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Green tea's secret weapon: a review on the protective effects of epigallocatechin-3-gallate against ischemia/reperfusion damage. 绿茶的秘密武器:表没食子儿茶素-3-没食子酸酯对缺血/再灌注损伤的保护作用综述。
IF 3.8 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2025-09-05 DOI: 10.1007/s43440-025-00781-y
Yingxin Wang, Ying Cao, Yue Zhao
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引用次数: 0
Involvement of TRPV1 and MOR-NMDAR complex on the antiallodynic effect of LMH-2, a sigma-1 receptor antagonist, in mouse model of diabetic neuropathy - a behavioral approach. 在糖尿病神经病变小鼠模型中,TRPV1和MOR-NMDAR复合物参与sigma-1受体拮抗剂LMH-2的抗异动作用-一种行为方法。
IF 3.6 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2025-08-01 Epub Date: 2025-04-23 DOI: 10.1007/s43440-025-00727-4
Rosa Ventura-Martínez, Guadalupe Esther Ángeles-López, Tania Domínguez-Páez, Gabriel Navarrete-Vázquez, Wendy Arratia-Damián, Maria Eva González-Trujano, Myrna Déciga-Campos

Background: Recently, the antinociceptive effect of LMH-2, a σ1 receptor antagonist, has been reported in diabetic mice with neuropathic pain. However, the mechanism by which this effect is produced is not completely clear. In this study, we explored the involvement of TRPV1 and the MOR-NMDAR complex in the antiallodynic effect of LMH-2 in hyperglycemic mice with neuropathic pain.

Methods: Hyperglycemia was induced in mice by administering streptozotocin-nicotinamide. Four weeks later, once neuropathic pain was established, the antiallodynic effect of LMH-2 (56.2 mg/kg) was evaluated using the up-down method with the von Frey filaments, both in the absence and the presence of capsazepine (8 mg/kg, ip), naloxone (NLX, 1 mg/kg, ip), NMDA (0.4 nM/10 µL, it), or their co-administration (NLX-NMDA). Gabapentin was used as positive control.

Results: Pretreatment with NLX did not alter the antiallodynic effect of LMH-2 in the up-down method with the von Frey filaments in hyperglycemic mice, whereas NMDA significantly reduced it. The addition of NLX to NMDA (NLX-NMDA) did not modify the effect of NMDA alone on the antiallodynic activity of LMH-2. Additionally, capsazepine completely blocked the antinociceptive effect of LMH-2 in hyperglycemic mice. Molecular docking analysis suggested a potential interaction between LMH-2 and TRPV1. Moreover, a higher dose of LMH-2 did not cause mortality or damage in healthy mice.

Conclusion: These results suggest the potential utility of LMH-2 in the treatment of diabetic neuropathy and highlight a key role for TRPV1 in LMH-2's antiallodynic mechanism, along with a possible, albeit limited, interaction with the MOR/NMDA complex.

