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1.
Asian J Androl ; 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39091129

RESUMO

The genome tagging project (GTP) plays a pivotal role in addressing a critical gap in the understanding of protein functions. Within this framework, we successfully generated a human influenza hemagglutinin-tagged sperm-specific protein 411 (HA-tagged Ssp411) mouse model. This model is instrumental in probing the expression and function of Ssp411. Our research revealed that Ssp411 is expressed in the round spermatids, elongating spermatids, elongated spermatids, and epididymal spermatozoa. The comprehensive examination of the distribution of Ssp411 in these germ cells offers new perspectives on its involvement in spermiogenesis. Nevertheless, rigorous further inquiry is imperative to elucidate the precise mechanistic underpinnings of these functions. Ssp411 is not detectable in metaphase II (MII) oocytes, zygotes, or 2-cell stage embryos, highlighting its intricate role in early embryonic development. These findings not only advance our understanding of the role of Ssp411 in reproductive physiology but also significantly contribute to the overarching goals of the GTP, fostering groundbreaking advancements in the fields of spermiogenesis and reproductive biology.

2.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(7): 695-700, 2024 Jul 15.
Artigo em Chinês | MEDLINE | ID: mdl-39014945

RESUMO

OBJECTIVES: To study the clinical manifestations, laboratory features, and labial gland pathological features in children with systemic lupus erythematosus (SLE) complicated by Sjögren's syndrome (SS). METHODS: A retrospective analysis was conducted on 102 children with SLE who underwent labial gland biopsies at Renji Hospital, Shanghai Jiao Tong University School of Medicine from January 2013 to December 2022. The children were divided into two groups based on the presence of SS: the SLE with SS group (SLE-SS; 60 children) and the SLE-only group (42 children). According to the focus score (FS) of the labial glands, children in the SLE-SS group were further subdivided into FS≥4 subgroup (26 children) and FS<4 subgroup (34 children). The clinical data of the groups were compared. RESULTS: Compared to the SLE-only group, children in the SLE-SS group had less skin and mucosal involvement, were more likely to have positive anti-SSA and anti-SSB antibodies, and had higher levels of rheumatoid factor (P<0.05). There was no significant difference in treatment protocols between the two groups (P>0.05). Compared to the FS<4 subgroup, the FS≥4 subgroup had more frequent musculoskeletal involvement (P<0.05), but there was no significant difference in SLE disease activity or other major organ involvement between the subgroups (P>0.05). CONCLUSIONS: Children with SLE complicated by SS are less likely to have skin and mucous membrane involvement and exhibit specific serological characteristics. The SLE-SS children with an FS≥4 are more likely to experience musculoskeletal involvement. However, FS is not associated with disease activity or other significant organ damage.


Assuntos
Lúpus Eritematoso Sistêmico , Síndrome de Sjogren , Humanos , Síndrome de Sjogren/complicações , Síndrome de Sjogren/patologia , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/patologia , Feminino , Masculino , Criança , Estudos Retrospectivos , Adolescente , Anticorpos Antinucleares/sangue , Pré-Escolar , Fator Reumatoide/sangue , Lábio/patologia
3.
Int J Mol Sci ; 25(13)2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38999932

