Nitric oxide : biology and chemistry最新文献

{"title":"Application of hydrogen sulfide donor conjugates in different diseases","authors":"Rui Zhang,&nbsp;Wumei Shi,&nbsp;Xiaoyan Wu,&nbsp;Qingfeng Yu,&nbsp;Ying Xiao","doi":"10.1016/j.niox.2024.11.008","DOIUrl":"10.1016/j.niox.2024.11.008","url":null,"abstract":"<div><div>As an endogenous gas signaling molecule, hydrogen sulfide (H₂S) has been proved to have a variety of biological activities. Studies have shown that in some disease state H₂S concentration in the body is lower than normal state. Based on these findings, exogenous H₂S supplementation is expected to be an effective treatment for many diseases. In recent years, a lot of H₂S-releasing substances, namely H₂S donors, have emerged as H₂S sources. Specifically, various H₂S donors also could be connected to drugs or compounds to form H₂S donor conjugates. Many studies have found that H₂S donor conjugates can not only retain the activity of the parent drug, but also reduce the adverse effects of the parent drug, this makes H₂S donor conjugates to be a new kind of drug candidates. In this article, H₂S donor conjugates will be reviewed and classified according to different diseases, such as inflammation, cardiovascular and cerebrovascular diseases, diseases of central nervous system and cancer. This review aims to provide an idea for researchers for further study of H₂S and H₂S donor conjugates.</div></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"154 ","pages":"Pages 128-139"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hydrogen sulfide alleviates endothelial glycocalyx damage and promotes placental angiogenesis in rats exposed to cigarette smoke","authors":"Kexin Zhang ,&nbsp;Geng Wu ,&nbsp;Yonglan Chen ,&nbsp;Qunying Hu ,&nbsp;Yuanyuan Li ,&nbsp;Xinyue Jiang ,&nbsp;Chunfu Gu ,&nbsp;Na Zhang ,&nbsp;Fusheng Zhao","doi":"10.1016/j.niox.2024.12.002","DOIUrl":"10.1016/j.niox.2024.12.002","url":null,"abstract":"<div><div>Our previous study has shown that hydrogen sulfide (H₂S) can attenuate cigarette smoke exposure (CSE)-induced placental injury in rats. This study investigated whether H₂S alleviates CSE-induced endothelial glycocalyx (eGC) impairment and promotes placental angiogenesis in rats. Twenty-four pregnant rats were randomly divided into four groups: control, NaHS (a donor of H₂S), CSE, and CSE + NaHS. On gestational day 21, rat placentas were collected to detect H₂S levels and protein expression of the H₂S-synthesizing enzymes, cystathionine beta synthase (CBS), cystathionine gamma-lyase (CGL), and 3-mercaptopyruvate sulfurtransferase (3-MST), using a C-7Az fluorescent probe, H₂S testing kit, and western blotting, respectively. Transmission electron microscopy and double immunofluorescence staining were performed to observe the placental eGC alterations. Placental angiogenesis, vascular endothelial proliferation and apoptosis, and protein expression levels of the PI3K/AKT/mTOR signaling pathway were assessed in rat placentas. The results showed that the administration of NaHS markedly attenuated the reduction in H₂S levels and the decrease in CBS, CGL, and 3-MST expression caused by CSE in rat placentas. Notably, NaHS treatment distinctly alleviated eGC damage and facilitated placental angiogenesis in CSE-treated rats. NaHS administration effectively promoted placental vascular endothelial proliferation and suppressed endothelial apoptosis in CSE-treated rats. Furthermore, NaHS treatment markedly elevated the phosphorylation of PI3K, AKT, and mTOR in the placenta of CSE-treated rats. Taken together, these results indicate that exogenous administration of H₂S can alleviate CSE-induced eGC damage and promote placental angiogenesis in CSE-treated rats, suggesting that H₂S may be a novel therapeutic agent for the treatment of CSE-associated vascular disease.</div></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"154 ","pages":"Pages 115-127"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"S-Denitrosylation counteracts local inflammation and improves survival in mice infected with K. pneumoniae","authors":"Filipe Rodolfo Moreira Borges Oliveira ,&nbsp;Thiele Osvaldt Rosales ,&nbsp;Daiane Mara Bobermin,&nbsp;Marina Delgobo,&nbsp;Alfeu Zanotto-Filho,&nbsp;Regina Sordi,&nbsp;Jamil Assreuy","doi":"10.1016/j.niox.2024.12.001","DOIUrl":"10.1016/j.niox.2024.12.001","url":null,"abstract":"<div><h3>Aim</h3><div>Sepsis and septic shock remain are significant causes of mortality in the world. The inflammatory response should be at the basis of all organ dysfunction such as cardiovascular dysfunction, characterized