首页 > 最新文献

Biomedicines最新文献

英文 中文
Incidental Parathyroidectomy After Thyroid Surgery: A Single-Center Study. 甲状腺手术后偶发甲状旁腺切除术:单中心研究
IF 3.9 3区 工程技术 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-17 DOI: 10.3390/biomedicines12102372
Roberta Granata, Antonio Zanghì, Marianna Scribano, Giordana Riccioli, Francesca Privitera, Sandro La Vignera, Rosita Angela Condorelli, Francesco Leonforte, Antonio Mistretta, Aldo Eugenio Calogero, Massimiliano Veroux

Background: Hypoparathyroidism with hypocalcemia is the most frequent complication after thyroid surgery. Many risk factors have been involved in the development of this complication, with conflicting results. Incidental parathyroidectomy (IP) may be a frequent cause of postoperative hypocalcemia. In this study, we have evaluated the risk factors associated with the IP in a single-center cohort of patients undergoing thyroid surgery.

Patients and methods: The incidence and the risk factors for IP were evaluated in 799 patients scheduled for surgical treatment for thyroid disease between January 2018 and December 2023. Parathyroid hormone levels and serum calcium levels, together with the histological specimens, were evaluated in all patients.

Results: Post-operative temporary hypocalcemia was present in 239 (29.9%) patients. A total of 144 patients (21.9%) had an incidental parathyroidectomy. Younger patients (<40 years) had the highest risk of having an incidental parathyroidectomy (RR 1.53 (95% CI 1.084-2.161), OR 1.72 (95% CI 1.091-2.710), p = 0.014). Moreover, thyroid cancer (RR 1.4 (95 CI 1.114-1.882) OR 1.68 (95% CI 1.145-2.484), p < 0.05) and the neck dissection (RR 1.75 (95% CI 1.409-2.198) OR 2.38 (95% CI 1.644-3.460), p < 0.001) were strongly associated with the risk of incidental parathyroidectomy.

Conclusions: Younger female patients with thyroid cancer and neck dissection were at the highest risk of incidental parathyroidectomy. A meticulous surgical dissection, together with imaging methods for the detection of the parathyroid glands, may reduce the incidence of this complication.

背景:甲状旁腺功能减退伴低钙血症是甲状腺手术后最常见的并发症。许多风险因素都与这种并发症的发生有关,但结果却相互矛盾。偶然的甲状旁腺切除术(IP)可能是导致术后低钙血症的一个常见原因。在这项研究中,我们评估了单中心甲状腺手术患者队列中与IP相关的风险因素:对2018年1月至2023年12月期间计划接受甲状腺疾病手术治疗的799名患者进行了IP发生率和风险因素评估。对所有患者的甲状旁腺激素水平、血清钙水平以及组织学标本进行了评估:239名患者(29.9%)出现术后暂时性低钙血症。共有144名患者(21.9%)偶然进行了甲状旁腺切除术。患者年龄较小(P = 0.014)。此外,甲状腺癌(RR 1.4 (95 CI 1.114-1.882) OR 1.68 (95 CI 1.145-2.484),p <0.05)和颈部切除术(RR 1.75 (95 CI 1.409-2.198) OR 2.38 (95 CI 1.644-3.460),p <0.001)与偶然甲状旁腺切除术的风险密切相关:甲状腺癌和颈部切除术的年轻女性患者发生甲状旁腺切除术意外的风险最高。细致的手术切除,加上检测甲状旁腺的成像方法,可以降低这种并发症的发生率。
{"title":"Incidental Parathyroidectomy After Thyroid Surgery: A Single-Center Study.","authors":"Roberta Granata, Antonio Zanghì, Marianna Scribano, Giordana Riccioli, Francesca Privitera, Sandro La Vignera, Rosita Angela Condorelli, Francesco Leonforte, Antonio Mistretta, Aldo Eugenio Calogero, Massimiliano Veroux","doi":"10.3390/biomedicines12102372","DOIUrl":"10.3390/biomedicines12102372","url":null,"abstract":"<p><strong>Background: </strong>Hypoparathyroidism with hypocalcemia is the most frequent complication after thyroid surgery. Many risk factors have been involved in the development of this complication, with conflicting results. Incidental parathyroidectomy (IP) may be a frequent cause of postoperative hypocalcemia. In this study, we have evaluated the risk factors associated with the IP in a single-center cohort of patients undergoing thyroid surgery.</p><p><strong>Patients and methods: </strong>The incidence and the risk factors for IP were evaluated in 799 patients scheduled for surgical treatment for thyroid disease between January 2018 and December 2023. Parathyroid hormone levels and serum calcium levels, together with the histological specimens, were evaluated in all patients.</p><p><strong>Results: </strong>Post-operative temporary hypocalcemia was present in 239 (29.9%) patients. A total of 144 patients (21.9%) had an incidental parathyroidectomy. Younger patients (<40 years) had the highest risk of having an incidental parathyroidectomy (RR 1.53 (95% CI 1.084-2.161), OR 1.72 (95% CI 1.091-2.710), <i>p</i> = 0.014). Moreover, thyroid cancer (RR 1.4 (95 CI 1.114-1.882) OR 1.68 (95% CI 1.145-2.484), <i>p</i> < 0.05) and the neck dissection (RR 1.75 (95% CI 1.409-2.198) OR 2.38 (95% CI 1.644-3.460), <i>p</i> < 0.001) were strongly associated with the risk of incidental parathyroidectomy.</p><p><strong>Conclusions: </strong>Younger female patients with thyroid cancer and neck dissection were at the highest risk of incidental parathyroidectomy. A meticulous surgical dissection, together with imaging methods for the detection of the parathyroid glands, may reduce the incidence of this complication.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11505326/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Oxygen Glucose Deprivation-Induced Lactylation of H3K9 Contributes to M1 Polarization and Inflammation of Microglia Through TNF Pathway. 缺氧缺糖诱导的 H3K9 乳化有助于通过 TNF 通路实现小胶质细胞的 M1 极化和炎症。
IF 3.9 3区 工程技术 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-17 DOI: 10.3390/biomedicines12102371
Lu He, Rui Yin, Weijian Hang, Jinli Han, Juan Chen, Bin Wen, Ling Chen

Background: Hypoxia-induced M1 polarization of microglia and resultant inflammation take part in the damage caused by hypoxic-ischemic encephalopathy (HIE). Histone lactylation, a novel epigenetic modification where lactate is added to lysine residues, may play a role in HIE pathogenesis. This study investigates the role of histone lactylation in hypoxia-induced M1 microglial polarization and inflammation, aiming to provide insights for HIE treatment.