RESUMO

The World Health Organization (WHO) highlights a greater susceptibility of males to tuberculosis (TB), a vulnerability attributed to sex-specific variations in body fat and dietary factors. Our study delves into the unexplored terrain of how alterations in body fat influence Mycobacterium tuberculosis (Mtb) burden, lung pathology, immune responses, and gene expression, with a focus on sex-specific dynamics. Utilizing a low-dose Mtb-HN878 clinical strain infection model, we employ transgenic FAT-ATTAC mice with modulable body fat to explore the impact of fat loss (via fat ablation) and fat gain (via a medium-fat diet, MFD). Firstly, our investigation unveils that Mtb infection triggers severe pulmonary pathology in males, marked by shifts in metabolic signaling involving heightened lipid hydrolysis and proinflammatory signaling driven by IL-6 and localized pro-inflammatory CD8+ cells. This stands in stark contrast to females on a control regular diet (RD). Secondly, our findings indicate that both fat loss and fat gain in males lead to significantly elevated (1.6-fold (p ≤ 0.01) and 1.7-fold (p ≤ 0.001), respectively) Mtb burden in the lungs compared to females during Mtb infection (where fat loss and gain did not alter Mtb load in the lungs). This upsurge is associated with impaired lung lipid metabolism and intensified mitochondrial oxidative phosphorylation-regulated activity in lung CD8+ cells during Mtb infection. Additionally, our research brings to light that females exhibit a more robust systemic IFNγ (p ≤ 0.001) response than males during Mtb infection. This heightened response may either prevent active disease or contribute to latency in females during Mtb infection. In summary, our comprehensive analysis of the interplay between body fat changes and sex bias in Mtb infection reveals that alterations in body fat critically impact pulmonary pathology in males. Specifically, these changes significantly reduce the levels of pulmonary CD8+ T-cells and increase the Mtb burden in the lungs compared to females. The reduction in CD8+ cells in males is linked to an increase in mitochondrial oxidative phosphorylation and a decrease in TNFα, which are essential for CD8+ cell activation.


Assuntos
Tecido Adiposo , Pulmão , Mycobacterium tuberculosis , Animais , Feminino , Masculino , Camundongos , Pulmão/imunologia , Pulmão/microbiologia , Pulmão/patologia , Pulmão/metabolismo , Tecido Adiposo/metabolismo , Tecido Adiposo/imunologia , Tuberculose Pulmonar/imunologia , Tuberculose Pulmonar/patologia , Tuberculose Pulmonar/microbiologia , Camundongos Transgênicos , Fatores Sexuais , Modelos Animais de Doenças , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Caracteres Sexuais , Camundongos Endogâmicos C57BL
4.
World J Gastrointest Surg ; 16(6): 1926-1932, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38983326

RESUMO

BACKGROUND: The treatment of postoperative anastomotic stenosis after excision of rectal cancer is challenging. Endoscopic balloon dilation and radial incision are not effective in all patients. We present a new endoscopy-assisted magnetic compression technique (MCT) for the treatment of rectal anastomotic stenosis. We successfully applied this MCT to a patient who developed an anastomotic stricture after radical resection of rectal cancer. CASE SUMMARY: A 50-year-old man had undergone laparoscopic radical rectal cancer surgery at a local hospital 5 months ago. A colonoscopy performed 2 months ago indicated that the rectal anastomosis was narrow due to which ileostomy closure could not be performed. The patient came to the Magnetic Surgery Clinic of the First Affiliated Hospital of Xi'an Jiaotong University after learning that we had successfully treated patients with colorectal stenosis using MCT. We performed endoscopy-assisted magnetic compression surgery for rectal stenosis. The magnets were removed 16 d later. A follow-up colonoscopy performed after 4 months showed good anastomotic patency, following which, ileostomy closure surgery was performed. CONCLUSION: MCT is a simple, non-invasive technique for the treatment of anastomotic stricture after radical resection of rectal cancer. The technique can be widely used in clinical settings.

6.
Spectrochim Acta A Mol Biomol Spectrosc ; 322: 124835, 2024 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-39024787

RESUMO

The excited (S1) state charge distribution characteristics and fluorescence mechanism of fluorescence probes benzyl (6-cyano-2-naphthoyl)-L-valinate (NPI) and benzyl (6-amino-2-naphthoyl)-L-valinate (NPA) have been discussed using density functional theory (DFT) and time-dependent density functional theory (TD-DFT). Further analysis by constructing a torsional potential energy curve (PEC) shows that a well-defined minimum energy conformation is observed when the C-C single bond between the valine benzyl ester and naphthalene ring in NPI rotates. For NPA, the most stable conformation is the naphthalene ring conformation with dihedral angle N2C1C2C3 of -30.60°, whose total energy is 0.17 kcal/mol lower than that of the second most stable conformer. The frontier molecular orbitals (FMOs) demonstrate that NPI exhibits a low degree of charge coupling, and the oscillator intensity is close to zero, indicating that it is not conducive to luminescence. However, in the S1 state, the oscillator strength of NPA is 1.2044, which is a bright state, resulting in the strong emitting. Additionally, fluorescence imaging is favored as a visual observation technique, and Stokes shift is an important physical parameter to measure fluorescence. According to the idea that changing the number and position of functional groups can affect the photophysical properties of fluorescent dyes, o-NPDI, p-NPDI and m-NPDI dyes were newly designed and o-NPDA, p-NPDA, m-NPDA produced after recognition of Hg2+. The spectral performance results show that the newly designed fluorescent dye (p-NPDA) can not only emit in the near infrared region after recognizing Hg2+, but also has a large Stokes shift (236 nm). This indirectly reflects that para-substitution is more conducive to Stokes shift, and has become one of the strategies for fluorescent dye design.