背景:近年来,有研究报道了一种σ1受体拮抗剂LMH-2对糖尿病小鼠神经性疼痛的抑制作用。然而,产生这种效应的机制尚不完全清楚。在本研究中,我们探讨了TRPV1和MOR-NMDAR复合物在LMH-2对神经性疼痛高血糖小鼠的抗异动作用中的作用。方法:用链脲佐菌素-烟酰胺诱导小鼠高血糖。四周后,一旦确定神经性疼痛,采用von Frey纤维上下法评估LMH-2 (56.2 mg/kg)的抗allodyan作用,无论是否存在辣椒平(8 mg/kg, ip)、纳洛酮(NLX, 1 mg/kg, ip)、NMDA (0.4 nM/10µL, it)或它们的联合给药(NLX-NMDA)。加巴喷丁为阳性对照。结果:NLX预处理对高血糖小鼠上下移法中LMH-2抗异动作用无影响,而NMDA显著降低其抗异动作用。在NMDA中加入NLX (NLX-NMDA)并没有改变NMDA单独对LMH-2抗异动活性的影响。此外,辣椒平完全阻断了LMH-2在高血糖小鼠中的抗伤害感受作用。分子对接分析提示LMH-2与TRPV1可能存在相互作用。此外,高剂量的LMH-2不会导致健康小鼠死亡或损伤。结论:这些结果提示了LMH-2在糖尿病神经病变治疗中的潜在效用,并强调了TRPV1在LMH-2的抗异动机制中的关键作用,以及与MOR/NMDA复合物可能(尽管有限)的相互作用。
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引用次数: 0
Empiric and targeted antibiotic therapy for bloodstream infections in internal medicine patients in Poland: a three-year analysis in a single centre using the AWaRe classification. 波兰内科患者血液感染的经验性和靶向抗生素治疗:使用AWaRe分类在单一中心进行的三年分析。
IF 3.6 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2025-08-01 Epub Date: 2025-06-19 DOI: 10.1007/s43440-025-00753-2
Piotr Piekiełko, Dariusz A Hareza, Ewa Stawowczyk, Estera Jachowicz-Matczak, Jadwiga Wójkowska-Mach

Background: Bloodstream infection (BSI), defined as bacteraemia accompanied by sepsis or septic shock, is a frequent cause of hospitalization in departments of internal medicine (DIM). This study aimed to characterize the epidemiology, microbiological profile, and antibiotic treatment patterns of BSIs in a DIM setting in 2021-2023 in Polish hospital.

Methods: A three-year, single-centre retrospective analysis was conducted at a DIM in Southern Poland. Medical records from 2021 to 2023 were reviewed for patients diagnosed with sepsis (ICD-10 codes A40-A41) with microbiological confirmation. Antibiotic use was assessed using Days of Therapy (DOT) and Length of Therapy (LOT). Empiric and targeted therapies were classified according to the WHO AWaRe (Access, Watch, Reserve) framework.

Results: A total of 124 BSI cases were identified, with an incidence rate of 5.8%. Community-acquired BSIs accounted for 84.3% of cases, while 15.7% were hospital-acquired. The predominant pathogens were Escherichia coli and Staphylococcus aureus. The median LOT for empiric therapy was 3 days (IQR 2-4), with third-generation cephalosporins being the most frequently used agents (78 patients; 43.3%, 228 DOTs; 43.9%). Targeted therapy had a median LOT of 8 days (IQR 5-10), most commonly involving penicillins (33 patients; 28.4%, 291 DOTs; 34.5%). Access group antibiotics were significantly more prevalent in targeted therapy compared to empiric therapy (p < 0.001).

Conclusions: Microbiological confirmation of BSI facilitates a safe de-escalation from broad-spectrum empiric antibiotics to narrow-spectrum targeted therapy, supporting antimicrobial stewardship in internal medicine settings.

背景:血流感染(BSI)被定义为伴随脓毒症或脓毒性休克的菌血症,是内科住院(DIM)的常见原因。本研究旨在描述2021-2023年波兰医院DIM环境中bsi的流行病学、微生物学特征和抗生素治疗模式。方法:在波兰南部的一家DIM进行了为期三年的单中心回顾性分析。回顾了2021年至2023年诊断为败血症(ICD-10代码A40-A41)并经微生物学证实的患者的医疗记录。使用治疗天数(DOT)和治疗时间(LOT)评估抗生素使用情况。根据世卫组织AWaRe(获取、观察、储备)框架对经验性治疗和靶向治疗进行分类。结果:共发现BSI病例124例,发病率5.8%。社区获得性脑损伤占84.3%,15.7%为医院获得性脑损伤。主要病原菌为大肠杆菌和金黄色葡萄球菌。经验性治疗的中位LOT为3天(IQR 2-4),第三代头孢菌素是最常用的药物(78例;43.3%, 228个DOTs;43.9%)。靶向治疗的LOT中位数为8天(IQR 5-10),最常见的是青霉素类药物(33例;29.4%, 291个DOTs;34.5%)。与经验性治疗相比,可及组抗生素在靶向治疗中明显更普遍(p结论:BSI的微生物学确认有助于从广谱经验性抗生素安全降格到窄谱靶向治疗,支持内科环境中的抗菌药物管理。
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引用次数: 0
Unveiling hidden risks: pharmacogenetic insights from a cross-sectional study of statin therapy in the Indian population. 揭示隐藏的风险:药物遗传学的见解从横断面研究他汀类药物治疗在印度人口。
IF 3.6 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2025-08-01 Epub Date: 2025-06-09 DOI: 10.1007/s43440-025-00746-1
Shaik Mohammad Naushad, Palani Kumar Palanichamy, Jagadeesh Babu Sreemanthula, Yadam Reddy Kanaka Durga Devi, Palakonda Gopi, Tajamul Hussain, Vijay Kumar Kutala

