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Combined Phloretin and Human Platelet-rich Plasma Effectively Preserved Integrities of Brain Structure and Neurological Function in Rat after Traumatic Brain Damage 联合使用毛果芸香素和人血小板丰富血浆可有效保护创伤性脑损伤后大鼠脑结构和神经功能的完整性
Pub Date : 2024-01-01 DOI: 10.2174/0118761429316684240816062458
Kun-Chen Lin, Kuan-Hung Chen, Pei-Lin Shao, Han-Tan Chai, Pei-Hsun Sung, John Y Chiang, Sheung-Fat Ko, Hon-Kan Yip

Background: This study investigates whether phloretin, a brain-edema inhibitor, can enhance the therapeutic effects of human-derived platelet-rich plasma (hPRP) in reducing brain hemorrhagic volume (BHV) and preserving neurological function in rodents following acute traumatic brain damage (TBD)

Methods: Forty rats were divided into five groups: sham-control, TBD, TBD + phloretin (80 mg/kg/dose intraperitoneally at 30 minutes and on days 2/3 post-TBD), TBD + hPRP (80μL by left intra-carotid-artery injection at 3 hours post-TBD), and TBD + phloretin + hPRP. Cerebral tissues were harvested on day 28 post-TBD for analysis.

Results: Brain MRI on day 28 showed the lowest BHV in the sham-control group and the highest in the TBD group. BHV was significantly lower in the phloretin + hPRP group compared to the phloretin or hPRP alone groups, which had similar BHV. Neurological function followed an inverse pattern to BHV. By day 28, protein levels of upstream (HGMB1, TLR-2, TLR-4, MyD88, Mal, TRAM, TRIF, TRAF6, IKK-α, IKK-ß, p-NF-κB) and downstream (IL-1ß, TNF-α, iNOS) inflammation signalings, apoptosis (caspase3, PARP), and fibrosis (Smad3, TGF-ß) biomarkers, as well as flow cytometric assessment of inflammatory cells (CD11b/c+, Ly6G+, PMO+) and early (AN-V+/PI-) and late (AN-V+/PI+) mononuclear-cell apoptosis, displayed patterns similar to BHV. The number of inflammatory (CD68+, MMP9+) and brain-swelling/myelin-damaged (AQP4+, GFAP+) mediators also followed this pattern, while neuronal-myelin (Doublecortin+, NeuN, nestin) mediators showed an inverse relationship with BHV (all p<0.0001).

Conclusion: Combined phloretin and hPRP therapy is superior to either treatment alone in protecting the brain against TBD, primarily by suppressing inflammatory signaling and brain-swelling biomarkers.

研究背景本研究测试了phloretin(一种脑水肿抑制剂)是否能增强人源血小板丰富血浆(hPRP)对急性创伤性脑损伤(TBD)后啮齿类动物减轻脑出血体积(BHV)和保护神经功能的治疗作用:方法:将大鼠(n=40)分为第1组(假对照)、第2组(TBD)、第3组[TBD + phloretin(80mg/kg/dose,30分钟腹腔注射,第2/3天后TBD)、第4组(TBD + PRP/80μL,TBD后3小时左侧颈动脉内注射)和第5组(TBD + phloretin + hPRP),TBD后第28天采集脑组织:结果:第28天的脑MRI显示,第1组的BHV最低,第2组最高,第5组明显低于第3/4组,但第3/4组之间相似,而神经功能显示出各组间BHV的相反模式(所有p&amp;amp;lt;0.0001)。72 小时后,上游(HGMB1/TLR-2/TLR-4/MyD88/Mal/TRAM/TRIF/TRAF6/IKK-α/IKK-ß/p-NF-κB)和下游(IL-1ß/TNF-α/iNOS)炎症信号蛋白水平均有所下降、凋亡(caspase3/PARP)和纤维化(Smad3/TGF-ß)生物标志物以及炎症细胞(CD11b/c+//Ly6G+/PMO+)和早期(AN-V+/PI-)/晚期(AN-V+/PI+)单核细胞凋亡的流式细胞术评估显示,各组间BHV的作用方式相似(所有p&;amp;amp;lt;0.0001).炎症介质(CD68+/MMP9+)和脑肿胀/髓鞘损伤介质(AQP4+/ GFAP+)的细胞数量显示出相似的方式,而神经元-髓鞘介质(Doublecortin+/NeuN/nestin)在各组间显示出与 BHV 相反的方式(所有 p&amp;amp;lt;0.0001):结论:在保护大脑免受 TBD 侵袭方面,联合使用毛果芸香碱和 hPRP 方案的效果优于单一疗法。
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引用次数: 0
Recent Advances in the Glycolytic Processes Linked to Tumor Metastasis. 与肿瘤转移有关的糖酵解过程的最新进展。
Pub Date : 2024-01-01 DOI: 10.2174/0118761429308361240823061634
Luo Qiong, Xiao Shuyao, Xu Shan, Fu Qian, Tan Jiaying, Xiao Yao, Ling Hui