7.
Trends Pharmacol Sci ; 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-39003157

RESUMO

PANoptosis is a unique innate immune inflammatory lytic cell death pathway initiated by an innate immune sensor and driven by caspases and RIPKs. As a distinct pathway, the execution of PANoptosis cannot be hindered by targeting other cell death pathways, such as pyroptosis, apoptosis, or necroptosis. Instead, targeting key PANoptosome components can serve as a strategy to prevent this form of cell death. Given the physiological relevance in several diseases, PANoptosis is a pivotal therapeutic target. Notably, previous research has primarily focused on the role of PANoptosis in cancer and infectious and inflammatory diseases. By contrast, its role in cardiovascular diseases has not been comprehensively discussed. Here, we review the available evidence on PANoptosis in cardiovascular diseases, including cardiomyopathy, atherosclerosis, myocardial infarction, myocarditis, and aortic aneurysm and dissection, and explore a variety of agents that target PANoptosis, with the overarching goal of providing a novel complementary approach to combatting cardiovascular diseases.

8.
Front Pharmacol ; 15: 1423684, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39045048

RESUMO

Multidrug resistance is a substantial obstacle in treating non-small cell lung cancer (NSCLC) with therapies like cisplatin (DDP)-based adjuvant chemotherapy and EGFR-tyrosine kinase inhibitors (TKIs). Aaptamine-7 (AP-7), a benzonaphthyridine alkaloid extracted from Aaptos aaptos sponge, has been shown to exhibit a broad spectrum of anti-tumor activity. However, the anti-cancer activity of AP-7 in combination with DDP and its molecular mechanisms in multidrug-resistant NSCLC are not yet clear. Our research indicates that AP-7 bolsters the growth inhibition activity of DDP on multidrug-resistant NSCLC cells. AP-7 notably disrupts DDP-induced cell cycle arrest and amplifies DDP-induced DNA damage effects in these cells. Furthermore, the combination of AP-7 and DDP downregulates Chk1 activation, interrupts the DNA damage repair-dependent Chk1/CDK1 pathway, and helps to overcome drug resistance and boost apoptosis in multidrug-resistant NSCLC cells and a gefitinib-resistant xenograft mice model. In summary, AP-7 appears to enhance DDP-induced DNA damage by impeding the Chk1 signaling pathway in multidrug-resistant NSCLC, thereby augmenting growth inhibition, both in vitro and in vivo. These results indicate the potential use of AP-7 as a DDP sensitizer in the treatment of multidrug-resistant NSCLC.

9.
J Mol Model ; 30(7): 210, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38877350

RESUMO

CONTEXT: To estimate the influence of temperature on properties of 2,4,6,8,10,12-hexanitro- 2,4,6,8,10,12-hexaazaisowurtzitane/1,4-dinitroimidazole (CL-20/1,4-DNI) cocrystal explosive, the supercell crystal of CL-20/1,4-DNI cocrystal model was established. The mechanical properties, sensitivity, and stability of cocrystal model under different temperatures (T = 225 K, 250 K, 275 K, 300 K, 325 K, 350 K) were predicted. Results show that mechanical parameters, including bulk modulus, tensile modulus and shear modulus are the lowest when temperature is 300 K, while Cauchy pressure is the highest, indicating that CL-20/1,4-DNI cocrystal model has better mechanical properties at 300 K. Cohesive energy density (CED) and its components energies decrease monotonically with the increase of temperature, illustrating that the CL-20 and 1,4-DNI molecules are activated and the safety of cocrystal explosive is worsened with the increase of temperature. Cocrystal model has relatively higher binding energy when the temperature is 300 K, implying that the CL-20/1,4-DNI cocrystal explosive is more stable under this condition. METHODS: The CL-20/1,4-DNI cocrystal model was optimized and the properties were predicted through molecular dynamics (MD) method. The MD simulation was performed with COMPASS force field and the ensemble was set as NPT, external pressure was set as 0.0001 GPa.