Methods: In this study, we assessed the effects of hypoxia on microglial polarization using both an HIE animal model and an oxygen-glucose deprivation cell model. Histone lactylation at various lysine residues was detected by Western blotting. Microglial polarization and inflammatory cytokines were analyzed by immunofluorescence, qPCR, and Western blotting. RNA sequencing, ChIP-qPCR, and siRNA were used to elucidate mechanisms of H3K9 lactylation.

Results: H3K9 lactylation increased due to cytoplasmic lactate during M1 polarization. Inhibiting P300 or reducing lactate dehydrogenase A expression decreased H3K9 lactylation, suppressing M1 polarization. Transcriptomic analysis indicated that H3K9 lactylation regulated M1 polarization via the TNF signaling pathway. ChIP-qPCR confirmed H3K9 lactylation enrichment at the TNFα locus, promoting OGD-induced M1 polarization and inflammation.

Conclusions: H3K9 lactylation promotes M1 polarization and inflammation via the TNF pathway, identifying it as a potential therapeutic target for neonatal HIE.

背景:缺氧诱导的小胶质细胞 M1 极化和由此产生的炎症参与了缺氧缺血性脑病(HIE)造成的损害。组蛋白乳酰化是一种新型表观遗传修饰,即在赖氨酸残基上添加乳酸,可能在 HIE 发病机制中发挥作用。本研究探讨了组蛋白乳酰化在缺氧诱导的M1小胶质细胞极化和炎症中的作用,旨在为HIE的治疗提供启示:在这项研究中,我们利用HIE动物模型和氧-葡萄糖剥夺细胞模型评估了缺氧对小胶质细胞极化的影响。通过 Western 印迹法检测了不同赖氨酸残基上的组蛋白乳酰化。通过免疫荧光、qPCR 和 Western 印迹分析了小胶质细胞极化和炎性细胞因子。利用 RNA 测序、ChIP-qPCR 和 siRNA 阐明了 H3K9 乳化的机制:结果:在M1极化过程中,细胞质乳酸导致H3K9乳酸化增加。抑制 P300 或减少乳酸脱氢酶 A 的表达可减少 H3K9 乳化,从而抑制 M1 极化。转录组分析表明,H3K9 乳酰化通过 TNF 信号通路调控 M1 极化。ChIP-qPCR证实H3K9乳酰化富集于TNFα位点,促进了OGD诱导的M1极化和炎症:结论:H3K9乳酰化通过TNF通路促进M1极化和炎症,是新生儿HIE的潜在治疗靶点。
{"title":"Oxygen Glucose Deprivation-Induced Lactylation of H3K9 Contributes to M1 Polarization and Inflammation of Microglia Through TNF Pathway.","authors":"Lu He, Rui Yin, Weijian Hang, Jinli Han, Juan Chen, Bin Wen, Ling Chen","doi":"10.3390/biomedicines12102371","DOIUrl":"10.3390/biomedicines12102371","url":null,"abstract":"<p><strong>Background: </strong>Hypoxia-induced M1 polarization of microglia and resultant inflammation take part in the damage caused by hypoxic-ischemic encephalopathy (HIE). Histone lactylation, a novel epigenetic modification where lactate is added to lysine residues, may play a role in HIE pathogenesis. This study investigates the role of histone lactylation in hypoxia-induced M1 microglial polarization and inflammation, aiming to provide insights for HIE treatment.</p><p><strong>Methods: </strong>In this study, we assessed the effects of hypoxia on microglial polarization using both an HIE animal model and an oxygen-glucose deprivation cell model. Histone lactylation at various lysine residues was detected by Western blotting. Microglial polarization and inflammatory cytokines were analyzed by immunofluorescence, qPCR, and Western blotting. RNA sequencing, ChIP-qPCR, and siRNA were used to elucidate mechanisms of H3K9 lactylation.</p><p><strong>Results: </strong>H3K9 lactylation increased due to cytoplasmic lactate during M1 polarization. Inhibiting P300 or reducing lactate dehydrogenase A expression decreased H3K9 lactylation, suppressing M1 polarization. Transcriptomic analysis indicated that H3K9 lactylation regulated M1 polarization via the TNF signaling pathway. ChIP-qPCR confirmed H3K9 lactylation enrichment at the TNFα locus, promoting OGD-induced M1 polarization and inflammation.</p><p><strong>Conclusions: </strong>H3K9 lactylation promotes M1 polarization and inflammation via the TNF pathway, identifying it as a potential therapeutic target for neonatal HIE.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11504212/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Ultrasound-Guided Venous Puncture Reduces Groin Complications in Electrophysiological Procedures. 超声引导下的静脉穿刺可减少电生理手术中的腹股沟并发症。
IF 3.9 3区 工程技术 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-17 DOI: 10.3390/biomedicines12102375
Yannick Teumer, Daniel Eckart, Lyuboslav Katov, Markus Graf, Carlo Bothner, Wolfgang Rottbauer, Karolina Weinmann-Emhardt

Background: In electrophysiological procedures, multiple punctures on the femoral vein can be necessary depending on the number of catheters required. The femoral vein is typically located indirectly by using its anatomical relationship to the artery as a reference. However, this conventional approach can lead to significant complications, including bleeding, peri-interventional transfusion, pseudoaneurysms, or arteriovenous fistulas. Despite these risks, there is limited evidence comparing the safety of ultrasound-guided venipuncture versus the conventional technique in electrophysiological procedures. Objective: This study aimed to evaluate the impact of ultrasound-guided venipuncture on vascular access complications in electrophysiological procedures and to identify associated risk factors. Methods: In this single-center trial, patients scheduled for electrophysiological procedures at Ulm University Heart Center, Germany, were enrolled between November 2021 and October 2023. Venipuncture in the groin was performed using either the conventional or an ultrasound-guided approach. The primary composite endpoint was defined as peri-interventional major vascular access complications (Bleeding Academic Research Consortium (BARC) ≥2 bleeding, pseudoaneurysms, arteriovenous fistulas, and peri-interventional transfusion) and minor complications (BARC 1). Results: A total of 1370 patients were included: 749 in the conventional group and 621 in the ultrasound group. The primary endpoint was achieved in 19.2% of the conventional group and 12.1% of the ultrasound group (p < 0.001). An increased sheath diameter and a higher number of venous accesses were identified as risk factors for the primary endpoint. Conclusions: Ultrasound guidance for venous groin puncture in electrophysiological procedures reduces access-related complications, supporting its use with careful attention to sheath size and number.

