In diabetes, abnormal angiogenesis due to hyperglycemia and endothelial dysfunction impairs wound healing and results in high risks of diabetic foot ulcers and mortality. Alternative therapeutic ...methods were attempted to prevent diabetic complications through the activation of endothelial nitric oxide synthase. In this study, direct application of nitric oxide using dinitrosyl iron complexes (DNICs) to promote angiogenesis and wound healing under physiological conditions and in diabetic mice is investigated. Based on in vitro and in vivo studies, DNIC Fe2(μ-SCH2CH2OH)2(NO)4 (DNIC-1) with a sustainable NO-release reactivity (t 1/2 = 27.4 ± 0.5 h at 25 °C and 16.8 ± 1.8 h at 37 °C) activates the NO-sGC-cGMP pathway and displays the best pro-angiogenesis activity overwhelming other NO donors and the vascular endothelial growth factor. Moreover, this pro-angiogenesis effect of DNIC-1 restores the impaired angiogenesis in the ischemic hind limb and accelerates the recovery rate of wound closure in diabetic mice. This study translates synthetic DNIC-1 into a novel therapeutic agent for the treatment of diabetes and highlights its sustainable •NO-release reactivity on the activation of angiogenesis and wound healing.
Generally, the loss rate of human endothelial cells (HCEC) in routine cataract surgery is 8.5%. When the corneal endothelial cells density (ECD) drops, the HCEC may decompensate to keep cornea ...dehydration which leads to corneal edema. Granulomatosis with polyangiitis (GPA) is an uncommon autoimmune disease involving multiple organs including eyes such as conjunctivitis, scleritis, uveitis, and corneal ulcer. In this study, we report two cases of GPA whose corneal ECD decreased significantly after phacoemulsification cataract surgery.
In the first case of 69-year-old male with GPA, the ECD dropped 39.6% (OD) four months after phacoemulsification and 38.1% (OS) six months postoperatively respectively. At the final follow-up, the residual ECD was only 55% in the right eye in the 49
month, and 56% remained in the left eye in the 39
month. In the second case of 54-year old female, left ECD dropped 63.9% at the 4
month after surgery and 69.6% ECD remained at the 15
month postoperatively while similar ECD of right eye before and after left eye surgery.
Extensive preoperative ophthalmic evaluation and meticulous postoperative inflammation control should be applied to prevent severe loss of HCEC in GPA patients.
Abstract
Traumatic brain injury (TBI) triggers inflammatory response and glial scarring, thus substantially hindering brain tissue repair. This process is exacerbated by the accumulation of activated ...immunocytes at the injury site, which contributes to scar formation and impedes tissue repair. In this study, a mussel‐inspired nitric oxide‐release microreservoir (MINOR) that combines the features of reactive oxygen species (ROS) scavengers and sustained NO release to promote angiogenesis and neurogenesis is developed for TBI therapy. The injectable MINOR fabricated using a microfluidic device exhibits excellent monodispersity and gel‐like self‐healing properties, thus allowing the maintenance of its structural integrity and functionality upon injection. Furthermore, polydopamine in the MINOR enhances cell adhesion, significantly reduces ROS levels, and suppresses inflammation. Moreover, a nitric oxide (NO) donor embedded into the MINOR enables the sustained release of NO, thus facilitating angiogenesis and mitigating inflammatory responses. By harnessing these synergistic effects, the biocompatible MINOR demonstrates remarkable efficacy in enhancing recovery in mice. These findings benefit future therapeutic interventions for patients with TBI.
Regarding dihydrogen as a clean and renewable energy source, ammonia borane (NH3BH3, AB) was considered as a chemical H2-storage and H2-delivery material due to its high storage capacity of ...dihydrogen (19.6 wt %) and stability at room temperature. To advance the development of efficient and recyclable catalysts for hydrolytic dehydrogenation of AB with parallel insight into the reaction mechanism, herein, ZIF-67-derived fcc-Co@porous carbon nano/microparticles (cZIF-67_nm/cZIF-67_μm) were explored to promote catalytic dehydrogenation of AB and generation of H2(g). According to kinetic and computational studies, zero-order dependence on the concentration of AB, first-order dependence on the concentration of cZIF-67_nm (or cZIF-67_μm), and a kinetic isotope effect value of 2.45 (or 2.64) for H2O/D2O identify the Co-catalyzed cleavage of the H–OH bond, instead of the H–BH2NH3 bond, as the rate-determining step in the hydrolytic dehydrogenation of AB. Despite the absent evolution of H2(g) in the reaction of cZIF-67 and AB in the organic solvents (i.e., THF or CH3OH) or in the reaction of cZIF-67 and water, Co-mediated activation of AB and formation of a Co-H intermediate were evidenced by theoretical calculation, infrared spectroscopy in combination with an isotope-labeling experiment, and reactivity study toward CO2-to-formate/H2O-to-H2 conversion. Moreover, the computational study discovers a synergistic interaction between AB and the water cluster (H2O)9 on fcc-Co, which shifts the splitting of water into an exergonic process and lowers the thermodynamic barrier for the generation and desorption of H2(g) from the Co-H intermediates. With the kinetic and mechanistic study of ZIF-67-derived Co@porous carbon for catalytic hydrolysis of AB, the spatiotemporal control on the generation of H2(g) for the treatment of inflammatory diseases will be further investigated in the near future.