The main cause of cancer-related fatalities is cancer metastasis to other body parts, and increased glycolysis is crucial for cancer cells to maintain their elevated levels of growth and energy requirements, ultimately facilitating the invasion and spread of tumors. The Warburg effect plays a significant role in the advancement of cancer, and focusing on the suppression of aerobic glycolysis could offer a promising strategy for anti-cancer treatment. Various glycolysis processes are associated with tumor metastasis, primarily involving non-coding RNA (ncRNAs), signaling pathways, transcription factors, and more. Various categories of noncoding RNAs, including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), have shown promise in influencing glucose metabolism associated with the spread of tumors. Additionally, circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs) predominantly act as competitive endogenous RNAs (ceRNAs) by sequestering microRNAs, thereby modulating the expression of target genes and exerting significant influence on the metabolic processes of cancerous cells. Furthermore, the process of tumor metastasis through glycolysis also encompasses various signaling pathways (such as PI3K/AKT, HIF, Wnt/β- Catenin, and ERK, among others) and transcription factors. This article delineates the primary mechanisms through which non-coding RNAs, signaling pathways, and transcription factors contribute to glycolysis in tumor metastasis. It also investigates the potential use of these factors as prognostic markers and targets for cancer treatment. The manuscript also explores the innovative applications of specific traditional Chinese medicine and clinical Western medications in inhibiting tumor spread through glycolysis mechanisms, offering potential as new candidates for anti-cancer drugs.

癌症相关死亡的主要原因是癌症转移到身体其他部位,而糖酵解的增加对癌细胞维持其生长和能量需求的高水平至关重要,最终会促进肿瘤的侵袭和扩散。沃伯格效应在癌症的发展过程中起着重要作用,而重点抑制有氧糖酵解可为抗癌治疗提供一种前景广阔的策略。各种糖酵解过程都与肿瘤转移有关,主要涉及非编码 RNA(ncRNA)、信号通路、转录因子等。各类非编码 RNA,包括微 RNA(miRNA)、长非编码 RNA(lncRNA)和环状 RNA(circRNA),在影响与肿瘤扩散相关的糖代谢方面已显示出前景。此外,环状 RNA(circRNA)和长非编码 RNA(lncRNA)主要作为竞争性内源性 RNA(ceRNA),通过封存 microRNA,从而调节靶基因的表达,对癌细胞的代谢过程产生重大影响。此外,通过糖酵解实现肿瘤转移的过程还包括各种信号通路(如 PI3K/AKT、HIF、Wnt/β- Catenin 和 ERK 等)和转录因子。本文描述了非编码 RNA、信号通路和转录因子在肿瘤转移中促进糖酵解的主要机制。文章还探讨了这些因子作为预后标志物和癌症治疗靶点的潜在用途。手稿还探讨了特定中药和临床西药在通过糖酵解机制抑制肿瘤扩散方面的创新应用,为抗癌药物提供了新的候选药物潜力。
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引用次数: 0
Anticancer Properties of Baicalin against Breast Cancer and other Gynecological Cancers: Therapeutic Opportunities based on Underlying Mechanisms. 黄芩苷对乳腺癌和其他妇科癌症的抗癌特性:基于基本机制的治疗机会。
Pub Date : 2024-01-01 DOI: 10.2174/0118761429263063231204095516
Mohammad Hossein Pourhanifeh, Hossein Farrokhi-Kebria, Parsa Mostanadi, Tahereh Farkhondeh, Saeed Samarghandian