10.
J Cardiothorac Surg ; 19(1): 344, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38907311

RESUMO

BACKGROUND: In this study we investigated the impact of ABC stroke score on the recurrence of paroxysmal atrial fibrillation (PAF) following radiofrequency catheter ablation (RFCA). METHODS: A total of 132 patients with PAF who underwent RFCA from October 2018 to September 2019 were included in this study. During the first phase of this study the patients were categorized into two groups based on late recurrence of atrial fibrillation after RFCA. In the second phase, the patients were further divided into two groups based on whether their ABC stroke score was ≥ 6.5. RESULT: The univariate analysis indicated that the risk factors for late recurrence of PAF included early recurrence, ABC stroke score, CHA2DS2-VASc score, and NT-proBNP (P < 0.05). Cox multivariate regression analysis revealed that ABC stroke score (P = 0.006) and early recurrence (P = 0.000) were independent predictors of late recurrence, and ABC stroke score ≥ 6.5 was a risk for predicting recurrence of PAF after RFCA with a sensitivity of 66.7% and specificity of 65.7%. After the completion of the 1:1 matching, the univariate Cox analysis indicated that an elevated score of ABC stroke (≥ 6.5) was an independent predictor of late recurrence of PAF (HR = 2.687, 95% CI: 1.036-6.971, P = 0.042). However, using an ABC stroke score cut off at 6.4 predicted the recurrence of atrial tachyarrhythmia with 85% sensitivity and 58.5% specificity. CONCLUSION: An ABC stroke score ≥ 6.4 is a predictor for late recurrence of PAF after RFCA.


Assuntos
Fibrilação Atrial , Ablação por Cateter , Recidiva , Acidente Vascular Cerebral , Humanos , Fibrilação Atrial/cirurgia , Masculino , Feminino , Ablação por Cateter/efeitos adversos , Pessoa de Meia-Idade , Acidente Vascular Cerebral/etiologia , Fatores de Risco , Estudos Retrospectivos , Idoso , Medição de Risco/métodos , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia
11.
World J Gastrointest Surg ; 16(5): 1443-1448, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38817285

RESUMO

BACKGROUND: The treatment of postoperative anastomotic stenosis (AS) after resection of colorectal cancer is challenging. Endoscopic balloon dilation is used to treat stenosis in such cases, but some patients do not show improvement even after multiple balloon dilations. Magnetic compression technique (MCT) has been used for gastrointestinal anastomosis, but its use for the treatment of postoperative AS after colorectal cancer surgery has rarely been reported. CASE SUMMARY: We report a 72-year-old man who underwent radical resection of colorectal cancer and ileostomy one year ago. An ileostomy closure was prepared six months ago, but colonoscopy revealed a narrowing of the rectal anastomosis. Endoscopic balloon dilation was performed three times, but colonoscopy showed no significant improvement in stenosis. The AS was successfully treated using MCT. CONCLUSION: MCT is a minimally invasive method that can be used for the treatment of postoperative AS after colorectal cancer surgery.