Background: Statin usage has increased significantly in India due to the very high incidence of dyslipidemia, however, approximately 18% of the population is at risk for statin-induced myopathy. Hence, we conducted a population-level screening for pharmacogenetic determinants of statin therapy, particularly Solute Carrier Organic Anion Transporter Family Member 1B1 (SLCO1B1) and ATP-binding cassette sub-family G member 2 (ABCG2).

Materials and methods: Whole exome sequencing was performed in 2180 subjects, and the variant data were segregated further into diplotypes and phenotypes.

Results: SLCO1B1 normal function was observed in 81% of subjects (diplotypes: 1/*1, *1/*14, *1/*20, *1/*37, and *37/*37). Increased SLCO1B1 function was observed in 8% of the population (diplotypes: *14/*14 and *20/*20). Decreased function of SLCO1B1 (*1/*15) was observed in 5% of the population. Poor function of SLCO1B1 was observed in 6% of the population (diplotypes: *5/*5 and *15/*15). About 81.46% of subjects displayed normal ABCG2 function, while 17.34% had decreased and 1.19% had poor function. Combined SLCO1B1/ABCG2 functional defects were observed in 7.4% of subjects. Two rare SLCO1B1 variants in SLCO1B1 i.e., rs201722521 and rs71581988, were reported to affect the binding affinity of certain statins. The SLCO1B1 C-C-C-A-A-A haplotype was associated with a 2.22-fold risk for hyperbilirubinemia (95% CI: 1.13-4.36, p = 0.02). Rosuvastatin's daily dose of up to 10 mg is well tolerated across the different SLCO1B1 functionality groups.

Conclusions: This study demonstrates that 11% of our population exhibit decreased or poor function of SLCO1B1 and 7.4% exhibit decreased or poor function of both SLCO1B1 and ABCG2, necessitating adjustments in daily statin doses to minimize the risk for statin-induced myopathy.

背景:由于血脂异常的高发生率,他汀类药物的使用在印度显著增加,然而,大约18%的人口处于他汀类药物诱发的肌病的风险中。因此,我们对他汀类药物治疗的药理学决定因素进行了人群水平的筛选,特别是溶质载体有机阴离子转运蛋白家族成员1B1 (SLCO1B1)和atp结合盒亚家族G成员2 (ABCG2)。材料和方法:对2180名受试者进行全外显子组测序,并将变异数据进一步分离为二倍型和表型。结果:81%的受试者SLCO1B1功能正常(双倍型:1/*1、*1/*14、*1/*20、*1/*37、*37/*37)。在8%的人群中观察到SLCO1B1功能增加(双倍型:*14/*14和*20/*20)。在5%的人群中观察到SLCO1B1功能下降(*1/*15)。SLCO1B1功能低下的人群占6%(双倍型:*5/*5和*15/*15)。81.46%的受试者ABCG2功能正常,17.34%的受试者ABCG2功能下降,1.19%的受试者ABCG2功能差。7.4%的受试者存在SLCO1B1/ABCG2复合功能缺陷。据报道,SLCO1B1中两个罕见的SLCO1B1变异rs201722521和rs71581988会影响某些他汀类药物的结合亲和力。SLCO1B1 c - c - c - a - a单倍型与高胆红素血症的2.22倍风险相关(95% CI: 1.13-4.36, p = 0.02)。瑞舒伐他汀每日剂量高达10mg在不同的SLCO1B1功能组中具有良好的耐受性。结论:该研究表明,11%的人群表现出SLCO1B1功能下降或较差,7.4%的人群表现出SLCO1B1和ABCG2功能下降或较差,需要调整每日他汀类药物剂量,以尽量减少他汀类药物引起的肌病的风险。
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引用次数: 0
Residence time in drug discovery: current insights and future perspectives. 药物发现中的停留时间:当前的见解和未来的展望。
IF 3.6 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2025-08-01 Epub Date: 2025-06-09 DOI: 10.1007/s43440-025-00748-z
Szymon K Kordylewski, Ryszard Bugno, Sabina Podlewska