Gynecological cancers are serious life-threatening diseases responsible for high morbidity and mortality around the world. Chemotherapy, radiotherapy, and surgery are considered standard therapeutic modalities for these cancers. Since the mentioned treatments have undesirable side effects and are not effective enough, further attempts are required to explore potent complementary and/or alternative treatments. This study was designed to review and discuss the anticancer potentials of baicalin against gynecological cancers based on causal mechanisms and underlying pathways. Traditional medicine has been used for thousands of years in the therapy of diverse human diseases. The therapeutic effects of natural compounds like baicalin have been widely investigated in cancer therapy. Baicalin was effective against gynecological cancers by regulating key cellular mechanisms, including apoptosis, autophagy, and angiogenesis. Baicalin exerted its anticancer property by regulating most molecular signaling pathways, including PI3K/Akt/mTOR, NFκB, MAPK/ERK, and Wnt/β-catenin. However, more numerous experimental and clinical studies should be designed to find the efficacy of baicalin and the related mechanisms of action.

妇科癌症是严重威胁生命的疾病,在全世界都有很高的发病率和死亡率。化疗、放疗和手术被认为是治疗这些癌症的标准方法。由于上述治疗方法存在不良副作用且不够有效,因此需要进一步尝试探索有效的补充和/或替代治疗方法。本研究旨在根据黄芩苷的成因机制和潜在途径,回顾和讨论黄芩苷对妇科癌症的抗癌潜力。几千年来,传统医学一直被用于治疗人类的各种疾病。黄芩苷等天然化合物在癌症治疗中的疗效已得到广泛研究。黄芩苷通过调节关键的细胞机制,包括细胞凋亡、自噬和血管生成,对妇科癌症有效。黄芩苷通过调节大多数分子信号通路(包括 PI3K/Akt/mTOR、NFκB、MAPK/ERK 和 Wnt/β-catenin)发挥抗癌作用。然而,要找到黄芩苷的功效和相关作用机制,还需要进行更多的实验和临床研究。
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引用次数: 0
The Roles of mTOR Signaling in Nasopharyngeal Carcinoma: From Pathogenesis to Therapy mTOR信号在鼻咽癌中的作用:从发病机制到治疗
Pub Date : 2024-01-01 DOI: 10.2174/0118761429293675240709061332
Ting Gong, Gui Cao, Danyang Sun, Tongtong Ge, Ping Li

Nasopharyngeal carcinoma (NPC) is an epithelial malignancy caused by cancer of the mucosal epithelial cells of the nasopharynx. Most patients with NPC present with distant metastases and treatment resistance, both of which challenge current anti-tumour drugs. The mammalian target of the rapamycin (mTOR) signalling pathway is one of the most highly activated signalling pathways in NPC and plays an important role in various cellular activities. Dysfunction of mTOR and related signalling pathways induces tumour metabolism and growth. In this review, we summarize current evidence to evaluate the potential mechanisms by which mTOR is implicated in NPC. It was found that activating mTOR and its upstream and downstream signalling can promote tumor growth and survival of NPC. It is possible that EMT and autophagy regulated by cellular mTOR signalling activities may be implicated in the metastases and radioresistance of NPC.

鼻咽癌是一种由鼻咽粘膜上皮细胞癌变引起的上皮性恶性肿瘤。大多数鼻咽癌患者都有远处转移和耐药性,这两种情况都对目前的抗肿瘤药物提出了挑战。哺乳动物雷帕霉素靶标(mTOR)信号通路是鼻咽癌中最活跃的信号通路之一,在各种细胞活动中发挥着重要作用。mTOR及相关信号通路的功能障碍会诱导肿瘤的代谢和生长。在本综述中,我们总结了目前的证据,以评估 mTOR 与鼻咽癌相关的潜在机制。研究发现,激活 mTOR 及其上下游信号可促进鼻咽癌的肿瘤生长和存活。由细胞mTOR信号活动调控的EMT和自噬可能与鼻咽癌的转移和放射抗性有关。
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引用次数: 0
Effect of Chrysin and Chrysin Nanocrystals on Chlorpyrifos-Induced Dysfunction of the Hypothalamic-Pituitary-Testicular Axis in Rats 蛹虫草素和蛹虫草素纳米晶体对毒死蜱诱导的大鼠下丘脑-垂体-睾丸轴功能障碍的影响
Pub Date : 2024-01-01 DOI: 10.2174/0118761429305457240826093330
Tahereh Farkhondeh, Babak Roshanravan, Fariborz Samini, Saeed Samarghandian

Aims and background: The escalating global concerns regarding reproductive health underscore the urgency of investigating the impact of environmental pollutants on fertility. This study aims to focus on Chlorpyrifos (CPF), a widely-used organophosphate insecticide, and explores its adverse influence on the hypothalamic-pituitary-testicular axis in Wistar male rats. This study explores the potential protective effects of chrysin nanocrystal (CHN), a flavonoid with known antioxidant and anti-inflammatory properties, against CPF-induced impairments in male Wistar rats.