12.
Spectrochim Acta A Mol Biomol Spectrosc ; 317: 124391, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-38704998

RESUMO

Eight molecular structures (BT-A1 to BT-A8) with high-performance non-fullerene acceptor (NFA) were selected for organic solar cells (OSCs) and non-linear optical (NLO) applications. Their electronic, photovoltaic (PV) and optoelectronic properties were tuned by adding powerful electron-withdrawing groups to the acceptor (A) of the D-π-A-π-D structure. Using time-dependent density functional theory (TD-DFT) techniques, based on the laws of quantum chemical calculations, the absorption spectra, stability of the highest and lowest-energy molecular orbitals (HOMO/LUMOs), electron density, intramolecular charge transfer (ICT), transition density matrix (TDM), were examined. The binding energy (Eb) and density of states (DOS) were probed to realize the optoelectronic analysis of the structures BT-A1 to BT-A8. Noncovalent interactions (NCIs) based on a reduced density gradient (RDG) were used to describe the nature and strength of D-A interactions in the molecules BT-A1 to BT-A8. The new refined molecules BT-A1 to BT-A8 exhibited strong absorbance bands between 408-721 nm and high electron transfer contribution (ETC) ranges between 87-96 %, along with the smallest excitation energies (Ex) between 1.71-3.55 eV in the solvent dichloromethane. Dipolar moment strengths ranging from 0.38 to 4.72 Debye in both the excited and ground states have determined with good solubility properties of BT-A1 to BT-A8 in polar solvent. Highly effective charge mobilities and prevention of charge recombination have been demonstrated by the electron (0.18-0.41 eV) and hole RE values (0.13-0.89 eV) for the new compounds. Power conversion efficiencies (PCE) of BT-A1 to BT-A8 were nearly the same because of better outcomes compared to the molecules in the BT. Compared to poly[4.8-bis(5-(2-ethylhexyl)thiophen-2-yl)benzo[1,2-b: 4,5-b']dithiophene-2,6- diyl-alt-(4-2-ethylhexyl)-3-fluorothieno[3,4-b]thiophene-)-2-carboxylate-2-6-diyl)] (PTB7-Th), the open circuit voltages (Voc) of compounds BT-A1 to BT-A8 were ranged from 1.52 to 2.13 eV. The polarizability (α) and hyperpolarizability (ß) of the molecules BT-A1 to BT-A8 were used to determine the non-linear optical (NLO) properties. The results showed that BT-A2, BT-A6 and BT-A7 have good NLO activity. This computational analysis demonstrates the superiority of the molecules with NFA. Hence the compounds are advised for the use in production of high-performance OSCs and NLO activity.

13.
J Med Chem ; 67(10): 7836-7858, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38695063

RESUMO

The approval of venetoclax, a B-cell lymphoma-2 (Bcl-2) selective inhibitor, for the treatment of chronic lymphocytic leukemia demonstrated that the antiapoptotic protein Bcl-2 is a druggable target for B-cell malignancies. However, venetoclax's limited potency cannot produce a strong, durable clinical benefit in other Bcl-2-mediated malignancies (e.g., diffuse large B-cell lymphomas) and multiple recurrent Bcl-2 mutations (e.g., G101V) have been reported to mediate resistance to venetoclax after long-term treatment. Herein, we described novel Bcl-2 inhibitors with increased potency for both wild-type (WT) and mutant Bcl-2. Comprehensive structure optimization led to the clinical candidate BGB-11417 (compound 12e, sonrotoclax), which exhibits strong in vitro and in vivo inhibitory activity against both WT Bcl-2 and the G101V mutant, as well as excellent selectivity over Bcl-xL without obvious cytochrome P450 inhibition. Currently, BGB-11417 is undergoing phase II/III clinical assessments as monotherapy and combination treatment.


Assuntos
Antineoplásicos , Mutação , Proteínas Proto-Oncogênicas c-bcl-2 , Proteínas Proto-Oncogênicas c-bcl-2/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Humanos , Animais , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Relação Estrutura-Atividade , Camundongos , Linhagem Celular Tumoral , Sulfonamidas/farmacologia , Sulfonamidas/química , Ratos , Descoberta de Drogas
14.
Circ Res ; 135(1): 93-109, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38770649