The temporal stability of ligand-receptor complexes is increasingly acknowledged as a critical factor in drug discovery, influencing both efficacy and pharmacodynamics. Although the relationship between the duration of compound action and complex stability can be traced back to Paul Ehrlich's 19th-century doctrine Corpora non agunt nisi fixata, its significance has gained renewed attention in recent years. This review comprehensively examines the concept of residence time (RT). We first summarize key ligand binding models (lock-and-key, induced-fit, and conformational selection) and delve into various perspectives on how RT impacts functional outcomes. Furthermore, we discuss experimental methods for measuring RT, highlighting both radioligand and non-radioligand approaches. The growing interest in RT has spurred advancements in computational techniques, particularly molecular dynamics simulations, which utilize diverse strategies to observe dissociation events. We outline these molecular dynamics-based methods, their theoretical foundations, and provide examples of their application in assessing RT. Finally, we highlight molecular determinants of prolonged RT, focusing primarily on G protein-coupled receptors (GPCRs) while also incorporating relevant data from other receptor classes.

配体-受体复合物的时间稳定性越来越被认为是药物发现的一个关键因素,影响药效和药效学。虽然复合作用持续时间和复合稳定性之间的关系可以追溯到保罗·埃利希(Paul Ehrlich) 19世纪的学说“非固定体”(Corpora nonagunt nisfixata),但其重要性近年来得到了重新关注。本文综述了停留时间(RT)的概念。我们首先总结了关键配体结合模型(锁-键、诱导拟合和构象选择),并深入探讨了RT如何影响功能结果的各种观点。此外,我们讨论了测量RT的实验方法,重点介绍了辐射配体和非辐射配体方法。对RT的日益增长的兴趣刺激了计算技术的进步,特别是分子动力学模拟,它利用不同的策略来观察解离事件。我们概述了这些基于分子动力学的方法及其理论基础,并提供了它们在评估RT中的应用实例。最后,我们强调了延长RT的分子决定因素,主要关注G蛋白偶联受体(gpcr),同时也结合了其他受体类别的相关数据。
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引用次数: 0
Adolescent cannabidiol treatment produces antidepressant-like effects without compromising long-term cognition in rats. 青少年大麻二酚治疗产生类似抗抑郁的效果,而不损害大鼠的长期认知能力。
IF 3.6 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2025-08-01 Epub Date: 2025-06-16 DOI: 10.1007/s43440-025-00750-5
Laura Gálvez-Melero, Itziar Beruete-Fresnillo, Sandra Ledesma-Corvi, M Julia García-Fuster

Background: Recent preclinical studies have shown sex-dependent antidepressant-like responses of cannabidiol in adolescence, which were dependent on biological sex, early-life stress, and dose. In particular, cannabidiol (10 mg/kg) induced acute and sustained antidepressant-like responses in adolescent male rats, while it lacked efficacy in females. This follow-up study aimed at further characterizing cannabidiol's effects in adolescence, in an attempt to overcome female unresponsiveness, while also evaluating its long-term safety profile in adulthood.