背景:在电生理手术中,根据所需导管的数量,可能需要对股静脉进行多次穿刺。通常以股静脉与动脉的解剖关系为参考,间接定位股静脉。然而,这种传统方法可能会导致严重的并发症,包括出血、围介入期输血、假性动脉瘤或动静脉瘘。尽管存在这些风险,但在电生理手术中比较超声引导静脉穿刺与传统技术的安全性的证据有限。研究目的本研究旨在评估超声引导下静脉穿刺对电生理手术中血管通路并发症的影响,并确定相关风险因素。方法:在这项单中心试验中,患者在超声引导下进行静脉穿刺:在这项单中心试验中,计划于 2021 年 11 月至 2023 年 10 月期间在德国乌尔姆大学心脏中心接受电生理手术的患者均被纳入研究范围。腹股沟静脉穿刺采用传统方法或超声引导方法。主要复合终点定义为介入期主要血管通路并发症(出血学术研究联合会(BARC)≥2出血、假性动脉瘤、动静脉瘘和介入期输血)和轻微并发症(BARC 1)。结果:共纳入 1370 名患者:常规组 749 人,超声组 621 人。19.2%的常规组和12.1%的超声组患者达到了主要终点(P < 0.001)。鞘管直径增大和静脉通路数量增加被确定为主要终点的风险因素。结论超声引导电生理手术中的腹股沟静脉穿刺可减少与入路相关的并发症,因此在使用时应注意鞘的大小和数量。
{"title":"Ultrasound-Guided Venous Puncture Reduces Groin Complications in Electrophysiological Procedures.","authors":"Yannick Teumer, Daniel Eckart, Lyuboslav Katov, Markus Graf, Carlo Bothner, Wolfgang Rottbauer, Karolina Weinmann-Emhardt","doi":"10.3390/biomedicines12102375","DOIUrl":"10.3390/biomedicines12102375","url":null,"abstract":"<p><p><b>Background</b>: In electrophysiological procedures, multiple punctures on the femoral vein can be necessary depending on the number of catheters required. The femoral vein is typically located indirectly by using its anatomical relationship to the artery as a reference. However, this conventional approach can lead to significant complications, including bleeding, peri-interventional transfusion, pseudoaneurysms, or arteriovenous fistulas. Despite these risks, there is limited evidence comparing the safety of ultrasound-guided venipuncture versus the conventional technique in electrophysiological procedures. <b>Objective</b>: This study aimed to evaluate the impact of ultrasound-guided venipuncture on vascular access complications in electrophysiological procedures and to identify associated risk factors. Methods: In this single-center trial, patients scheduled for electrophysiological procedures at Ulm University Heart Center, Germany, were enrolled between November 2021 and October 2023. Venipuncture in the groin was performed using either the conventional or an ultrasound-guided approach. The primary composite endpoint was defined as peri-interventional major vascular access complications (Bleeding Academic Research Consortium (BARC) ≥2 bleeding, pseudoaneurysms, arteriovenous fistulas, and peri-interventional transfusion) and minor complications (BARC 1). <b>Results</b>: A total of 1370 patients were included: 749 in the conventional group and 621 in the ultrasound group. The primary endpoint was achieved in 19.2% of the conventional group and 12.1% of the ultrasound group (<i>p</i> < 0.001). An increased sheath diameter and a higher number of venous accesses were identified as risk factors for the primary endpoint. <b>Conclusions</b>: Ultrasound guidance for venous groin puncture in electrophysiological procedures reduces access-related complications, supporting its use with careful attention to sheath size and number.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11504843/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A Clinical Evaluation of the Role of Autoimmunity in the Relation Between Erosions and Bone Mineral Density in Rheumatoid Arthritis. 对自身免疫在类风湿关节炎患者骨质侵蚀与骨密度关系中的作用的临床评估
IF 3.9 3区 工程技术 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-17 DOI: 10.3390/biomedicines12102376
Margaux Moret, Caroline Morizot, Marcelo de Carvalho Bittencourt, Edem Allado, Isabelle Chary-Valckenaere, Damien Loeuille

Background/objectives: Both erosions and osteoporosis in rheumatoid arthritis (RA) have common mechanisms. The aim of this study was to evaluate the relationship between erosion and bone mineral density (BMD) in RA and whether it can be driven by autoimmunity. Methods: Patients fulfilling the ACR 1987- or ACR/EULAR 2010-criteriae for RA. performed radiographs (erosions evaluated by the modified Sharp/van der Heidje erosion score) and biology for anti-citrullinated peptide antibodies (ACPAs), rheumatoid factors (RFs) and anti-nuclear antibodies (ANAs) at intervals of less than 2 years from dual-energy X-ray absorptiometry (DXA) for BMD assessment. Results: A total of 149 patients were included, (75.8% women, mean age of 62 y.o (SD 9.61) and a median disease duration of 132 months [60; 240]). A total of 61.1% patients were ACPA positive, 79.9% were erosive and 10.7% had a hip or spine T-score ≤ -2.5. A higher erosion score was associated with a lower BMD (value: -0.222; p = 0.009) and T-score (value -0.397; p < 0.0001) in the hip. ACPA status was associated with a higher erosion score (63.0 (53.2) vs. 45.5 (44.1) for ACPA- (p = 0.04)). ACPA titers were associated with a lower BMD in the hip (value -0.216; p = 0.01). In linear regression, erosion and BMD were still associated, but this association is not driven by ACPA status or titer. Conclusions: In RA patients, erosions and BMD are inversely associated but this relationship does not seem to be driven by autoimmunity only. However, the presence of ACPA or erosion should lead to osteoporosis screening.