Methods: Chrysin nanocrystals were prepared using a solvent precipitation method. Six sets of male Wistar rats were subjected to 30 days of treatment, comprising a control group, a group treated solely with CPF, groups treated with CHN at doses of 5 mg/kg and 10 mg/kg, and groups co-treated with CPF and CHN. Serum levels of reproductive hormones, enzyme biomarkers of testicular function, oxidative stress, and inflammatory biomarkers were assessed. Additionally, histological examinations were conducted on the hypothalamus, testes, and epididymis.

Results: CHN exhibited antioxidant and anti-inflammatory properties, effectively counteracting CPF-induced reductions in Luteinizing Hormone (LH), serum testosterone, Follicle-Stimulating Hormone (FSH), and testicular enzyme biomarkers. Moreover, CHN enhanced antioxidant defenses, as evidenced by decreased malondialdehyde (MDA) and increased glutathione (GSH) levels in the hypothalamus, and testes, epididymis. Inflammatory markers, including nitric oxide (NO), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α), were significantly reduced in CHN co-treated groups compared to the CPF-only group. Histopathological analyses confirmed the protective effects of CHN on tissue integrity.

Conclusion: Chrysin nanocrystal demonstrated promising potential in mitigating CPF-induced reproductive deficits in male rats through its anti-inflammatory and antioxidant properties. This study provides valuable insights into therapeutic interventions against environmental toxin-induced reproductive toxicity, emphasizing the potential of chrysin nanocrystals as a protective agent in the context of CPF exposure.