Methods: Groups of adolescent rats of both sexes were treated (ip) with cannabidiol (10, 30, 60 mg/kg) or vehicle (1 ml/kg) for 7 days. Acute (30 min post-injection) and repeated (24 h post-treatment) antidepressant-like responses were measured in the forced-swim test. Brains were collected to evaluate several neurochemical correlates in the hippocampus (CBR1, CBR2, BDNF, and cell proliferation) after adolescent cannabidiol exposure (acute and repeated). Some rats were left undisturbed until adulthood, when long-term effects on cognition were measured in the Barnes maze (short- and long-term memory) or affective-like responses in the forced-swim test. Data was analyzed with two-way ANOVAs (independent variables: sex and treatment).

Results: While the dose of 10 mg/kg of cannabidiol induced antidepressant-like effects in adolescent rats, higher doses had no effect in adolescent rats of both sexes. No changes were observed in any of the hippocampal neuroplasticity markers evaluated. Adolescent cannabidiol exposure did not induce long-term changes in cognitive performance or affective-like behavior.

Conclusions: Overall, our data suggest that adolescent cannabidiol treatment produces dose-dependent antidepressant-like effects of moderate magnitude without compromising long-term cognition in rats.

背景:最近的临床前研究表明,大麻二酚在青春期的抗抑郁样反应依赖于生理性别、早期生活压力和剂量。特别是,大麻二酚(10 mg/kg)在青春期雄性大鼠中诱导急性和持续的抗抑郁样反应,而在雌性大鼠中缺乏疗效。这项后续研究旨在进一步表征大麻二酚在青春期的作用,试图克服女性的无反应性,同时评估其在成年期的长期安全性。方法:将青春期大鼠分为两组,分别给予大麻二酚(10、30、60 mg/kg)或对照(1 ml/kg)治疗7 d。在强迫游泳试验中测量急性(注射后30分钟)和重复(治疗后24小时)抗抑郁样反应。在青少年大麻二酚暴露(急性和重复)后,收集大脑以评估海马中的几种神经化学相关物质(CBR1, CBR2, BDNF和细胞增殖)。一些大鼠不受干扰,直到成年,在巴恩斯迷宫(短期和长期记忆)中测量对认知的长期影响,或在强迫游泳测试中测量情感反应。数据采用双因素方差分析(自变量:性别和治疗)。结果:10 mg/kg剂量的大麻二酚对青春期大鼠有类似抗抑郁的作用,而更高剂量的大麻二酚对雌雄大鼠均无作用。未观察到海马神经可塑性指标的任何变化。青少年接触大麻二酚不会引起认知表现或情感行为的长期变化。结论:总的来说,我们的数据表明,青少年大麻二酚治疗在不影响大鼠长期认知的情况下产生中等程度的剂量依赖性抗抑郁样作用。
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引用次数: 0
Naltrexone dose-selectively modulates goal-directed behavior and the hypothalamic proteome in rats. 纳曲酮剂量选择性调节大鼠目标定向行为和下丘脑蛋白质组。
IF 3.6 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2025-08-01 Epub Date: 2025-05-28 DOI: 10.1007/s43440-025-00735-4
Natalia Malikowska-Racia, Przemysław Mielczarek, Piotr Popik

Background: Naltrexone is an opioid receptor antagonist that can modulate reward processing in opposite directions depending on the dose. Whether naltrexone similarly affects motivation remains unexplored. This study investigates the effects of naltrexone on behavioral measures of motivation and search for potential mechanisms, including the endogenous opioid pathway dependent on proopiomelanocortin (POMC).

Methods: Male Sprague Dawley rats received naltrexone (0.01, 0.1, or 1 mg/kg, ip) for two weeks. During this period, rats were tested daily using a progressive ratio schedule of reinforcement (PR) test and effort-based choice (EBC) that address motivational vigor, directedness, and effort-based decision-making. After tests, the hypothalami were collected for proteomic analysis using data-independent acquisition (DIA).