背景/目的:类风湿性关节炎(RA)的侵蚀和骨质疏松症具有共同的机制。本研究旨在评估类风湿性关节炎的侵蚀与骨矿物质密度(BMD)之间的关系,以及这种关系是否由自身免疫驱动。研究方法对符合 ACR 1987 年或 ACR/EULAR 2010 年标准的 RA 患者进行影像学检查(用改良的 Sharp/van der Heidje 侵蚀评分法评估侵蚀情况),并在双能 X 射线吸收测定法(DXA)进行 BMD 评估后,间隔不到 2 年进行抗瓜氨酸肽抗体 (ACPA)、类风湿因子 (RF) 和抗核抗体 (ANA) 的生物学检查。结果共纳入 149 名患者(75.8% 为女性,平均年龄为 62 岁(SD 9.61),中位病程为 132 个月 [60; 240])。61.1%的患者ACPA阳性,79.9%为侵蚀性,10.7%的患者髋关节或脊柱T评分≤-2.5。侵蚀评分越高,髋部的 BMD(值:-0.222;p = 0.009)和 T 评分(值:-0.397;p < 0.0001)越低。ACPA 状态与较高的侵蚀评分相关(63.0 (53.2) vs. 45.5 (44.1) for ACPA- (p = 0.04))。ACPA 滴度与髋部较低的 BMD 相关(值为 -0.216;p = 0.01)。在线性回归中,侵蚀与 BMD 仍有关联,但这种关联并非由 ACPA 状态或滴度驱动。结论:在 RA 患者中,侵蚀与 BMD 呈反比关系,但这种关系似乎并非仅由自身免疫驱动。不过,出现 ACPA 或侵蚀时应进行骨质疏松症筛查。
{"title":"A Clinical Evaluation of the Role of Autoimmunity in the Relation Between Erosions and Bone Mineral Density in Rheumatoid Arthritis.","authors":"Margaux Moret, Caroline Morizot, Marcelo de Carvalho Bittencourt, Edem Allado, Isabelle Chary-Valckenaere, Damien Loeuille","doi":"10.3390/biomedicines12102376","DOIUrl":"10.3390/biomedicines12102376","url":null,"abstract":"<p><p><b>Background/objectives:</b> Both erosions and osteoporosis in rheumatoid arthritis (RA) have common mechanisms. The aim of this study was to evaluate the relationship between erosion and bone mineral density (BMD) in RA and whether it can be driven by autoimmunity. <b>Methods:</b> Patients fulfilling the ACR 1987- or ACR/EULAR 2010-criteriae for RA. performed radiographs (erosions evaluated by the modified Sharp/van der Heidje erosion score) and biology for anti-citrullinated peptide antibodies (ACPAs), rheumatoid factors (RFs) and anti-nuclear antibodies (ANAs) at intervals of less than 2 years from dual-energy X-ray absorptiometry (DXA) for BMD assessment. <b>Results:</b> A total of 149 patients were included, (75.8% women, mean age of 62 y.o (SD 9.61) and a median disease duration of 132 months [60; 240]). A total of 61.1% patients were ACPA positive, 79.9% were erosive and 10.7% had a hip or spine T-score ≤ -2.5. A higher erosion score was associated with a lower BMD (value: -0.222; <i>p</i> = 0.009) and T-score (value -0.397; <i>p</i> < 0.0001) in the hip. ACPA status was associated with a higher erosion score (63.0 (53.2) vs. 45.5 (44.1) for ACPA- (<i>p</i> = 0.04)). ACPA titers were associated with a lower BMD in the hip (value -0.216; <i>p</i> = 0.01). In linear regression, erosion and BMD were still associated, but this association is not driven by ACPA status or titer. <b>Conclusions</b>: In RA patients, erosions and BMD are inversely associated but this relationship does not seem to be driven by autoimmunity only. However, the presence of ACPA or erosion should lead to osteoporosis screening.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11504525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Lower Free Thyroxine Levels Are Associated with Diabetic Kidney Disease in Males with Type 2 Diabetes Mellitus: An Observational Cross-Sectional Study. 2型糖尿病男性患者游离甲状腺素水平较低与糖尿病肾病有关:一项观察性横断面研究
IF 3.9 3区 工程技术 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-17 DOI: 10.3390/biomedicines12102370
Jianan Shang, Yixuan Zheng, Meng Zhang, Meng Li, Wei Qiang, Jing Sui, Hui Guo, Bingyin Shi, Mingqian He

Objectives: We aimed to explore the correlation between thyroid function and diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM). Methods: A total of 7516 T2DM patients were enrolled and grouped according to DKD status. Clinical parameters, including blood glucose parameters, thyroid function, and indicators of renal impairment, were collected and compared between the DKD and Non-DKD groups. Correlation analysis and univariate/multivariate logistic regression analyses were performed. Results: Age, T2DM duration, the use of insulin and lipid-lowering drugs, systolic and diastolic blood pressure, body mass index, and fasting blood glucose levels were greater in the DKD group than in the Non-DKD group (p < 0.001). Notably, compared with those in the Non-DKD group, patients in the DKD group had lower triiodothyronine (T3), thyroxine (T4), free triiodothyronine (FT3), and free thyroxine (FT4) levels and higher thyrotropin levels (p < 0.001). Univariate logistic regression analysis revealed that T3, T4, FT3, and FT4 levels were negatively correlated with the risk of DKD. Spearman correlation analysis confirmed that T3, T4, FT3, and FT4 levels were negatively correlated with blood urea nitrogen levels, blood creatinine levels, and the urinary albumin-to-creatinine ratio (p < 0.05). Multivariate logistic regression analysis revealed that a greater FT4 level was a protective factor against DKD in T2DM patients, especially in males, with a cut-off value of 13.35 pmol/L (area under the curve = 0.604). Conclusions: Thyroid hormone levels, especially FT4 levels, were significantly negatively correlated with DKD in T2DM patients.

研究目的我们旨在探讨 2 型糖尿病(T2DM)患者甲状腺功能与糖尿病肾病(DKD)之间的相关性。研究方法共纳入 7516 名 T2DM 患者,并根据 DKD 状态进行分组。收集临床参数,包括血糖参数、甲状腺功能和肾功能损害指标,并在 DKD 组和非 DKD 组之间进行比较。进行了相关分析和单变量/多变量逻辑回归分析。结果显示DKD组的年龄、T2DM持续时间、胰岛素和降脂药物的使用、收缩压和舒张压、体重指数和空腹血糖水平均高于非DKD组(P < 0.001)。值得注意的是,与非 DKD 组相比,DKD 组患者的三碘甲状腺原氨酸(T3)、甲状腺素(T4)、游离三碘甲状腺原氨酸(FT3)和游离甲状腺素(FT4)水平较低,而甲状腺素水平较高(P < 0.001)。单变量逻辑回归分析显示,T3、T4、FT3 和 FT4 水平与 DKD 风险呈负相关。斯皮尔曼相关分析证实,T3、T4、FT3 和 FT4 水平与血尿素氮水平、血肌酐水平和尿白蛋白与肌酐比值呈负相关(P < 0.05)。多变量逻辑回归分析表明,FT4水平越高,对T2DM患者(尤其是男性)的DKD越有保护作用,临界值为13.35 pmol/L(曲线下面积=0.604)。结论甲状腺激素水平,尤其是 FT4 水平与 T2DM 患者的 DKD 呈显著负相关。
{"title":"Lower Free Thyroxine Levels Are Associated with Diabetic Kidney Disease in Males with Type 2 Diabetes Mellitus: An Observational Cross-Sectional Study.","authors":"Jianan Shang, Yixuan Zheng, Meng Zhang, Meng Li, Wei Qiang, Jing Sui, Hui Guo, Bingyin Shi, Mingqian He","doi":"10.3390/biomedicines12102370","DOIUrl":"10.3390/biomedicines12102370","url":null,"abstract":"<p><p><b>Objectives</b>: We aimed to explore the correlation between thyroid function and diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM). <b>Methods</b>: A total of 7516 T2DM patients were enrolled and grouped according to DKD status. Clinical parameters, including blood glucose parameters, thyroid function, and indicators of renal impairment, were collected and compared between the DKD and Non-DKD groups. Correlation analysis and univariate/multivariate logistic regression analyses were performed. <b>Results</b>: Age, T2DM duration, the use of insulin and lipid-lowering drugs, systolic and diastolic blood pressure, body mass index, and fasting blood glucose levels were greater in the DKD group than in the Non-DKD group (<i>p</i> < 0.001). Notably, compared with those in the Non-DKD group, patients in the DKD group had lower triiodothyronine (T3), thyroxine (T4), free triiodothyronine (FT3), and free thyroxine (FT4) levels and higher thyrotropin levels (<i>p</i> < 0.001). Univariate logistic regression analysis revealed that T3, T4, FT3, and FT4 levels were negatively correlated with the risk of DKD. Spearman correlation analysis confirmed that T3, T4, FT3, and FT4 levels were negatively correlated with blood urea nitrogen levels, blood creatinine levels, and the urinary albumin-to-creatinine ratio (<i>p</i> < 0.05). Multivariate logistic regression analysis revealed that a greater FT4 level was a protective factor against DKD in T2DM patients, especially in males, with a cut-off value of 13.35 pmol/L (area under the curve = 0.604). <b>Conclusions</b>: Thyroid hormone levels, especially FT4 levels, were significantly negatively correlated with DKD in T2DM patients.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11504375/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Dyslipidemia in Peritoneal Dialysis: Implications for Peritoneal Membrane Function and Patient Outcomes. 腹膜透析中的血脂异常:腹膜透析中的血脂异常:对腹膜功能和患者预后的影响。
IF 3.9 3区 工程技术 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-17 DOI: 10.3390/biomedicines12102377
Natalia Stepanova