目的和背景:全球对生殖健康的关注不断升级,这凸显了调查环境污染物对生育能力影响的紧迫性。本研究旨在关注一种广泛使用的有机磷杀虫剂--毒死蜱(CPF),并探讨其对 Wistar 雄性大鼠下丘脑-垂体-睾丸轴的不利影响。本研究探讨了菊黄素纳米晶体(CHN)的潜在保护作用,菊黄素纳米晶体是一种具有已知抗氧化和抗炎特性的类黄酮,可防止氯化石蜡诱导的雄性 Wistar 大鼠下丘脑-垂体-睾丸轴损伤:方法:采用溶剂沉淀法制备金黄素纳米晶体。对六组雄性 Wistar 大鼠进行为期 30 天的治疗,包括对照组、仅用氯化石蜡治疗组、用 CHN(剂量分别为 5 毫克/千克和 10 毫克/千克)治疗组以及用氯化石蜡和 CHN 联合治疗组。对血清中的生殖激素水平、睾丸功能酶生物标志物、氧化应激和炎症生物标志物进行了评估。此外,还对下丘脑、睾丸和附睾进行了组织学检查:结果:CHN 具有抗氧化和抗炎特性,能有效抵消 CPF 引起的促黄体生成素(LH)、血清睾酮、卵泡刺激素(FSH)和睾丸酶生物标志物的降低。此外,CHN 还能增强抗氧化防御能力,下丘脑、睾丸和附睾中丙二醛 (MDA) 含量的降低和谷胱甘肽 (GSH) 含量的增加都证明了这一点。与仅使用氯化石蜡组相比,联合使用 CHN 组的一氧化氮(NO)、白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)等炎症指标显著降低。组织病理学分析证实了 CHN 对组织完整性的保护作用:菊粉纳米晶体具有抗炎和抗氧化特性,在缓解氯化石蜡诱导的雄性大鼠生殖缺陷方面具有良好的潜力。这项研究为针对环境毒素引起的生殖毒性的治疗干预提供了有价值的见解,强调了纳米菊粉作为一种保护剂在氯化石蜡暴露情况下的潜力。
{"title":"Effect of Chrysin and Chrysin Nanocrystals on Chlorpyrifos-Induced Dysfunction of the Hypothalamic-Pituitary-Testicular Axis in Rats","authors":"Tahereh Farkhondeh, Babak Roshanravan, Fariborz Samini, Saeed Samarghandian","doi":"10.2174/0118761429305457240826093330","DOIUrl":"10.2174/0118761429305457240826093330","url":null,"abstract":"<p><strong>Aims and background: </strong>The escalating global concerns regarding reproductive health underscore the urgency of investigating the impact of environmental pollutants on fertility. This study aims to focus on Chlorpyrifos (CPF), a widely-used organophosphate insecticide, and explores its adverse influence on the hypothalamic-pituitary-testicular axis in Wistar male rats. This study explores the potential protective effects of chrysin nanocrystal (CHN), a flavonoid with known antioxidant and anti-inflammatory properties, against CPF-induced impairments in male Wistar rats.</p><p><strong>Methods: </strong>Chrysin nanocrystals were prepared using a solvent precipitation method. Six sets of male Wistar rats were subjected to 30 days of treatment, comprising a control group, a group treated solely with CPF, groups treated with CHN at doses of 5 mg/kg and 10 mg/kg, and groups co-treated with CPF and CHN. Serum levels of reproductive hormones, enzyme biomarkers of testicular function, oxidative stress, and inflammatory biomarkers were assessed. Additionally, histological examinations were conducted on the hypothalamus, testes, and epididymis.</p><p><strong>Results: </strong>CHN exhibited antioxidant and anti-inflammatory properties, effectively counteracting CPF-induced reductions in Luteinizing Hormone (LH), serum testosterone, Follicle-Stimulating Hormone (FSH), and testicular enzyme biomarkers. Moreover, CHN enhanced antioxidant defenses, as evidenced by decreased malondialdehyde (MDA) and increased glutathione (GSH) levels in the hypothalamus, and testes, epididymis. Inflammatory markers, including nitric oxide (NO), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α), were significantly reduced in CHN co-treated groups compared to the CPF-only group. Histopathological analyses confirmed the protective effects of CHN on tissue integrity.</p><p><strong>Conclusion: </strong>Chrysin nanocrystal demonstrated promising potential in mitigating CPF-induced reproductive deficits in male rats through its anti-inflammatory and antioxidant properties. This study provides valuable insights into therapeutic interventions against environmental toxin-induced reproductive toxicity, emphasizing the potential of chrysin nanocrystals as a protective agent in the context of CPF exposure.</p>","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142121402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Role of Local Angiotensin II/Angiotensin Type 1 Receptor in Endometriosis: A Potential Target for New Treatment Approaches 局部血管紧张素 II/血管紧张素 1 型受体在子宫内膜异位症中的作用:新治疗方法的潜在目标。
Pub Date : 2024-01-01 DOI: 10.2174/0118761429315431240712100124
Shirin Moazen, Mohammad-Hassan Arjmand

Endometriosis is a chronic inflammatory disorder described by the presence of functional endometrial-like tissues at extra-uterine locations that are related to chronic pelvic pain and infertility. Multiple molecular mechanisms, including inflammation, reactive oxygen species (ROS) generation, fibrotic reactions, and angiogenesis, are involved in the pathogenesis of endometriosis; however, the exact cause of this disorder still remains a matter of discussion. Recently, it has been shown that the local renin-angiotensin system (RAS) has been expressed in different tissues, like the gynecological tract, and alterations in its expression are associated with multiple pathological conditions like endometriosis. Angiotensin II (Ang II), as a main peptide of the RAS through angiotensin type 1 receptor (AT1R), upregulates signal transduction pathways such as nuclear factor kappa B (NF-κB), mitogen activation protein kinase (MAPK), and transforming growth factor beta (TGF-β) to promote inflammation, oxidative stress, and fibrogenesis. Angiotensin receptor blockers (ARBs) control high blood pressure, which is increased by excessive AT1R activity. Recently, it has been recognized that ARBs have tissue protective effects because of their anti-inflammatory and antifibrotic effects. In this review, we focused on the role of local Ang II/AT1R axis activity in endometriosis pathogenesis and justified the use of ARB agents as a potential therapeutic strategy to improve endometriosis.