by severe hypotension refractory to volume replacement and vasoconstrictor therapy. Nitric oxide (NO) has been implicated as a key element in both inflammatory and cardiovascular components of sepsis. In addition to activating soluble guanylate cyclase and potassium channels, NO also modifies proteins post-translationally by reacting with protein thiol groups, yielding S-nitrosothiols (RS-NO), which can act as endogenous NO reservoirs. Besides its use in quantifying free sulfhydryl groups of proteins and non-protein thiols, DTNB [5,5′-dithiobis-(2-nitrobenzoic acid)] has also been used as a pharmacological tool due to its specificity for oxidizing reactive sulfhydryl groups. Here we aimed to investigate the effects of DTNB in the inflammatory aspects of a sepsis model and to verify whether its effects can be attributed to S-denitrosylation.</div></div><div><h3>Methods</h3><div>Anesthetized female Swiss mice were intratracheally injected with 1 × 10⁸ CFU of <em>K. pneumoniae</em>. Twelve hours after pneumonia-induced sepsis, the animals were injected with vehicle (sodium bicarbonate 5 %, s.c.) or DTNB (31.5, 63 and 126 μmol/kg, s.c.). Twenty-four hours post-sepsis induction, plasma, bronchoalveolar lavage (BAL), and lung tissues were collected for assays (protein, cell count, nitrite + nitrate levels (NOx), cytokine levels, and sulfhydryl groups). In addition, lung S-nitrosylated proteins were visualized by a modified tissue assay for S-nitrosothiols.</div></div><div><h3>Results</h3><div>Sepsis induced a significant vascular leakage in the lungs and elevated NOx levels in BAL, both reduced by DTNB. BAL leukocytosis and elevated IL-1β induced by sepsis were also reduced by DTNB, whereas it did not affect bacterial dissemination to liver, heart and BAL. Sepsis reduced free sulfhydryl groups in BAL and lung and DTNB did not change it. On the other hand, DTNB substantially reduced protein S-nitrosylation levels in the lung parenchyma and halved sepsis-induced mortality in septic mice.</div></div><div><h3>Conclusion</h3><div>Our results show that the administration of DTNB 12 h after bacterial instillation reduced most of the local inflammatory parameters and, more importantly, decreased mortality. These beneficial effects may be due to S-denitrosylation of RS-NO pools carried out by DTNB. Since DTNB was effective in reducing the inflammatory process after its onset, this mechanism of action could serve as a valuable proof of concept for compounds that can be useful to interfere with sepsis outcome.</div></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"154 ","pages":"Pages 105-114"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142795063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of mGlu2 or mGlu5 receptor activators on the production of l-arginine derivatives and the expression of PRMT5 or DDAH1 enzymes in animal models of cognitive decline","authors":"Agata Płoska ,&nbsp;Adrianna Radulska ,&nbsp;Anna Siekierzycka ,&nbsp;Paulina Cieślik ,&nbsp;Michał Santocki ,&nbsp;Iwona T. Dobrucki ,&nbsp;Leszek Kalinowski ,&nbsp;Joanna M. Wierońska","doi":"10.1016/j.niox.2024.11.010","DOIUrl":"10.1016/j.niox.2024.11.010","url":null,"abstract":"<div><div><span>l</span>-arginine derivatives (ADMA, SDMA, NMMA) are endogenous inhibitors of nitric oxide (NO֗) production, which is essential in critical brain processes including blood-brain barrier (BBB) integrity and long-term potentiation (LTP). ADMA and NMMA are degraded by dimethylarginine dimethylaminohydrolase 1 (DDAH1) and protein arginine methyltransferase 5 (PRMT5) is an emerging epigenetic enzyme that mainly represses transcription of target genes via symmetric dimethylation of arginine residues. There is no data concerning the impact of metabotropic glutamate receptors (mGlu) ligands on this aspect of brain physiology.</div><div>In the present studies the impact of positive allosteric modulators (PAM) of mGlu5 (CDPPB) and mGlu2 (LY487379) receptors on <span>l</span>-arginine derivatives, DDAH1 and PRMT5 expression in mouse models of cognitive dysfunction induced with MK-801(0.3 mg/kg) or scopolamine (1 mg/kg), was investigated. Experiments were performed both after acute and chronic (14 days) administration of the compounds, which were administered at the doses 0.1–5 mg/kg (CDBBB) and 0.1–1 mg/kg (LY487379).</div><div>The chronic administration of both compounds normalized the level of <span>l</span>-arginine derivatives in MK-801 model (in brain and plasma) and only low dose of CDPPB prevented scopolamine-induced changes. The expression of DDAH1 and PRMT5 was modulated by CDPPB and LY487379, both in MK-801 and scopolamine models.