Dyslipidemia is a common metabolic complication in patients undergoing peritoneal dialysis (PD) and has traditionally been viewed primarily in terms of cardiovascular risk. Current guidelines do not recommend initiating lipid-lowering therapy in dialysis patients due to insufficient evidence of its benefits on cardiovascular mortality. However, the impact of dyslipidemia in PD patients may extend beyond cardiovascular concerns, influencing PD-related outcomes such as the peritoneal ultrafiltration rate, residual kidney function, PD technique survival, and overall mortality. This review challenges the traditional perspective by discussing dyslipidemia's potential role in PD-related complications, which may account for the observed link between dyslipidemia and increased all-cause mortality in PD patients. It explores the pathophysiology of dyslipidemia in PD, the molecular mechanisms linking dyslipidemia to peritoneal membrane dysfunction, and summarizes clinical evidence supporting this hypothesis. In addition, this paper examines the potential for therapeutic strategies to manage dyslipidemia to improve peritoneal membrane function and patient outcomes. The review calls for future research to investigate dyslipidemia as a potential contributor to peritoneal membrane dysfunction and to develop targeted interventions for PD patients.

血脂异常是腹膜透析(PD)患者常见的代谢并发症,传统上主要从心血管风险的角度来看待。由于没有足够的证据表明降脂治疗对心血管疾病的死亡率有益,因此现行指南不建议透析患者开始降脂治疗。然而,血脂异常对透析患者的影响可能超出心血管问题的范畴,会影响腹膜超滤率、残余肾功能、透析技术存活率和总死亡率等透析相关结果。本综述挑战了传统观点,讨论了血脂异常在腹膜透析相关并发症中的潜在作用,这可能是血脂异常与腹膜透析患者全因死亡率增加之间存在关联的原因。本文探讨了腹膜透析患者血脂异常的病理生理学、血脂异常与腹膜功能障碍之间的分子机制,并总结了支持这一假设的临床证据。此外,本文还探讨了控制血脂异常以改善腹膜功能和患者预后的潜在治疗策略。该综述呼吁未来的研究将血脂异常作为腹膜功能障碍的潜在诱因进行调查,并为腹膜透析患者制定有针对性的干预措施。
{"title":"Dyslipidemia in Peritoneal Dialysis: Implications for Peritoneal Membrane Function and Patient Outcomes.","authors":"Natalia Stepanova","doi":"10.3390/biomedicines12102377","DOIUrl":"10.3390/biomedicines12102377","url":null,"abstract":"<p><p>Dyslipidemia is a common metabolic complication in patients undergoing peritoneal dialysis (PD) and has traditionally been viewed primarily in terms of cardiovascular risk. Current guidelines do not recommend initiating lipid-lowering therapy in dialysis patients due to insufficient evidence of its benefits on cardiovascular mortality. However, the impact of dyslipidemia in PD patients may extend beyond cardiovascular concerns, influencing PD-related outcomes such as the peritoneal ultrafiltration rate, residual kidney function, PD technique survival, and overall mortality. This review challenges the traditional perspective by discussing dyslipidemia's potential role in PD-related complications, which may account for the observed link between dyslipidemia and increased all-cause mortality in PD patients. It explores the pathophysiology of dyslipidemia in PD, the molecular mechanisms linking dyslipidemia to peritoneal membrane dysfunction, and summarizes clinical evidence supporting this hypothesis. In addition, this paper examines the potential for therapeutic strategies to manage dyslipidemia to improve peritoneal membrane function and patient outcomes. The review calls for future research to investigate dyslipidemia as a potential contributor to peritoneal membrane dysfunction and to develop targeted interventions for PD patients.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11505255/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Expression of Genes CYP1A1, CYP1B1, and CYP2J3 in Distinct Regions of the Heart and Its Possible Contribution to the Development of Hypertension. CYP1A1、CYP1B1 和 CYP2J3 基因在心脏不同区域的表达及其对高血压发病的可能贡献。
IF 3.9 3区 工程技术 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-17 DOI: 10.3390/biomedicines12102374
Maria L Perepechaeva, Natalia A Stefanova, Alevtina Y Grishanova, Nataliya G Kolosova

Background: It is believed that alterations in the functioning of the cytochrome P450 (CYP), which participates in metabolic transformations of endogenous polyunsaturated fatty acids (PUFAs) (with the formation of cardioprotective or cardiotoxic products), affects the development of age-related cardiovascular diseases and reduces the effectiveness of some cardioselective drugs. For example, CYP2J2 activation or CYP1B1 inhibition protects against the cardiovascular toxicity of anticancer drugs. It is currently unclear whether CYPs capable of metabolizing arachidonic acid and ω-3 PUFAs to vasodilatory and vasoconstrictive derivatives are expressed in all heart regions.

