O. O. Borodin,&nbsp;I. O. Smitienko,&nbsp;E. V. Chachilo,&nbsp;A. A. Nartov,&nbsp;A. L. Filatova,&nbsp;A. V. Naumov,&nbsp;P. I. Novikov,&nbsp;S. V. Moiseev","doi":"10.1134/S1607672924700984","DOIUrl":"10.1134/S1607672924700984","url":null,"abstract":"<p>The aim of the study was to evaluate the clinical manifestations and survival of patients with giant cell arteritis (GCA).</p><p><b>.</b> A retrospective study included 166 patients with newly diagnosed GCA. Clinical, laboratory, and instrumental data and three sets of classification criteria were used to confirm the diagnosis: the American College of Rheumatology (ACR) 1990, the revised ACR criteria of 2016 and/or the new ACR and European Alliance of Rheumatologic Associations (EULAR) 2022 criteria. Some of the patients underwent instrumental investigations: temporal artery ultrasound Doppler (<i>n</i> = 61), contrast-enhanced computed tomography (<i>n</i> = 5), CT angiography (<i>n</i> = 6), magnetic resonance imaging (<i>n</i> = 4), MR angiography (<i>n</i> = 3), and 18F-FDG PET/CT (<i>n</i> = 47). Overall and recurrence-free survival rates were analyzed using survival tables and Kaplan–Meier method.</p><p><b>.</b> The most frequent first manifestations of GCA were headache (81.8%), weakness (64%), fever (63.8%), and symptoms of rheumatic polymyalgia (56.6%). Changes in temporal arteries in color duplex scanning were detected in 44 out of 61 patients. GCs therapy was performed in all patients who agreed to be treated (<i>n</i> = 158), methotrexate was used in 49 out of 158 patients, leflunomide in 9 patients. In 45 (28.5%) out of 158 patients, a stable remission was achieved as a result of GC monotherapy; in 120 (75.9%) patients, long-term maintenance therapy with GCs was required to prevent exacerbations, including 71 (44.9%) patients in combination with methotrexate or other immunosuppressive drugs. The follow-up period of patients with a history of relapses was 21.0 (8.0–54.0) months. Relapses developed in 73 (46.2%) patients. The overall one-year survival rate was 97.1% [95% CI 94.3; 99.9], and the five-year survival rate of patients was 94.6% [95% CI 90.2; 99.0]. The one-year relapse-free survival rate was 86.4% [95% CI 80.5; 92.3], and the five-year relapse-free survival rate was 52.4% [95% CI 42.0; 62.8]. Twelve (7.2%) of 166 patients died. The cause of death was myocardial infarction in two patients, stroke in two patients, and breast cancer in one patient; in the remaining seven cases, the cause of death was not determined.</p><p>Given the high frequency of disease exacerbation, patients with GCA require long-term follow-up, especially during the first year after diagnosis.</p>","PeriodicalId":529,"journal":{"name":"Doklady Biochemistry and Biophysics","volume":"517 1","pages":"250 - 258"},"PeriodicalIF":0.8,"publicationDate":"2024-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141603161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Homeotic DUX4 Genes Shape Dynamic Inter-Chromosomal Contacts with Nucleoli in Human Cells 同源 DUX4 基因在人类细胞中形成染色体间与核小体的动态联系
IF 0.8 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-07-13 DOI: 10.1134/S1607672924700935
E. S. Klushevskaya, I. R. Alembekov, Y. V. Kravatsky, N. A. Tchurikov

Nucleoli form interchromosomal contacts with genes controlling differentiation and carcinogenesis. DUX4 genes specify transcription factor possessing two homeodomains. Previously, using Circular Chromosome Conformation Capture (4С) approach on population of cells, it was demonstrated that DUX4 gene clusters form frequent contacts with nucleoli. It was found also that these contacts are almost completely abolished after heat shock treatment. 4C approach as all ligation-mediated methods is capable to detect rather close interactions between chromatin loops in nuclei. In order to independently confirm the formation and the frequency of the contacts in single cells we used FISH approach. Here, we show that DUX genes in single cells form stable contacts in all tested HEK293T cells. During heat shock, DUX4 genes reversibly move 1–3 µm away from the nuclei. We conclude that interchromosomal contacts formed by nucleoli are strong, dynamic, and reversible, providing both the initiation and maintenance of a differentiated state.

核小体与控制分化和癌变的基因形成染色体间的联系。DUX4 基因指定了具有两个同源结构域的转录因子。此前,研究人员利用环状染色体构象捕获(4С)方法对细胞群进行了研究,结果表明 DUX4 基因簇与核小体形成频繁接触。研究还发现,这些接触在热休克处理后几乎完全消失。4C 方法与所有连接介导的方法一样,能够检测细胞核中染色质环之间相当密切的相互作用。为了独立确认单细胞中接触的形成和频率,我们使用了 FISH 方法。在这里,我们发现单细胞中的 DUX 基因在所有测试的 HEK293T 细胞中都形成了稳定的接触。在热休克过程中,DUX4 基因会可逆地远离细胞核 1-3 µm。我们的结论是,核小体形成的染色体间接触是强大、动态和可逆的,可启动和维持分化状态。
{"title":"Homeotic DUX4 Genes Shape Dynamic Inter-Chromosomal Contacts with Nucleoli in Human Cells","authors":"E. S. Klushevskaya,&nbsp;I. R. Alembekov,&nbsp;Y. V. Kravatsky,&nbsp;N. A. Tchurikov","doi":"10.1134/S1607672924700935","DOIUrl":"10.1134/S1607672924700935","url":null,"abstract":"<p>Nucleoli form interchromosomal contacts with genes controlling differentiation and carcinogenesis. <i>DUX4</i> genes specify transcription factor possessing two homeodomains. Previously, using Circular Chromosome Conformation Capture (4С) approach on population of cells, it was demonstrated that <i>DUX4</i> gene clusters form frequent contacts with nucleoli. It was found also that these contacts are almost completely abolished after heat shock treatment. 4C approach as all ligation-mediated methods is capable to detect rather close interactions between chromatin loops in nuclei. In order to independently confirm the formation and the frequency of the contacts in single cells we used FISH approach. Here, we show that <i>DUX</i> genes in single cells form stable contacts in all tested HEK293T cells. During heat shock, <i>DUX4</i> genes reversibly move 1–3 µm away from the nuclei. We conclude that interchromosomal contacts formed by nucleoli are strong, dynamic, and reversible, providing both the initiation and maintenance of a differentiated state.</p>","PeriodicalId":529,"journal":{"name":"Doklady Biochemistry and Biophysics","volume":"517 1","pages":"259 - 263"},"PeriodicalIF":0.8,"publicationDate":"2024-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141603162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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