</div><div>In the novel object recognition (NOR) test low doses of the compounds, inactive after single administration, prevented cognitive decline after chronic injections.</div><div>Our findings highlight the potential of mGlu receptor modulators in treating schizophrenia and possibly dementia by normalizing <span>l</span>-arginine derivatives production, preventing from nitric oxide synthases uncoupling.</div></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"154 ","pages":"Pages 140-151"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142786297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"KLF4's role in regulating nitric oxide production and promoting microvascular formation following ischemic stroke","authors":"Kuo Li,&nbsp;Chuansuo Zhang,&nbsp;Li xuan Wang,&nbsp;Xiaoxuan Wang,&nbsp;Ruyue Wang","doi":"10.1016/j.niox.2024.11.004","DOIUrl":"10.1016/j.niox.2024.11.004","url":null,"abstract":"<div><div>This study examines KLF4's role in endothelial cells (ECs), emphasizing its effects on nitric oxide (NO) production, microvascular formation, and oxidative stress regulation following ischemic stroke. Through high-throughput sequencing, we identified eight cell subpopulations in carotid artery tissues post-stroke, with KLF4 notably elevated in ECs. KLF4 overexpression in ECs promoted NO synthesis, enhanced endothelial tube formation, mitigated oxidative stress, and improved smooth muscle cells (SMCs) function, collectively boosting blood flow in ischemic regions. These findings highlight KLF4 as pivotal in vascular regeneration and oxidative stress reduction, positioning it as a promising target for cardiovascular and cerebrovascular therapies.</div></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"154 ","pages":"Pages 86-104"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The antimicrobial effects of nitric oxide: A narrative review","authors":"Mohamed Okda ,&nbsp;Stefano Spina ,&nbsp;Bijan Safaee Fakhr ,&nbsp;Ryan W. Carroll","doi":"10.1016/j.niox.2025.01.001","DOIUrl":"10.1016/j.niox.2025.01.001","url":null,"abstract":"<div><div>Nitric oxide (NO) is a versatile endogenous molecule with multiple physiological roles, including neurotransmission, vasodilation, and immune regulation. As part of the immune response, NO exerts antimicrobial effects by producing reactive nitrogen species (RNS). These RNS combat pathogens via mechanisms such as DNA deamination, S-nitrosylation of thiol groups, and lipid peroxidation, leading to disruptions in microbial cell membranes and vital protein functions. Due to these broad actions, NO targets many pathogens, including bacteria, fungi, and viruses, with minimal risk of resistance development. Given its potent antimicrobial properties, the therapeutic potential of exogenous NO has been recently studied. Various preparations, such as NO donors, inhaled gaseous NO, and topical preparations, have shown promising results in preclinical and clinical settings. This literature review examines the antimicrobial effects of exogenous NO reported in <em>in vitro</em> studies, animal models, and human clinical trials. We provide an overview of the mechanisms by which NO exerts its antimicrobial activity, highlighting its efficacy against diverse pathogens. By presenting the current findings, we aim to contribute to the growing body of evidence supporting the use of NO as a versatile antimicrobial agent in clinical practice.</div></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"155 ","pages":"Pages 20-40"},"PeriodicalIF":3.2,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142966124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microvessels-on-chip: Exploring endothelial cells and COVID-19 plasma interaction with nitric oxide metabolites","authors":"Kanchana Pandian ,&nbsp;Rudmer Postma ,&nbsp;Anton Jan van Zonneveld ,&nbsp;Amy Harms ,&nbsp;Thomas Hankemeier","doi":"10.1016/j.niox.2025.01.002","DOIUrl":"10.1016/j.niox.2025.01.002","url":null,"abstract":"<div><div>COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), primarily manifests as a flu-like illness with lung injury, often necessitating supplemental oxygen. Elderly individuals and those with pre-existing cardiovascular diseases are at increased risk of mortality. The endothelial barrier disruption observed in patients indicates systemic viral invasion and widespread endotheliitis. Endothelial dysfunction, characterized by impaired nitric oxide (NO) production, contributes to vasoconstriction, inflammation, and coagulation abnormalities seen in