子宫内膜异位症是一种慢性炎症性疾病,其特征是在子宫外位置存在功能性子宫内膜样组织,与慢性盆腔疼痛和不孕症有关。包括炎症、活性氧(ROS)生成、纤维化反应和血管生成在内的多种分子机制参与了子宫内膜异位症的发病机制;然而,这种疾病的确切病因仍是一个有待讨论的问题。最近的研究表明,局部肾素-血管紧张素系统(RAS)在妇科等不同组织中均有表达,其表达的改变与子宫内膜异位症等多种病症有关。血管紧张素 II(Ang II)作为 RAS 的主要肽,通过血管紧张素 1 型受体(AT1R)上调核因子卡巴 B(NF-κB)、丝裂原活化蛋白激酶(MAPK)和转化生长因子 beta(TGF-β)等信号转导通路,从而促进炎症、氧化应激和纤维增生。血管紧张素受体阻滞剂(ARB)可控制因 AT1R 活性过高而升高的高血压。最近,人们认识到血管紧张素受体阻滞剂因其抗炎和抗纤维化作用而具有组织保护作用。在这篇综述中,我们重点探讨了局部Ang II/AT1R轴活性在子宫内膜异位症发病机制中的作用,并论证了使用ARB药物作为改善子宫内膜异位症的潜在治疗策略的合理性。
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引用次数: 0
Mass Spectrometry in Covalent Drug Discovery. 质谱法在共价药物发现中的应用。
Pub Date : 2024-01-01 DOI: 10.2174/0118761429319065240605104628
Chang Liu, Xiujuan Wen
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引用次数: 0
Adipose Tissue Dysfunction Following Trauma and Hypoxia Increases the Risk of Post-Surgical Adhesion: Potential for Therapeutic Interventions 创伤和缺氧后的脂肪组织功能障碍会增加手术后粘连的风险:治疗干预的潜力。
Pub Date : 2024-01-01 DOI: 10.2174/0118761429308567240806111848
Rozita Khodashahi, Mahmoud Tavakkoli, Gorgon A Ferns, Leyla Feyzmohammadi, Amir Hossein Mirzaei, Mohsen Aliakbarian, Mohammad-Hassan Arjmand

Post-surgical adhesion is a medical challenge, especially following abdominal and pelvic surgeries. This refers to the formation of fibrotic scars that form from connective tissue in the gynecological tract or abdominal cavity. Dysfunctional adipose tissue (AT) by surgical injuries and hypoxia increases the risk of post-surgical adhesion through different molecular mechanisms. Damage-associated molecular patterns (DAMPs) and Hypoxia-induced factor 1 alpha (HIF-1α) produced during surgery trauma and hypoxia induce AT dysfunction to promote inflammation, oxidative stress, metabolic alterations, and profibrotic pathways, which contribute to post-surgical adhesions. HIF-1α and DAMPs can be considered therapeutic targets to prevent AT dysfunction and diminish the formation of adhesions in obese patients undergoing abdominal or pelvic surgeries.

手术后粘连是一项医学难题,尤其是在腹部和盆腔手术后。这是指妇科腔道或腹腔内结缔组织形成的纤维化疤痕。手术损伤和缺氧导致的脂肪组织(AT)功能失调会通过不同的分子机制增加手术后粘连的风险。手术创伤和缺氧过程中产生的损伤相关分子模式(DAMPs)和缺氧诱导因子 1α(HIF-1α)会诱发脂肪组织功能障碍,从而促进炎症、氧化应激、代谢改变和组织坏死通路,导致手术后粘连。HIF-1α和DAMPs可被视为治疗靶点,以防止腹部或盆腔手术肥胖患者的AT功能障碍并减少粘连的形成。
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引用次数: 0
The Therapeutic Potential of Targeting the Connexin43 as a New Approach to Reducing Post-surgical Adhesion 以 Connexin43 为靶点的治疗潜力是减少手术后粘连的新方法。
Pub Date : 2024-01-01 DOI: 10.2174/0118761429302171240621101944
Alireza Moslem, Rozita Khodashahi, Gordon A Ferns, Mohsen Aliakbarian, Mohammad-Hassan Arjmand