Methods: The work was performed on senescence-accelerated OXYS rats featuring elevated blood pressure, OXYSb rats (an OXYS substrain with normal blood pressure), and Wistar rats as a "healthy" control. The mRNA level was determined in the right and left ventricles, the right and left atria, and the aorta of 1-, 3-, and 12-month-old rats.

Results: We showed that all heart regions express CYPs capable of metabolizing arachidonic acid and ω-3 PUFAs and revealed significant differences between heart regions both in the mRNA level of genes CYP1B1, CYP2J3, and CYP1A1 and in the time course of expression changes with age.

Conclusions: We noticed that expression levels of these CYPs in the heart regions and aorta differ between hypertensive OXYS rats, normotensive OXYSb rats, and healthy Wistar rats but could not detect any clear-cut patterns associated with the hypertensive status of OXYS rats.

背景:细胞色素 P450(CYP)参与内源性多不饱和脂肪酸(PUFAs)的代谢转化(形成心脏保护或心脏毒性产物),其功能的改变被认为会影响与年龄相关的心血管疾病的发展,并降低某些心脏选择性药物的疗效。例如,CYP2J2 激活或 CYP1B1 抑制可防止抗癌药物对心血管的毒性。目前还不清楚,能够将花生四烯酸和ω-3 PUFAs代谢为血管舒张和血管收缩衍生物的 CYPs 是否在所有心脏区域都有表达:研究对象为血压升高的衰老加速 OXYS 大鼠、OXYSb 大鼠(血压正常的 OXYS 子品系)以及作为 "健康 "对照的 Wistar 大鼠。对 1 个月、3 个月和 12 个月大鼠的左右心室、左右心房和主动脉的 mRNA 水平进行了测定:结果:我们发现所有心脏区域都表达能代谢花生四烯酸和ω-3 PUFAs的CYPs,并发现不同心脏区域的基因CYP1B1、CYP2J3和CYP1A1的mRNA水平以及表达随年龄变化的时间过程都存在显著差异:我们注意到,这些 CYPs 在高血压 OXYS 大鼠、正常血压 OXYSb 大鼠和健康 Wistar 大鼠的心脏区域和主动脉中的表达水平存在差异,但没有发现任何与 OXYS 大鼠高血压状态相关的明确模式。
{"title":"The Expression of Genes <i>CYP1A1</i>, <i>CYP1B1</i>, and <i>CYP2J3</i> in Distinct Regions of the Heart and Its Possible Contribution to the Development of Hypertension.","authors":"Maria L Perepechaeva, Natalia A Stefanova, Alevtina Y Grishanova, Nataliya G Kolosova","doi":"10.3390/biomedicines12102374","DOIUrl":"10.3390/biomedicines12102374","url":null,"abstract":"<p><strong>Background: </strong>It is believed that alterations in the functioning of the cytochrome P450 (CYP), which participates in metabolic transformations of endogenous polyunsaturated fatty acids (PUFAs) (with the formation of cardioprotective or cardiotoxic products), affects the development of age-related cardiovascular diseases and reduces the effectiveness of some cardioselective drugs. For example, CYP2J2 activation or CYP1B1 inhibition protects against the cardiovascular toxicity of anticancer drugs. It is currently unclear whether CYPs capable of metabolizing arachidonic acid and ω-3 PUFAs to vasodilatory and vasoconstrictive derivatives are expressed in all heart regions.</p><p><strong>Methods: </strong>The work was performed on senescence-accelerated OXYS rats featuring elevated blood pressure, OXYSb rats (an OXYS substrain with normal blood pressure), and Wistar rats as a \"healthy\" control. The mRNA level was determined in the right and left ventricles, the right and left atria, and the aorta of 1-, 3-, and 12-month-old rats.</p><p><strong>Results: </strong>We showed that all heart regions express CYPs capable of metabolizing arachidonic acid and ω-3 PUFAs and revealed significant differences between heart regions both in the mRNA level of genes <i>CYP1B1</i>, <i>CYP2J3</i>, and <i>CYP1A1</i> and in the time course of expression changes with age.</p><p><strong>Conclusions: </strong>We noticed that expression levels of these CYPs in the heart regions and aorta differ between hypertensive OXYS rats, normotensive OXYSb rats, and healthy Wistar rats but could not detect any clear-cut patterns associated with the hypertensive status of OXYS rats.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11505345/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Assessing the Cost-Effectiveness of Photobiomodulation for Oral Mucositis Prevention and Treatment: A Systematic Review. 评估光生物调节用于口腔黏膜炎预防和治疗的成本效益:系统综述。
IF 3.9 3区 工程技术 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-16 DOI: 10.3390/biomedicines12102366
Susell Parra-Rojas, Juliana Cassol Spanemberg, Nerea Del Mar Díaz-Robayna, Mariela Peralta-Mamani, Rocío Trinidad Velázquez Cayón

Background: We report on the cost-effectiveness of photobiomodulation (PBM) for the prevention and treatment of oral mucositis (OM) derived from the cytotoxic effects of antineoplastic therapy.

Methods: This review followed the PRISMA 2020 guidelines. A search was conducted in PubMed, Scopus, Web of Science, Embase, and OpenGrey. Articles published before 23 July 2024, were included. Randomized controlled trials (RCTs) that included patients with head and neck cancer undergoing chemotherapy and/or radiotherapy and a placebo group compared to an intervention group (PBM) were selected. The risk of bias was evaluated using the Joanna Briggs Institute tools. The certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach and was rated as moderate.

Results: A total of 3 RCTs and 229 patients were included. PBM may represent an additional cost in the short term, but the incremental expenses derived from the cytotoxic effects of antineoplastic therapy are greater in the medium-long term. The intervention group (PBM) showed a lower incidence of severe OM compared to the control group (placebo).

Conclusions: PBM is a cost-effective long-term treatment, effective in preventing severe OM and improving the quality of life of cancer patients. More RCTs following the same standardized protocols are needed (registration CDR42024498825).