Results: Low-dose naltrexone (0.01 mg/kg; LDN) transiently increased PR response vigor without altering decision-making in EBC. At 0.1 mg/kg, but not at the high dose of 1 mg/kg, it impaired effort-based decision-making and goal-directedness. Proteomic analysis correlated LDN with the downregulation of a growth hormone (GH) pathway and altered G protein-coupled receptors (GPCR) signaling. Naltrexone's intermediate dose predominantly impacted proteins involved in neural growth, while the 1 mg/kg dose affected proteins related to gene regulation.

Conclusions: Different doses of naltrexone had varying effects on motivational measures and the rat's hypothalamic proteome. Naltrexone 0.1 mg/kg impaired motivational directedness and effort-based decision-making that corresponds to reduced reward signaling due to opioid blockade. In contrast, LDN enhanced vigor, but only early in the treatment. Naltrexone had no effects on the POMC-dependent endogenous opioid pathway, suggesting that a different mechanism underlies its motivational effects.

背景:纳曲酮是一种阿片受体拮抗剂,可以根据剂量调节相反方向的奖励加工。纳曲酮是否也会对动机产生类似的影响尚不清楚。本研究探讨了纳曲酮对动机行为测量的影响,并寻找潜在的机制,包括依赖于propropiomanocortin (POMC)的内源性阿片途径。方法:雄性sd大鼠给予纳曲酮(0.01、0.1、1 mg/kg, ig)治疗2周。在此期间,每天对大鼠进行递进比例强化(PR)测试和基于努力的选择(EBC)测试,以解决动机活力、方向性和基于努力的决策。测试后,收集下丘脑进行蛋白质组学分析,使用数据独立采集(DIA)。结果:低剂量纳曲酮(0.01 mg/kg;LDN在不改变EBC决策的情况下短暂地增加了PR反应活力。当剂量为0.1 mg/kg时,而不是高剂量为1 mg/kg时,它会损害基于努力的决策和目标导向。蛋白质组学分析将LDN与生长激素(GH)通路下调和G蛋白偶联受体(GPCR)信号通路改变相关。纳曲酮的中剂量主要影响与神经生长有关的蛋白质,而1mg /kg剂量影响与基因调控有关的蛋白质。结论:不同剂量纳曲酮对大鼠的动机测量和下丘脑蛋白质组有不同的影响。纳曲酮0.1 mg/kg会损害动机方向性和基于努力的决策,这与阿片类药物阻断导致的奖励信号减少相对应。相比之下,LDN增强活力,但仅在治疗早期。纳曲酮对pomc依赖性内源性阿片通路没有影响,表明其动机作用背后有不同的机制。
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引用次数: 0
Combined effects of HCRTR1/2 gene variants and non-genetic factors on sleep-wake transition and hemodynamic stability during propofol, dexmedetomidine, and remifentanil anesthesia. HCRTR1/2基因变异和非遗传因素对异丙酚、右美托咪定和瑞芬太尼麻醉时睡眠-觉醒转换和血流动力学稳定性的联合影响
IF 3.6 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2025-08-01 Epub Date: 2025-05-29 DOI: 10.1007/s43440-025-00740-7
Zhuoling Zheng, Faling Xue, Haini Wang, Qingling Gu, Rong Hu, Xiaoyan Li, Min Huang, Wenqi Huang, Zhongxing Wang, Jiali Li

Background: Propofol-remifentanil-dexmedetomidine-based total intravenous anesthesia is widely utilized in clinical practice. However, maintaining safety during the sleep-wake transition and ensuring hemodynamic stability continues to pose significant challenges. This study aimed to investigate the impact of genes that are expressed specifically in orexinergic neurons on interindividual variability in the time to loss of consciousness (LOC), time to wake, and cardiovascular fluctuations.