COVID-19. In this study, we investigated the impact of COVID-19 patient-derived plasma on the endothelium through NO metabolite analysis using an in vitro 3D micro vessel model. Our experiments revealed alterations in NO metabolites in response to COVID-19 patient plasma perfusion, with BH4+BH2 supplementation improving citrulline levels in severe COVID-19 patient models. Positive correlation between arginase activity and eNOS activity was observed in the severe COVID-19 patient model but not in the mild COVID-19 patient model. These findings underscore the importance of endothelial dysfunction in COVID-19 pathogenesis and highlight potential therapeutic targets for mitigating vascular complications associated with severe infection.</div></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"155 ","pages":"Pages 12-19"},"PeriodicalIF":3.2,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142951955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of ciliary length on the mechanical response of osteocytes to fluid shear stress","authors":"Dong Ding ,&nbsp;Ran Tian ,&nbsp;Xiao Yang ,&nbsp;Zhe Ren ,&nbsp;Zhi-Cheng Jing ,&nbsp;Xin-Tong Wu ,&nbsp;Lian-Wen Sun","doi":"10.1016/j.niox.2024.12.003","DOIUrl":"10.1016/j.niox.2024.12.003","url":null,"abstract":"<div><h3>Background</h3><div>Osteocytes are crucial for detecting mechanical stimuli and translating them into biochemical responses within the bone. The primary cilium, a cellular 'antenna,' plays a vital role in this process. However, there is a lack of direct correlation between cilium length changes and osteocyte mechanosensitivity changes. This study aims to reveal the relationship between ciliary length and nitric oxide (NO) release in osteocytes to show how primary cilia may be involved in reducing osteocyte mechanosensitivity caused by microgravity.</div></div><div><h3>Materials and methods</h3><div>We used the MLO-Y4 cell line and primary osteoblasts to adjust the ciliary length using chloral hydrate (CH) for shortening and lithium ions (Li⁺) for elongation. We then examined the impact of varied ciliary lengths on osteocyte response to fluid shear stress, focusing on the PC1/PC2–Ca²⁺-NO signaling pathway. Co-culture systems assessed downstream effects on osteoblast function, including collagen secretion and mineralization.</div></div><div><h3>Results</h3><div>We observed a significant correlation between ciliary length and osteocyte mechanosensitivity, with longer primary cilia enhancing Ca²⁺ influx and NO release in response to fluid shear stress. However, contrary to expectations, calmodulin (CaM) expression did not increase with ciliary length, suggesting alternative pathways, such as PKC or Akt/PKB, may modulate <em>p</em>-eNOS activity. Co-cultured osteoblasts showed altered osteogenic functions regulated by osteocyte-derived signals influenced by primary cilia length.</div></div><div><h3>Conclusion</h3><div>Our findings clarify the role of primary cilia length in modulating osteocyte mechanosensitivity and their influence on osteoblast function, highlighting a complex regulatory network that may not solely rely on CaM for NO release. These insights contribute to a deeper understanding of bone mechanotransduction and could have implications for developing therapeutic targets for osteocyte-related disorders.</div></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"155 ","pages":"Pages 1-11"},"PeriodicalIF":3.2,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142903238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The relationship of nitric oxide synthase 3(NOS3) gene polymorphism in the risk of pulmonary arterial hypertension: A systematic review and meta-analysis","authors":"Kang Yi ,&nbsp;Tao Guo ,&nbsp;Wen-Xin Wang ,&nbsp;Shao-E He ,&nbsp;Xin Zhang ,&nbsp;Jian-Guo Xu ,&nbsp;Zi-Qiang Wang ,&nbsp;Fan-Ning Wang ,&nbsp;Tao You","doi":"10.1016/j.niox.2024.11.009","DOIUrl":"10.1016/j.niox.2024.11.009","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;We performed the present study to better elucidate the correlation of nitric oxide synthase 3 (NOS3) gene polymorphism with the risk of pulmonary arterial hypertension (PAH).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Material/methods&lt;/h3&gt;&lt;div&gt;According to the designed search strategy, a systematic literature search was performed through the PubMed, Embase, Web of Science, Cochrane Library, CNKI, VIP and Wan Fang databases to collect published case-control studies on the correlation between NOS3 gene polymorphism and PAH. The search deadline was December 26, 2023. Two reviewers independently screened the literature, extracted data and evaluated the quality according to the inclusion and exclusion criteria. Meta-analysis was performed using RevMan 5.4 software. The odds ratio (OR) and 95 % confidence interval (CI) of the genotype distribution were used as the effect indicators.