背景:我们报告了光生物调节(PBM)用于预防和治疗抗肿瘤治疗的细胞毒性作用引起的口腔黏膜炎(OM)的成本效益:本综述遵循 PRISMA 2020 指南。在 PubMed、Scopus、Web of Science、Embase 和 OpenGrey 中进行了检索。纳入了 2024 年 7 月 23 日之前发表的文章。选择的随机对照试验(RCT)包括接受化疗和/或放疗的头颈部癌症患者,以及安慰剂组与干预组(PBM)的比较。采用乔安娜-布里格斯研究所(Joanna Briggs Institute)的工具对偏倚风险进行评估。证据的确定性采用建议评估、发展和评价分级法(GRADE)进行评估,被评为中等:结果:共纳入了 3 项 RCT 和 229 名患者。PBM在短期内可能会产生额外费用,但从中长期来看,抗肿瘤治疗的细胞毒性效应所产生的增量费用更大。与对照组(安慰剂)相比,干预组(PBM)严重OM的发生率较低:结论:PBM 是一种具有成本效益的长期治疗方法,能有效预防严重 OM 并改善癌症患者的生活质量。需要按照相同的标准化方案进行更多的 RCT 研究(注册号 CDR42024498825)。
{"title":"Assessing the Cost-Effectiveness of Photobiomodulation for Oral Mucositis Prevention and Treatment: A Systematic Review.","authors":"Susell Parra-Rojas, Juliana Cassol Spanemberg, Nerea Del Mar Díaz-Robayna, Mariela Peralta-Mamani, Rocío Trinidad Velázquez Cayón","doi":"10.3390/biomedicines12102366","DOIUrl":"10.3390/biomedicines12102366","url":null,"abstract":"<p><strong>Background: </strong>We report on the cost-effectiveness of photobiomodulation (PBM) for the prevention and treatment of oral mucositis (OM) derived from the cytotoxic effects of antineoplastic therapy.</p><p><strong>Methods: </strong>This review followed the PRISMA 2020 guidelines. A search was conducted in PubMed, Scopus, Web of Science, Embase, and OpenGrey. Articles published before 23 July 2024, were included. Randomized controlled trials (RCTs) that included patients with head and neck cancer undergoing chemotherapy and/or radiotherapy and a placebo group compared to an intervention group (PBM) were selected. The risk of bias was evaluated using the Joanna Briggs Institute tools. The certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach and was rated as moderate.</p><p><strong>Results: </strong>A total of 3 RCTs and 229 patients were included. PBM may represent an additional cost in the short term, but the incremental expenses derived from the cytotoxic effects of antineoplastic therapy are greater in the medium-long term. The intervention group (PBM) showed a lower incidence of severe OM compared to the control group (placebo).</p><p><strong>Conclusions: </strong>PBM is a cost-effective long-term treatment, effective in preventing severe OM and improving the quality of life of cancer patients. More RCTs following the same standardized protocols are needed (registration CDR42024498825).</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11505555/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mitochondrial Creatine Kinase 2 (Ckmt2) as a Plasma-Based Biomarker for Evaluating Reperfusion Injury in Acute Myocardial Infarction. 线粒体肌酸激酶 2 (Ckmt2) 作为评估急性心肌梗死再灌注损伤的血浆生物标记物。
IF 3.9 3区 工程技术 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-16 DOI: 10.3390/biomedicines12102368
Alexander Lang, Daniel Oehler, Marcel Benkhoff, Yvonne Reinders, Maike Barcik, Khatereh Shahrjerdi, Madlen Kaldirim, Albert Sickmann, Lisa Dannenberg, Amin Polzin, Susanne Pfeiler, Malte Kelm, Maria Grandoch, Christian Jung, Norbert Gerdes

Background/objectives: Acute myocardial infarction (AMI), characterized by irreversible heart muscle damage and impaired cardiac function caused by myocardial ischemia, is a leading cause of global mortality. The damage associated with reperfusion, particularly mitochondrial dysfunction and reactive oxygen species (ROS) formation, has emerged as a crucial factor in the pathogenesis of cardiac diseases, leading to the recognition of mitochondrial proteins as potential markers for myocardial damage. This study aimed to identify differentially expressed proteins based on the type of cardiac injury, in particular those with and without reperfusion.

Methods: Male C57Bl/6J mice were either left untreated, sham-operated, received non-reperfused AMI, or reperfused AMI. Twenty-four hours after the procedures, left ventricular (LV) function and morphological changes including infarct size were determined using echocardiography and triphenyl tetrazolium chloride (TTC) staining, respectively. In addition, plasma was isolated and subjected to untargeted mass spectrometry and, further on, the ELISA-based validation of candidate proteins.

Results: We identified mitochondrial creatine kinase 2 (Ckmt2) as a differentially regulated protein in plasma of mice with reperfused but not non-reperfused AMI. Elevated levels of Ckmt2 were significantly associated with infarct size and impaired LV function following reperfused AMI, suggesting a specific involvement in reperfusion damage.

Conclusions: Our study highlights the potential of plasma Ckmt2 as a biomarker for assessing reperfusion injury and its impact on cardiac function and morphology in the acute phase of MI.

背景/目的:急性心肌梗死(AMI)的特点是心肌缺血造成不可逆的心肌损伤和心功能受损,是导致全球死亡的主要原因。与再灌注相关的损伤,尤其是线粒体功能障碍和活性氧(ROS)的形成,已成为心脏疾病发病机制中的一个关键因素,从而导致线粒体蛋白被认为是心肌损伤的潜在标志物。本研究旨在根据心脏损伤的类型,特别是有再灌注和无再灌注的类型,确定不同表达的蛋白质:雄性 C57Bl/6J 小鼠未经处理、假手术、接受非再灌注急性心肌梗死或再灌注急性心肌梗死。术后 24 小时,分别用超声心动图和三苯基氯化四氮唑(TTC)染色法测定左心室(LV)功能和形态学变化(包括梗死面积)。此外,我们还分离了血浆并对其进行了非靶向质谱分析,并进一步对候选蛋白质进行了基于酶联免疫吸附的验证:结果:我们发现线粒体肌酸激酶2(Ckmt2)是再灌注而非再灌注AMI小鼠血浆中受到不同调控的蛋白质。Ckmt2水平的升高与急性心肌梗死再灌注后的梗死面积和左心室功能受损显著相关,这表明Ckmt2特别参与了再灌注损伤:我们的研究强调了血浆 Ckmt2 作为生物标记物的潜力,可用于评估再灌注损伤及其对心肌梗死急性期心脏功能和形态的影响。
{"title":"Mitochondrial Creatine Kinase 2 (Ckmt2) as a Plasma-Based Biomarker for Evaluating Reperfusion Injury in Acute Myocardial Infarction.","authors":"Alexander Lang, Daniel Oehler, Marcel Benkhoff, Yvonne Reinders, Maike Barcik, Khatereh Shahrjerdi, Madlen Kaldirim, Albert Sickmann, Lisa Dannenberg, Amin Polzin, Susanne Pfeiler, Malte Kelm, Maria Grandoch, Christian Jung, Norbert Gerdes","doi":"10.3390/biomedicines12102368","DOIUrl":"10.3390/biomedicines12102368","url":null,"abstract":"<p><strong>Background/objectives: </strong>Acute myocardial infarction (AMI), characterized by irreversible heart muscle damage and impaired cardiac function caused by myocardial ischemia, is a leading cause of global mortality. The damage associated with reperfusion, particularly mitochondrial dysfunction and reactive oxygen species (ROS) formation, has emerged as a crucial factor in the pathogenesis of cardiac diseases, leading to the recognition of mitochondrial proteins as potential markers for myocardial damage. This study aimed to identify differentially expressed proteins based on the type of cardiac injury, in particular those with and without reperfusion.</p><p><strong>Methods: </strong>Male C57Bl/6J mice were either left untreated, sham-operated, received non-reperfused AMI, or reperfused AMI. Twenty-four hours after the procedures, left ventricular (LV) function and morphological changes including infarct size were determined using echocardiography and triphenyl tetrazolium chloride (TTC) staining, respectively. In addition, plasma was isolated and subjected to untargeted mass spectrometry and, further on, the ELISA-based validation of candidate proteins.</p><p><strong>Results: </strong>We identified mitochondrial creatine kinase 2 (Ckmt2) as a differentially regulated protein in plasma of mice with reperfused but not non-reperfused AMI. Elevated levels of Ckmt2 were significantly associated with infarct size and impaired LV function following reperfused AMI, suggesting a specific involvement in reperfusion damage.</p><p><strong>Conclusions: </strong>Our study highlights the potential of plasma Ckmt2 as a biomarker for assessing reperfusion injury and its impact on cardiac function and morphology in the acute phase of MI.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11504053/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Systemic Innate Immune System Restoration as a Therapeutic Approach for Neurodegenerative Disease: Effects of NP001 on Amyotrophic Lateral Sclerosis (ALS) Progression. 系统性先天性免疫系统恢复作为神经退行性疾病的一种治疗方法:NP001对肌萎缩性脊髓侧索硬化症(ALS)进展的影响
IF 3.9 3区 工程技术 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-16 DOI: 10.3390/biomedicines12102362
Michael S McGrath, Rongzhen Zhang, Paige M Bracci, Ari Azhir, Bruce D Forrest