We investigated the prognostic utility of preoperative neck lymph node-to-primary tumor maximum standardized uptake value ratios (NTRs) in oral cavity squamous cell carcinoma (OSCC). We ...retrospectively reviewed the medical records of 141 consecutive patients who were diagnosed as having OSCC and had received fluorodeoxyglucose-positron emission tomography within 2 weeks prior to radical surgery between 2009 and 2018. To determine the optimal NTR cutoff, receiver operating characteristic analysis for overall survival (OS) was executed. The NTR's prognostic value for disease-free survival (DFS) and OS were determined through Cox proportional hazards analysis and the Kaplan-Meier method. We determined the median (range) follow-up duration to be 35.2 (2.1-122.4) months. The optimal NTR cutoff was 0.273, and patients with a higher NTR (≥0.273) exhibited significantly worse DFS and OS (
= 0.010 and 0.003, respectively). A higher NTR (≥0.273) predicted poorer DFS (hazard ratio: 2.696,
= 0.008) and OS (hazard ratio: 4.865,
= 0.003) in multivariable analysis. We created a nomogram on the basis of the NTR, and it could accurately predict OS (concordance index: 0.774). Preoperative NTRs may be a useful prognostic biomarker for DFS and OS in patients with OSCC who have undergone surgery. NTR-based nomograms may also be helpful prognostic tools in clinical trials.
Abstract We probed the associations of preoperative modified geriatric nutritional risk index (mGNRI) values with prognosis in patients receiving surgery for oral cavity squamous cell carcinoma ...(OCSCC). This retrospective study analyzed the clinical data of 333 patients with OCSCC and undergoing surgery between 2008 and 2017. The preoperative mGNRI was calculated using the following formula: (14.89/C-reactive protein level) + 41.7 × (actual body weight/ideal body weight). We executed receiver operating characteristic curve analyses to derive the optimal mGNRI cutoff and employed Kaplan–Meier survival curves and Cox proportional hazard model to probe the associations of the mGNRI with overall survival (OS) and disease-free survival (DFS). The optimal mGNRI cutoff was derived to be 73.3. We noted the 5-year OS and DFS rates to be significantly higher in the high-mGNRI group than in the low-mGNRI group (both p < 0.001). A preoperative mGNRI below 73.3 was independently associated with unfavorable DFS and OS. A mGNRI-based nomogram was constructed to provide accurate OS predictions (concordance index, 0.781). Hence, preoperative mGNRI is a valuable and cost-effective prognostic biomarker in patients with OCSCC. Our nomogram facilitates the practical use of mGNRI and offers individualized predictions of OS.
Acute epiglottitis (AE) is a potential emergency of the respiratory tract caused mainly by bacterial infection. However, nonbacterial infection causes, such as corrosive injuries, may result in death ...due to gastrointestinal perforation if a timely diagnosis is not available. We report the case of an elderly patient with an acute melancholic episode who encountered corrosive epiglottitis (CE) caused by accidental ingestion of hydrochloric acid and compare the features of CE and AE, including the immediate onset of symptoms, normal findings on blood tests, and endoscopy revealing pale swollen epiglottitis. This case can prove to be an important reference for clinicians for differential diagnosis, especially when treating epiglottitis in patients with psychiatric disorders and unclear expression.
Continued efforts are made on the development of earth-abundant metal catalysts for dehydrogenation/hydrolysis of amine boranes. In this study, complex ...K-18-crown-6-ether(NO)2Fe(μ-MePyr)(μ-CO)Fe(NO)2 (3-K-crown, MePyr = 3-methylpyrazolate) was explored as a pre-catalyst for the dehydrogenation of dimethylamine borane (DMAB). Upon evolution of H2(g) from DMAB triggered by 3-K-crown, parallel conversion of 3-K-crown into (NO)2Fe(N,N′-MePyrBH2NMe2)− (5) and an iron-hydride intermediate (NO)2(CO)Fe(μ-H)Fe(CO)(NO)2− (A) was evidenced by X-ray diffraction/nuclear magnetic resonance/infrared/nuclear resonance vibrational spectroscopy experiments and supported by density functional theory calculations. Subsequent transformation of A into complex (NO)2Fe(μ-CO)2Fe(NO)2− (6) is synchronized with the deactivated generation of H2(g). Through reaction of complex Na-18-crown-6-ether(NO)2Fe(η2-BH4) (4-Na-crown) with CO(g) as an alternative synthetic route, isolated intermediate Na-18-crown-6-ether(NO)2(CO)Fe(μ-H)Fe(CO)(NO)2 (A-Na-crown) featuring catalytic reactivity toward dehydrogenation of DMAB supports a substrate-gated transformation of a pre-catalyst (NO)2Fe(μ-MePyr)(μ-CO)Fe(NO)2− (3) into the iron-hydride species A as an intermediate during the generation of H2(g).