RESUMO

BACKGROUND: Hyperproliferation of pulmonary arterial smooth muscle cells (PASMCs) and consequent pulmonary vascular remodeling are the crucial pathological features of pulmonary hypertension (PH). Protein methylation has been shown to be critically involved in PASMC proliferation and PH, but the underlying mechanism remains largely unknown. METHODS: PH animal models were generated by treating mice/rats with chronic hypoxia for 4 weeks. SMYD2-vTg mice (vascular smooth muscle cell-specific suppressor of variegation, enhancer of zeste, trithorax and myeloid Nervy DEAF-1 (deformed epidural auto-regulatory factor-1) domain-containing protein 2 transgenic) or wild-type rats and mice treated with LLY-507 (3-cyano-5-{2-[4-[2-(3-methylindol-1-yl)ethyl]piperazin-1-yl]-phenyl}-N-[(3-pyrrolidin-1-yl)propyl]benzamide) were used to investigate the function of SMYD2 (suppressor of variegation, enhancer of zeste, trithorax and myeloid Nervy DEAF-1 domain-containing protein 2) on PH development in vivo. Primary cultured rat PASMCs with SMYD2 knockdown or overexpression were used to explore the effects of SMYD2 on proliferation and to decipher the underlying mechanism. RESULTS: We demonstrated that the expression of the lysine methyltransferase SMYD2 was upregulated in the smooth muscle cells of pulmonary arteries from patients with PH and hypoxia-exposed rats/mice and in the cytoplasm of hypoxia-induced rat PASMCs. More importantly, targeted inhibition of SMYD2 by LLY-507 significantly attenuated hypoxia-induced pulmonary vascular remodeling and PH development in both male and female rats in vivo and reduced rat PASMC hyperproliferation in vitro. In contrast, SMYD2-vTg mice exhibited more severe PH phenotypes and related pathological changes than nontransgenic mice after 4 weeks of chronic hypoxia treatment. Furthermore, SMYD2 overexpression promoted, while SMYD2 knockdown suppressed, the proliferation of rat PASMCs by affecting the cell cycle checkpoint between S and G2 phases. Mechanistically, we revealed that SMYD2 directly interacted with and monomethylated PPARγ (peroxisome proliferator-activated receptor gamma) to inhibit the nuclear translocation and transcriptional activity of PPARγ, which further promoted mitophagy to facilitate PASMC proliferation and PH development. Furthermore, rosiglitazone, a PPARγ agonist, largely abolished the detrimental effects of SMYD2 overexpression on PASMC proliferation and PH. CONCLUSIONS: Our results demonstrated that SMYD2 monomethylates nonhistone PPARγ and inhibits its nuclear translocation and activation to accelerate PASMC proliferation and PH by triggering mitophagy, indicating that targeting SMYD2 or activating PPARγ are potential strategies for the prevention of PH.


Assuntos
Histona-Lisina N-Metiltransferase , Hipertensão Pulmonar , Hipóxia , Mitofagia , Músculo Liso Vascular , Miócitos de Músculo Liso , PPAR gama , Artéria Pulmonar , Ratos Sprague-Dawley , Animais , Humanos , Masculino , Camundongos , Ratos , Proliferação de Células , Células Cultivadas , Histona-Lisina N-Metiltransferase/metabolismo , Histona-Lisina N-Metiltransferase/genética , Hipertensão Pulmonar/metabolismo , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/patologia , Hipertensão Pulmonar/genética , Hipóxia/complicações , Hipóxia/metabolismo , Metilação , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , PPAR gama/metabolismo , Artéria Pulmonar/patologia , Artéria Pulmonar/metabolismo , Remodelação Vascular
15.
J Asian Nat Prod Res ; : 1-17, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38572941

RESUMO

In recent years, with sinomenine hydrochloride as the main ingredient, Qingfengteng had been formulated as various dosage forms for clinical treatment. Subsequent findings confirmed a variety of biological roles for sinomenine. Here, 15 H2S-donating sinomenine derivatives were synthesized. Target hybrids a11 displayed substantial cytotoxic effects on cancer cell lines, particularly against K562 cells, with an IC50 value of 1.36 µM. In-depth studies demonstrated that a11 arrested cell cycle at G1 phase, induced apoptosis via both morphological changes in nucleus and membrane potential collapse in mitochondria. These results indicated a11 exerted an antiproliferative effect through apoptosis induction via mitochondrial pathway.