Methods: A total of 250 patients were included in the study. Gene polymorphisms were detected using the Agena Bioscience MassARRAY system. Anesthesia induction began with propofol and was maintained with propofol and remifentanil. Dexmedetomidine was administered before anesthesia induction. The time to LOC, time to wake, heart rate (HR), and mean arterial pressure (MAP) were documented.

Results: HCRTR2 (Hypocretin receptor 2) rs2292040 and rs76380807 were significantly associated with the time to LOC, and HCRTR2 rs7774031 was correlated with the time to wake. HCRTR2 rs3122162, rs3122169, and rs74296544 were correlated with HR fluctuations, and HCRTR1 (Hypocretin receptor 1) rs2176807, rs2271933, rs871634, and HCRTR2 rs74296544 were associated with MAP fluctuations. Multiple linear regression analysis revealed that the Target-controlled infusion (TCI) plasma concentration (Cp) of propofol > 4 µg ml- 1 at the time of LOC and dexmedetomidine were influencing factors for the time to LOC, whereas HCRTR2 rs7774031 influenced the time to wake. Baseline HR, baseline MAP, dexmedetomidine, HCRTR2 rs3122162, and HCRTR1 rs2176807 were predictive factors for cardiovascular susceptibility. The predictive models for the time to LOC, time to wake, mean HR, and mean MAP fluctuations accounted for 41.89%, 3.36%, 35.56%, and 47.41% of variations, respectively.

Conclusions: Genetic variants of HCRTR1 and HCRTR2 may affect sleep-wake transition and hemodynamic stability during propofol, dexmedetomidine, and remifentanil anesthesia.

背景:异丙酚-瑞芬太尼-右美托咪定为基础的全静脉麻醉在临床中应用广泛。然而,维持睡眠-觉醒转换期间的安全性和确保血流动力学稳定性仍然构成重大挑战。本研究旨在探讨在食欲能神经元中特异性表达的基因对意识丧失时间(LOC)、苏醒时间和心血管波动等个体间变异的影响。方法:共纳入250例患者。基因多态性检测采用Agena Bioscience MassARRAY系统。麻醉诱导以异丙酚开始,并以异丙酚和瑞芬太尼维持。麻醉诱导前给予右美托咪定。记录LOC时间、苏醒时间、心率(HR)和平均动脉压(MAP)。结果:HCRTR2(下丘脑分泌素受体2)rs2292040和rs76380807与LOC时间显著相关,HCRTR2 rs7774031与醒来时间显著相关。HCRTR2 rs3122162、rs3122169和rs74296544与HR波动相关,HCRTR1(下丘脑分泌素受体1)rs2176807、rs2271933、rs871634和HCRTR2 rs74296544与MAP波动相关。多元线性回归分析显示,LOC时异丙酚> 4µg ml- 1的靶控输注(TCI)血浆浓度(Cp)和右美托咪定是LOC时间的影响因素,而HCRTR2 rs7774031影响苏醒时间。基线HR、基线MAP、右美托咪定、HCRTR2 rs3122162和HCRTR1 rs2176807是心血管易感性的预测因素。LOC时间、wake - up时间、平均HR和平均MAP波动的预测模型分别占变化的41.89%、3.36%、35.56%和47.41%。结论:HCRTR1和HCRTR2基因变异可能影响异丙酚、右美托咪定和瑞芬太尼麻醉时的睡眠-觉醒转换和血流动力学稳定性。
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引用次数: 0
Inflammatory lung diseases: a clinical and scientific review of the latest advances and challenges. 炎症性肺病:最新进展和挑战的临床和科学回顾。
IF 3.6 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2025-08-01 Epub Date: 2025-06-13 DOI: 10.1007/s43440-025-00749-y
Ahmed A Katamesh, Khaled Almansour, Shimaa M Hassoun, Ossama M Sayed, Mohammed Khaled Bin Break, Randa Mohammed Zaki, Obaid Afzal, Amr Radwan