Post-surgical peritoneal adhesions are a serious problem causing complications, such as bowel obstruction, infertility, and pain. There are currently no effective ways of preventing post-surgical adhesions. Excess secretion of proinflammatory cytokines and profibrotic molecules by immune cells and adherent fibroblasts are the main mechanism that promotes post-operative fibrotic scars. Although many studies have been conducted on the pathological causes of this disorder, there are still many unknown facts in this matter, so assessment of the role of different molecules in causing inflammation and adhesion can lead to the creation of new treatment methods. Connexins are a group of proteins related to gap junctions that have a role in cell communication and transmitted signaling between adjacent cells. Between different types of connexin protein isoforms, connexin43 is known to be involved in pathological conditions related to inflammation and fibrosis. Recent studies have reported that inhibition of connexin43 has the potential to reduce inflammation and fibrosis by reducing the expression of molecules like α-SMA and plasminogen activator inhibitor (PAI) that are involved in the early stages of adhesion formation. As well as, inhibition of connexin43 may have therapeutic potential as a target to prevent post-surgical peritoneal adhesions.

手术后腹膜粘连是一个严重的问题,会导致肠梗阻、不孕和疼痛等并发症。目前还没有预防手术后粘连的有效方法。免疫细胞和粘附的成纤维细胞分泌过多的促炎细胞因子和促纤维化分子是导致术后纤维化疤痕的主要机制。尽管已经对这种疾病的病理原因进行了许多研究,但仍有许多未知的事实,因此,评估不同分子在引起炎症和粘连中的作用可有助于创造新的治疗方法。连接蛋白是一组与间隙连接有关的蛋白质,在相邻细胞间的细胞通讯和信号传递中发挥作用。在不同类型的连接蛋白异构体中,已知连接蛋白43参与了与炎症和纤维化相关的病理状况。最近的研究报告称,通过减少参与粘连形成早期阶段的 α-SMA 和纤溶酶原激活物抑制剂(PAI)等分子的表达,抑制 connexin43 有可能减轻炎症和纤维化。此外,作为预防手术后腹膜粘连的靶点,抑制 connexin43 可能具有治疗潜力。
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引用次数: 0
RBM3 Inhibits the Cell Cycle of Cutaneous Squamous Cell Carcinoma through the PI3K/AKT Signaling Pathway. RBM3 通过 PI3K/AKT 信号通路抑制皮肤鳞状细胞癌的细胞周期
Pub Date : 2024-01-01 DOI: 10.2174/0118761429323760240712050006
Yan Huang, Weichao Sun, Danli Zhu, Li Liu, Jianguo Feng, Qian Yi

Background: RBM3 is a key RNA-binding protein that has been implicated in various cellular processes, including cell proliferation and cell cycle regulation. However, its role in cutaneous squamous cell carcinoma (cSCC) remains poorly understood.

Aims: We aimed to investigate the expression levels of RNA-binding motif protein 3 (RBM3) in patients with cSCC and evaluate its effect on cell ability in cSCC and its underlying regulatory mechanisms.

Methods: The expression of RBM3 in cSCC tissues and A431 cells was determined via immunohistochemistry and western blotting. Plenti-CMV-RBM3- Puro was used to overexpress RBM3. The effect of RBM3 on the proliferation ability of cSCC cells was evaluated using MTT and colony formation assay. Cell apoptosis and cell cycle were determined using flow cytometry, while the protein expressions of BAX, NF-κB, BCL2, CASPASE 3, CYCLIN B, CYCLIN E, CDK1, phosphorylated (P)-CDK1, CDK2, P-CDK2, ERK, P-ERK, P-AMPK, AKT, P-AKT, MDM2, and P53 were assessed using western blotting.

Results: RBM3 expression was significantly downregulated in cSCC tissues and A431 cells. RBM3 overexpression significantly inhibited the cell proliferation and colony formation ability of A431. Notably, RNA-seq results showed that the differentially expressed genes associated with RBM3 were primarily involved in the regulation of the cell cycle, oocyte meiosis, and P53 signaling pathway, as well as the modulation of the MAPK, AMPK, Hippo, mTOR, PI3K/AKT, Wnt, FoxO, and NF-κB signaling pathways. Additionally, our findings demonstrated that overexpression of RBM3 inhibited cell proliferation and induced cell cycle arrest of cSCC through modulation of the PI3K/AKT signaling pathway.

Conclusion: This study provides novel insights into the suppressive roles of RBM3 in cell proliferation and the cell cycle in cSCC and highlights its therapeutic potential for cSCC.