16.
Zhongguo Gu Shang ; 37(4): 406-10, 2024 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-38664213

RESUMO

OBJECTIVE: To investigate the efficacy of antibiotic cement column combined with iliac bone graft in the treatment of open fracture with bone defect of distal femur. METHODS: From October 2014 to March 2021, 16 patients of open fracture bone defect of distal femur were treated with antibiotic bone cement column and iliac bone graft, including 12 males and 4 females. The age ranged from 28 to 68 years old. There were 11 cases of traffic accident injury, 5 cases of falling injury, 3 cases as Gustilo type Ⅰ, 5 cases as type Ⅱ and 8 cases as type ⅢA. AO classification was used:9 cases of C2 type and 7 cases of C3 type. The time from injury to final bone grafting ranged from 4 to 119 days. The length of bone defect ranged from 2 to10 cm. Fractures healing time, complications and knee function Merchan score were recorded. RESULTS: All the 16 patients were followed up from 9 to 29 months. The incisions of 16 patients healed in one stage without postoperative infection, plate fracture, limb shortening and valgus and varus deformity. The healing time randed from 4 to 10 months . Knee joint function according to the Merchant scoring standard, showed that 8 cases were excellent, 4 cases were good, 3 cases were fair, and 1 case was poor. CONCLUSION: The use of antibiotic bone cement column combined with iliac bone graft in the treatment of open and complex bone defects of distal femur is an effective surgical method to prevent infection, assist fracture reduction, increase fixation strength and significantly reduce the amount of bone grafting.


Assuntos
Antibacterianos , Cimentos Ósseos , Transplante Ósseo , Fraturas Expostas , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Transplante Ósseo/métodos , Idoso , Fraturas Expostas/cirurgia , Antibacterianos/administração & dosagem , Fêmur/cirurgia , Fraturas do Fêmur/cirurgia
17.
Artigo em Inglês | MEDLINE | ID: mdl-38521483

RESUMO

BACKGROUND: Locking plates are widely used in open reduction internal fixation (ORIF) for proximal humeral fracture (PHF). However, the optimal surgical treatment of unstable, displaced PHF in elderly patients remains controversial. This study aimed to compare the radiological and clinical outcomes of surgical treatment of PHF in the elderly with locking plate (LP) alone and locking plate combined with 3D printed polymethylmethacrylate (PMMA) prosthesis augmentation (LP-PA). METHODS: From May 2015 to April 2021, a total of 97 patients aged ≥ 60 years with acute unstable PHF who underwent osteosynthesis with either LP (46 patients) or LP-PA (51 patients) were retrospectively analyzed. For the LP-PA group, a customized proximal humeral prosthesis made of PMMA cement was intra-operatively fabricated by a three-dimensional (3D) printed prototype mold for the humeral medial support. Radiological outcomes were analyzed by measuring the value of neck-shaft angle (NSA) and humeral head height (HHH). The clinical outcomes were evaluated using Constant-Murley Score (CMS), Disabilities of the Arm Shoulder and Hand (DASH) score, American Shoulder and Elbow Surgeons (ASES) score, and the shoulder range of motion (ROM). Pain was measured using a visual analogue scale (VAS). RESULTS: At the one-year follow-up, all fractures healed radiologically and clinically. The mean changes of NSA and HHH over the follow-up period were markedly smaller in the LP-PA group (3.8 ± 0.9° and 1.7 ± 0.3 mm) than those in the LP group (9.7 ± 2.1° and 3.2 ± 0.6 mm, both P < 0.0001). The LP-PA group also presented lower DASH score (17.1 ± 3.6), higher ASES score (89.5 ± 11.2) and better ROM in forward elevation (142 ± 26°) and external rotation (59 ± 11°) compared to the LP group (28.9 ± 4.8 for DASH score, P < 0.0001; 82.3 ± 9.0 for ASES score, P < 0.001; 129 ± 21° for forward elevation, P = 0.008; and 52 ± 9° for external rotation, P = 0.001). There was no significant difference in overall complication rate between the two groups, although the complication rate of screw perforation was higher in the LP-PA group (P = 0.172). CONCLUSIONS: For PHF in elderly patients, the combination of LP fixation and PMMA prosthesis augmentation effectively improved humeral head support and reduction maintenance, providing satisfactory outcomes both radiologically and clinically. This technique also reduced the incidence of screw perforation associated with plate fixation alone, making it a reasonable option to ensure satisfactory clinical outcomes.