Despite a comprehensive study on the biosynthesis and function of nitric oxide, biological metabolism of nitric oxide, especially when its concentration exceeds the cytotoxic level, remains elusive. ...Oxidation of nitric oxide by O
in aqueous solution has been known to yield NO
. On the other hand, a biomimetic study on the metal-mediated conversion of NO to NO
/NO
via O
reactivity disclosed a conceivable pathway for aerobic metabolism of NO. During the NO-to-NO
conversion, transient formation of metal-bound peroxynitrite and subsequent release of
NO
via O-O bond cleavage were evidenced by nitration of tyrosine residue or 2,4-di-
-butylphenol (DTBP). However, the synthetic/catalytic/enzymatic cycle for conversion of nitric oxide into a nitrite pool is not reported. In this study, sequential reaction of the ferrous complex (PMDTA)Fe(κ
-
,
'-NO
)(κ
-
-NO
) (
; PMDTA = pentamethyldiethylenetriamine) with NO
, KC
, and O
established a synthetic cycle, complex
→ {Fe(NO)
}
DNIC (PMDTA)Fe(NO)
NO
(
) → {Fe(NO)
}
DNIC (PMDTA)Fe(NO)
(
) → (PMDTA)(NO)Fe(κ
-
,
-ONOO) (
) → complex
, for the transformation of nitric oxide into nitrite. In contrast to the reported reactivity of metal-bound peroxynitrite toward nitration of DTBP, peroxynitrite-bound MNIC
lacks phenol nitration reactivity toward DTBP. Presumably, the (PMDTA)Fe core in {Fe(NO)}
MNIC
provides a mononuclear template for intramolecular interaction between Fe-bound peroxynitrite and Fe-bound NO
, yielding Fe-bound nitrite stabilized in the form of complex
. This (PMDTA)Fe-core-mediated concerted peroxynitrite homolytic O-O bond cleavage and combination of the O atom with Fe-bound NO
reveals a novel and effective pathway for NO-to-NO
transformation. Regarding the reported assembly of the dinitrosyliron unit (DNIU) Fe(NO)
in the biological system, this synthetic cycle highlights DNIU as a potential intermediate for nitric oxide monooxygenation activity in a nonheme iron system.
We aimed to determine the timing of neodymium:yttrium-aluminum-garnet (Nd:YAG) laser capsulotomy on corrected-distance visual acuity (CDVA), intraocular pressure (IOP), and spherical equivalent (SE) ...in patients with posterior capsular opacification (PCO). There were 59 patients with unilateral PCO and a history of Nd:YAG laser capsulotomy enrolled and further divided into the early Nd:YAG group (timing < 12 months,
= 25) and late Nd:YAG group (timing > 12 months,
= 34) depending on the elapsed months from phacoemulsification to Nd:YAG laser capsulotomy. The primary outcomes were CDVA, IOP, and SE before (immediately before Nd:YAG laser capsulotomy) and after (weeks one and four after the laser treatment). The independent t test was applied to analyze the difference in CDVA, IOP, and SE between the two groups, while the generalized estimating equation with Bonferroni adjustment was conducted to evaluate the effect of all the parameters on the change in SE with adjusted odds ratio (aOR) and 95% confidence interval (CI). The CDVA showed significant improvement in both the early Nd:YAG group (
= 0.005) and the late Nd:YAG group (
= 0.001), and hyperopic change occurred in both the early Nd:YAG group (
= 0.003) and the late Nd:YAG group (
= 0.017). The early Nd:YAG group revealed more significant hyperopic change compared with the late Nd:YAG group four weeks after Nd:YAG treatment (
< 0.001), which was still significant after multivariable analysis (aOR: 0.899, 95% CI: 0.868-0.930,
= 0.011). In addition, a deeper ACD (aOR: 0.764, 95% CI: 0.671-0.869,
= 0.019) was significantly correlated with hyperopic change. In conclusion, Nd:YAG laser capsulotomy performed within one year after cataract surgery may lead to significant hyperopic change, in which the ACD alteration affects the hyperopic shift significantly.
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