Inflammatory lung diseases, including chronic obstructive pulmonary disease (COPD), asthma, pulmonary sarcoidosis, and interstitial lung diseases (ILDs), represent a significant cause of morbidity and mortality globally. These conditions are characterized by chronic inflammation and tissue damage, leading to substantial respiratory compromise and impairing quality of life. This review aims to provide a comprehensive overview of pathogenesis, clinical features, and diagnostic approaches for inflammatory lung diseases, emphasizing their shared and distinct characteristics. The review synthesizes current literature on the genetic predisposition, environmental exposures, and immune responses involved in the development and progression of inflammatory lung diseases. It also examines the classification and staging of these conditions to highlight the importance of accurate diagnosis and effective management. Key findings include the complex interplay of numerous factors that contribute to disease development and progression, as well as an analysis of classification and staging systems that support clinical practice. By elucidating the underlying mechanisms and clinical features of inflammatory lung diseases, this review aims to inform the development of novel therapeutic strategies and enhance patient outcomes.

炎性肺病,包括慢性阻塞性肺病(COPD)、哮喘、肺结节病和间质性肺病(ILDs),是全球发病率和死亡率的一个重要原因。这些疾病的特点是慢性炎症和组织损伤,导致严重的呼吸系统损害和生活质量下降。本文综述了肺部炎症性疾病的发病机制、临床特点和诊断方法,强调了它们的共同特点和各自的特点。这篇综述综合了目前关于炎症性肺部疾病发生和发展的遗传易感性、环境暴露和免疫反应的文献。它还检查了这些条件的分类和分期,以强调准确诊断和有效管理的重要性。主要发现包括导致疾病发展和进展的众多因素的复杂相互作用,以及支持临床实践的分类和分期系统的分析。通过阐明炎症性肺部疾病的潜在机制和临床特征,本综述旨在为开发新的治疗策略和提高患者预后提供信息。
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引用次数: 0
Emerging role of neural stem/progenitor cell secretome in brain inflammatory response modulation. 神经干/祖细胞分泌组在脑炎症反应调节中的新作用。
IF 3.6 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2025-08-01 Epub Date: 2025-05-19 DOI: 10.1007/s43440-025-00733-6
Krzysztof Łukowicz, Beata Grygier, Agnieszka Basta-Kaim

Adult stem cells residing in the body's tissues are responsible for the regeneration and replacement of old cells by new ones, thanks to their ability to differentiate. Scientific research increasingly focuses on the regeneration processes associated with these cells and the ability to modulate the microenvironment in which they are located. The modulatory effect can occur through direct interactions of stem cells with other cells or through their paracrine activity by releasing biologically active substances. For the nervous system, neural stem/progenitor cells are located in the subgranular zone in the hippocampal dentate gyrus and the subventricular zone around the lateral ventricles. This type of cell, in addition to giving rise to new neurons depending on the physiological state of the body, is also involved in the modulation of the niche in which they are found. This process plays a particular role in inflammation associated with many neurodegenerative diseases, which is connected with increased activity of the immune system cells. In this review article, we wanted to present the biologically active factors found in the neural stem/progenitor cells' secretome, which are key factors that can contribute physiologically to the silencing of inflammatory processes.

由于具有分化能力,存在于人体组织中的成体干细胞负责再生和新细胞替换旧细胞。科学研究越来越关注与这些细胞相关的再生过程以及调节它们所处微环境的能力。这种调节作用可以通过干细胞与其他细胞的直接相互作用或通过释放生物活性物质的旁分泌活性发生。对于神经系统,神经干/祖细胞位于海马齿状回的颗粒下区和侧脑室周围的室下区。这种类型的细胞,除了根据身体的生理状态产生新的神经元外,还参与调节它们所在的生态位。这个过程在与许多神经退行性疾病相关的炎症中起着特殊的作用,这与免疫系统细胞活性的增加有关。在这篇综述文章中,我们希望介绍在神经干/祖细胞分泌组中发现的生物活性因子,这些因子是生理上有助于炎症过程沉默的关键因素。
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引用次数: 0
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Pharmacological Reports
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