18.
Huan Jing Ke Xue ; 45(2): 1128-1140, 2024 Feb 08.
Artigo em Chinês | MEDLINE | ID: mdl-38471950

RESUMO

To explore the effects of different concentrations of zinc (Zn) on the growth and root architecture classification of maize seedlings under cadmium (Cd) stress, a hydroponic experiment was conducted to study the effects of different concentrations of Zn (0, 10, 25, 50, 100, 200, and 400 µmol·L-1) on the growth, root architecture and classification characteristics, Cd content, root Cd uptake capacity, and photosynthetic system of maize seedlings under Cd stress (50 µmol·L-1) by using Zhengdan 958 as the experimental material. Principal component analysis and the membership function method were used for comprehensive evaluation. The results showed that the 50 µmol·L-1 Cd stress had a significant toxic effect on maize seedlings, which significantly reduced chlorophyll content and photosynthetic parameters. The main root length, plant height, biomass, root forks, and root tips, including the root length and root surface area of the grade Ⅰ-Ⅲ diameter range and the root volume of the grade Ⅰ-Ⅱ diameter range, decreased significantly, which hindered the normal growth and development of maize seedlings. Compared with that under no Zn application, 100 µmol·L-1 and 200 µmol·L-1 Zn application reduced the uptake of Cd by maize seedlings, significantly reduced the Cd content in shoots and roots and the Cd uptake efficiency. The toxic effect on maize seedlings was alleviated, and the fresh weight, dry weight, tolerance index, and root forks of shoots and roots were significantly increased. The photosynthesis of maize seedlings was significantly enhanced, and the photosynthetic rate and the total chlorophyll content was significantly increased. The RL, SA, and RV in the Ⅰ-Ⅱ diameter range reached the maximum at 100 µmol·L-1 Zn, and the RL, SA, and RV in the Ⅲ diameter range reached the maximum at 200 µmol·L-1 Zn, which were significantly higher than those without Zn treatment. The comprehensive evaluation of the growth tolerance of maize seedlings showed that 100 µmol·L-1 and 200 µmol·L-1 Zn had better effects on alleviating Cd toxicity. Comprehensive analysis showed that the application of appropriate concentration of Zn could reduce the Cd content in maize seedlings, the Cd uptake capacity, and Cd uptake efficiency of roots; increase the biomass accumulation of maize seedlings; reduce the effect of Cd toxicity on root architecture; reduce the effect on the light and system; and improve the tolerance of maize seedlings to Cd.


Assuntos
Plântula , Poluentes do Solo , Zinco , Cádmio , Zea mays , Raízes de Plantas , Clorofila
20.
Photochem Photobiol Sci ; 23(3): 575-585, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38386257

RESUMO

Our main focus is to explore the atomic electronegativity-dependent photoinduced behavior of styryl derivatives (HBO, HBS, and HBSe). The results of structural parameter calculation by the DFT method show that the intramolecular hydrogen bonds of normal and tautomer form are strengthened and weakened, respectively, in an excited state (S1), which is conducive to the excited intramolecular proton transfer (ESIPT) process. The enhancement of excited hydrogen bond is beneficial to the ESIPT process from the aspects of infrared vibration frequency (IR), Mulliken's charge analysis, and density gradient reduction (RDG). Additionally, by determining the bond energy with the band critical point (BCP) parameter, we found that the lower the electronegativity of the atom, the larger the hydrogen bond strength at the excited state and the more likely ESIPT reaction occurs. Meanwhile, the intramolecular H-bonds O-H…N in HBO, HBS, and HBSe are enhanced with the weakened electron-withdrawing capacity of the atom (from O to S and Se). Subsequently, frontier molecular orbital (FMOs) and charge density difference (CDD) analyses essentially revealed that electron redistribution induces the ESIPT process. Low atomic electronegativity exhibits the high chemical activity of the excited state. Furthermore, to demonstrate the electronegativity-dependent ESIPT behavior of the system, we built potential energy curves (PECs) and located the transition states (TS) of proton transfer processes.

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