背景:RBM3是一种关键的RNA结合蛋白,与细胞增殖和细胞周期调控等多种细胞过程有关。目的:我们旨在研究 RNA 结合图案蛋白 3(RBM3)在 cSCC 患者中的表达水平,并评估其对 cSCC 细胞能力的影响及其潜在调控机制:方法:通过免疫组化和免疫印迹法检测RBM3在cSCC组织和A431细胞中的表达。采用 Plenti-CMV-RBM3- Puro 超表达 RBM3。使用 MTT 和集落形成试验评估了 RBM3 对 cSCC 细胞增殖能力的影响。流式细胞仪测定细胞凋亡和细胞周期,Western印迹法评估 BAX、NF-κB、BCL2、CASPASE 3、CYCLIN B、CYCLIN E、CDK1、磷酸化(P)-CDK1、CDK2、P-CDK2、ERK、P-ERK、P-AMPK、AKT、P-AKT、MDM2 和 P53 的蛋白表达:结果:RBM3在cSCC组织和A431细胞中的表达明显下调。结果:RBM3 在 cSCC 组织和 A431 细胞中的表达明显下调,RBM3 的过表达明显抑制了 A431 细胞的增殖和集落形成能力。值得注意的是,RNA-seq结果显示,与RBM3相关的差异表达基因主要参与细胞周期、卵母细胞减数分裂和P53信号通路的调控,以及MAPK、AMPK、Hippo、mTOR、PI3K/AKT、Wnt、FoxO和NF-κB信号通路的调控。此外,我们的研究结果表明,过表达RBM3可通过调节PI3K/AKT信号通路抑制cSCC的细胞增殖并诱导细胞周期停滞:本研究为RBM3在cSCC细胞增殖和细胞周期中的抑制作用提供了新的见解,并突出了其治疗cSCC的潜力。
{"title":"RBM3 Inhibits the Cell Cycle of Cutaneous Squamous Cell Carcinoma through the PI3K/AKT Signaling Pathway.","authors":"Yan Huang, Weichao Sun, Danli Zhu, Li Liu, Jianguo Feng, Qian Yi","doi":"10.2174/0118761429323760240712050006","DOIUrl":"10.2174/0118761429323760240712050006","url":null,"abstract":"<p><strong>Background: </strong>RBM3 is a key RNA-binding protein that has been implicated in various cellular processes, including cell proliferation and cell cycle regulation. However, its role in cutaneous squamous cell carcinoma (cSCC) remains poorly understood.</p><p><strong>Aims: </strong>We aimed to investigate the expression levels of RNA-binding motif protein 3 (RBM3) in patients with cSCC and evaluate its effect on cell ability in cSCC and its underlying regulatory mechanisms.</p><p><strong>Methods: </strong>The expression of RBM3 in cSCC tissues and A431 cells was determined via immunohistochemistry and western blotting. Plenti-CMV-RBM3- Puro was used to overexpress RBM3. The effect of RBM3 on the proliferation ability of cSCC cells was evaluated using MTT and colony formation assay. Cell apoptosis and cell cycle were determined using flow cytometry, while the protein expressions of BAX, NF-κB, BCL2, CASPASE 3, CYCLIN B, CYCLIN E, CDK1, phosphorylated (P)-CDK1, CDK2, P-CDK2, ERK, P-ERK, P-AMPK, AKT, P-AKT, MDM2, and P53 were assessed using western blotting.</p><p><strong>Results: </strong>RBM3 expression was significantly downregulated in cSCC tissues and A431 cells. RBM3 overexpression significantly inhibited the cell proliferation and colony formation ability of A431. Notably, RNA-seq results showed that the differentially expressed genes associated with RBM3 were primarily involved in the regulation of the cell cycle, oocyte meiosis, and P53 signaling pathway, as well as the modulation of the MAPK, AMPK, Hippo, mTOR, PI3K/AKT, Wnt, FoxO, and NF-κB signaling pathways. Additionally, our findings demonstrated that overexpression of RBM3 inhibited cell proliferation and induced cell cycle arrest of cSCC through modulation of the PI3K/AKT signaling pathway.</p><p><strong>Conclusion: </strong>This study provides novel insights into the suppressive roles of RBM3 in cell proliferation and the cell cycle in cSCC and highlights its therapeutic potential for cSCC.</p>","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141750077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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Current molecular pharmacology
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