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;A total of 11 eligible studies were included, involving three single nucleotide polymorphism (SNP) sites of the NOS3 gene: G894T (rs1799983), 4b/4a (rs61722009), and T-786C (rs2070744). The meta-analysis revealed that for PAH analysis, 4 genetic models of NOS3 G894T polymorphism increased the risk of PAH: the allele model (T vs G, OR = 1.9, 95%CI [1.16, 3.11],P = 0.01), the homozygote model (GG vs TT, OR = 1.91, 95%CI [1.04, 3.51], P = 0.04), the heterozygote model (GG vs GT, OR = 3.19, 95%CI [1.65, 6.19], P = 0.0006) and the dominant model (GT + TT vs GG, OR = 3.06, 95%CI [1.54, 6.09], P = 0.001). In the subgroups analysis, the NOS3 G894T polymorphism was found to be associated with the risk of PAH subgroups, including CHD combined with PAH and COPD combined with PAH, Particularly, there is a highly significant correlation with CHD combined with PAH. 2 genetic models of NOS3 4b/4a polymorphism increased the risk of PAH: the homozygote model (BB vs AA, OR = 2.1, 95%CI [1.02, 4.35], P = 0.04) and the recessive model (BB + BA vs AA, OR = 2.55, 95%CI [1.27, 5.11], P = 0.009). In the subgroups analysis, the NOS3 4b/4a polymorphism was found to be associated with the susceptibility of CHD combined with PAH. The results of the combined analysis of each gene model of NOS3 T-786C gene polymorphism sites were not statistically significant, and their P values were all&gt;0.05. The NOS3 G894T and NOS3 4b/4a gene polymorphism had been found to be associated with the risk of PAH in different regional and racial subgroups. In contrast to the NOS3 G894T gene polymorphism, which increased the risk of PAH development in the yellow race subgroup, the NOS3 4b/4a gene polymorphism reduced the risk of PAH development in the white race subgroup and was a protective factor.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;The NOS3 G894T (rs1799983) and NOS3 4b/4a (rs61722009) gene polymorphism have a strong correlation with the risk of PAH, with this association varying among different regions and ethnicities. However, it is still necessary to expand the sample ","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"154 ","pages":"Pages 51-76"},"PeriodicalIF":3.2,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Critical role of hydrogen sulfide in the management of neurodegenerative disease","authors":"Rajashree Pawar ,&nbsp;Dheeraj Pandey ,&nbsp;Saba Naqvi ,&nbsp;Abha Sharma","doi":"10.1016/j.niox.2024.11.006","DOIUrl":"10.1016/j.niox.2024.11.006","url":null,"abstract":"<div><div>Hydrogen sulfide has been known to humans for about 300 years and the previous studies emphasize only on its toxic side effects. In the last two decennium, researchers have varied their perspectives and insights towards H₂S biology based on experimental findings. It has been found that H₂S is an endogenic gaseous signaling molecule in many organisms and plays a crucial role in many systems and diseases. Early reports suggest that H₂S as a neuromodulator influences calcium levels within the brain cells which ultimately control memory, learning, and cognition. It has also been observed that some complications in the pathogenesis of neurodegenerative diseases are due to anomalies in the biosynthesis and metabolism of H₂S. This review focuses on the role of H₂S in the pathophysiology of major neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease and Vascular dementia. H₂S was observed to have a protective role in the above-mentioned neurological conditions and the H₂S donor therapy may help in disease management. The H₂S gas displays a neuroprotective role and protects against cellular damage thereby declining the neurological conditions. Some studies have revealed that treatment with H₂S donors has improved neuronal damage, restored memory and cognition in animal models. In this review, we have discussed the role of H₂S donors as neuroprotective agents with examples of some of the natural and synthetic H₂S donors, and also briefly enumerated the molecules used to detect H₂S in neurodegenerative diseases.</div></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"154 ","pages":"Pages 77-85"},"PeriodicalIF":3.2,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142693321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}