Background/objective: Amyotrophic lateral sclerosis (ALS) is a diagnosis that incorporates a heterogeneous set of neurodegenerative processes into a single progressive and uniformly fatal disease making the development of a uniformly applicable therapeutic difficult. Recent multinational ALS natural history incidence studies have identified systemic chronic activation of the innate immune system as a major risk factor for developing ALS. Persistent immune activation in patients with ALS leads to loss of muscle and lowering of serum creatinine. The goal of the current study was to test whether the slowing of nerve and muscle destruction in NP001-treated ALS patients compared with controls in phase 2 studies would lead to extension of survival.

Methods: Phase 2 clinical studies with NP001, an intravenously administered form of the innate immune system regulator NaClO2, are now reporting long-term survival benefits for drug recipients vs. placebo controls after only six months of intermittent treatment. As a prodrug, NP001 is converted by macrophages to taurine chloramine, a long-lived regulator of inflammation. We performed a pooled analysis of all patients who had completed the studies in two six-month NP001 phase 2 trials. Changes in respiratory vital capacity and the muscle mass product, creatinine, defined treated patients who, compared to placebo, had up to a year of extended survival.

Conclusions: The observed longer survival in ALS patients with the greatest inflammation-associated muscle loss provides further evidence that ALS is a disease of ongoing innate immune dysfunction and that NP001 is a disease-modifying drug with sustained clinical activity.

背景/目的:肌萎缩性脊髓侧索硬化症(ALS)是一种将多种神经退行性病变过程整合为单一的渐进性和致命性疾病的诊断方法,因此很难开发出统一适用的疗法。最近的多国 ALS 自然史发病率研究发现,先天性免疫系统的系统性慢性激活是 ALS 发病的主要风险因素。ALS 患者体内持续的免疫激活会导致肌肉萎缩和血清肌酐降低。本研究的目的是测试在二期研究中,与对照组相比,NP001治疗ALS患者的神经和肌肉破坏速度减慢是否会导致生存期延长:NP001是一种先天性免疫系统调节剂NaClO2的静脉给药形式,目前进行的2期临床研究报告显示,与安慰剂对照组相比,接受药物治疗的患者仅在6个月的间歇治疗后就获得了长期生存的益处。作为一种原药,NP001 会被巨噬细胞转化为牛磺酸氯胺,这是一种长效的炎症调节剂。我们对两项为期 6 个月的 NP001 2 期试验中完成研究的所有患者进行了汇总分析。与安慰剂相比,接受治疗的患者生存期最长可延长一年:在炎症相关肌肉损失最大的 ALS 患者中观察到的更长生存期进一步证明了 ALS 是一种持续存在先天性免疫功能障碍的疾病,而 NP001 是一种具有持续临床活性的疾病调节药物。
{"title":"Systemic Innate Immune System Restoration as a Therapeutic Approach for Neurodegenerative Disease: Effects of NP001 on Amyotrophic Lateral Sclerosis (ALS) Progression.","authors":"Michael S McGrath, Rongzhen Zhang, Paige M Bracci, Ari Azhir, Bruce D Forrest","doi":"10.3390/biomedicines12102362","DOIUrl":"10.3390/biomedicines12102362","url":null,"abstract":"<p><strong>Background/objective: </strong>Amyotrophic lateral sclerosis (ALS) is a diagnosis that incorporates a heterogeneous set of neurodegenerative processes into a single progressive and uniformly fatal disease making the development of a uniformly applicable therapeutic difficult. Recent multinational ALS natural history incidence studies have identified systemic chronic activation of the innate immune system as a major risk factor for developing ALS. Persistent immune activation in patients with ALS leads to loss of muscle and lowering of serum creatinine. The goal of the current study was to test whether the slowing of nerve and muscle destruction in NP001-treated ALS patients compared with controls in phase 2 studies would lead to extension of survival.</p><p><strong>Methods: </strong>Phase 2 clinical studies with NP001, an intravenously administered form of the innate immune system regulator NaClO<sub>2</sub>, are now reporting long-term survival benefits for drug recipients vs. placebo controls after only six months of intermittent treatment. As a prodrug, NP001 is converted by macrophages to taurine chloramine, a long-lived regulator of inflammation. We performed a pooled analysis of all patients who had completed the studies in two six-month NP001 phase 2 trials. Changes in respiratory vital capacity and the muscle mass product, creatinine, defined treated patients who, compared to placebo, had up to a year of extended survival.</p><p><strong>Conclusions: </strong>The observed longer survival in ALS patients with the greatest inflammation-associated muscle loss provides further evidence that ALS is a disease of ongoing innate immune dysfunction and that NP001 is a disease-modifying drug with sustained clinical activity.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11505581/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Biomedicines
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1