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1.
Sci Rep ; 14(1): 10060, 2024 05 02.
Artículo en Inglés | MEDLINE | ID: mdl-38698246

RESUMEN

This study aimed to evaluate the safety and efficiency of hybrid endoscopic submucosal dissection (H-ESD) using a newly developed ALL IN ONE (AIO) snare. This was a matched control study in a porcine model. Five paired simulated stomach lesions 2-2.5 cm in size were removed by H-ESD using an AIO snare or conventional ESD (C-ESD) using an endoscopic knife. The outcomes of the two procedures were compared, including en-bloc resection rates, procedure times, intraprocedural bleeding volumes, muscular injuries, perforations, thicknesses of the submucosal layer in resected specimens, and stomach defects. All simulated lesions were resected en-bloc. Specimens resected by H-ESD and C-ESD were similar in size (7.68 ± 2.92 vs. 8.42 ± 2.42 cm2; P = 0.676). H-ESD required a significantly shorter procedure time (13.39 ± 3.78 vs. 25.99 ± 4.52 min; P = 0.031) and submucosal dissection time (3.99 ± 1.73 vs. 13.1 ± 4.58 min; P = 0.003) versus C-ESD; H-ESD also yielded a faster dissection speed (241.37 ± 156.84 vs. 68.56 ± 28.53 mm2/min; P = 0.042) and caused fewer intraprocedural bleeding events (0.40 ± 0.55 vs. 3.40 ± 1.95 times/per lesion; P = 0.016) than C-ESD. The thicknesses of the submucosal layer of the resected specimen (1190.98 ± 134.07 vs. 1055.90 ± 151.76 µm; P = 0.174) and the residual submucosal layer of the stomach defect (1607.94 ± 1026.74 vs. 985.98 ± 445.58 µm; P = 0.249) were similar with both procedures. The AIO snare is a safe and effective device for H-ESD and improves the treatment outcomes of gastric lesions by shortening the procedure time.


Asunto(s)
Resección Endoscópica de la Mucosa , Mucosa Gástrica , Animales , Resección Endoscópica de la Mucosa/métodos , Resección Endoscópica de la Mucosa/efectos adversos , Resección Endoscópica de la Mucosa/instrumentación , Porcinos , Mucosa Gástrica/cirugía , Gastroscopía/métodos , Tempo Operativo , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/patología , Estómago/cirugía , Modelos Animales
2.
Org Lett ; 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38696713

RESUMEN

An electrochemical oxidative difunctionalization of diazo compounds with diselenides and nucleophiles has been developed. This innovative approach yields a diverse array of selenium-containing pyrazole esters and alkoxy esters, overcoming the limitations of traditional synthesis methods. Remarkably, various nucleophiles, including acids, alcohols, and pyrazoles, can be seamlessly incorporated. Notably, this protocol boasts high atom efficiency, excellent functional group tolerance, and good efficiency and operates under transition metal- and oxidant-free conditions, distinguishing it in the field.

3.
Front Cardiovasc Med ; 11: 1340687, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38495943

RESUMEN

Objective: The initial operation for type A aortic dissection has limitations, and there may be a need for reoperation in cases such as giant pseudoaneurysm formation and reduced blood supply to the distal vessels. In this study, we collected case data of patients who underwent cardiac major vascular surgery at our hospital to analyze the effectiveness of reoperation treatment options for type A aortic dissection and to summarize our treatment experience. Method: Between June 2018 and December 2022, 62 patients with type A aortic dissection (TAAD) underwent reoperation after previous surgical treatment. Of these, 49 patients (45 males) underwent endovascular aortic repair (EVAR) with a mean age of (49.69 ± 10.21) years (30-75 years), and 13 patients (11 males) underwent thoracoabdominal aortic replacement (TAAR) with a mean age of (41.00 ± 11.18) years (23-66 years). In this study, we retrospectively analyzed the recorded data of 62 patients. In addition, we summarized and analyzed their Computed Tomographic Angiography (CTA) results and perioperative complications. Outcome: In the EVAR group, 47 patients (95.92%) were successfully implanted with overlapping stents, and 2 patients died in the perioperative period. Postoperative complications included cerebral infarction (4.08%), acute renal insufficiency (30.61%), pulmonary insufficiency and need for ventilator (6.12%), poor wound healing (2.04%), postoperative reoperation (16.33%), and lower limb ischemia (2.04%). In the TAAR group, 12 patients (92.31%) were successfully revascularized and 1 patient died in the perioperative period. Postoperative complications included cerebral infarction (7.69%), acute kidney injury (46.15%), pulmonary insufficiency and need for ventilator (15.38%), poor wound healing (30.77%) and postoperative reoperation (15.38%). Conclusion: According to the results of the study, compared with TAAR, EVAR was less invasive, faster recovery, and offered a better choice for some high-risk and high-age patients with comorbid underlying diseases. However, the rate of revascularization was higher after EVAR than TAAR due to vascular lesions. Compared with the use of ascending aortic replacement + hemi-aortic arch replacement for acute type A aortic dissection in many countries and regions, the use of ascending aortic replacement + aortic arch replacement + elephant trunk stent is more traumatic in China, but facilitates reoperation. For young patients, the choice of treatment should be individualized combining vascular lesions and long-term quality of life.

4.
World J Psychiatry ; 14(2): 245-254, 2024 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-38464768

RESUMEN

BACKGROUND: Many studies have explored the relationship between depression and metabolic syndrome (MetS), especially in older people. China has entered an aging society. However, there are still few studies on the elderly in Chinese communities. AIM: To investigate the incidence and risk factors of depression in MetS patients in mainland China and to construct a predictive model. METHODS: Data from four waves of the China Health and Retirement Longitudinal Study were selected, and middle-aged and elderly patients with MetS (n = 2533) were included based on the first wave. According to the center for epidemiological survey-depression scale (CESD), participants with MetS were divided into depression (n = 938) and non-depression groups (n = 1595), and factors related to depression were screened out. Subsequently, the 2-, 4-, and 7-year follow-up data were analyzed, and a prediction model for depression in MetS patients was constructed. RESULTS: The prevalence of depression in middle-aged and elderly patients with MetS was 37.02%. The prevalence of depression at the 2-, 4-, and 7-year follow-up was 29.55%, 34.53%, and 38.15%, respectively. The prediction model, constructed using baseline CESD and Physical Self-Maintenance Scale scores, average sleep duration, number of chronic diseases, age, and weight had a good predictive effect on the risk of depression in MetS patients at the 2-year follow-up (area under the curve = 0.775, 95% confidence interval: 0.750-0.800, P < 0.001), with a sensitivity of 68% and a specificity of 74%. CONCLUSION: The prevalence of depression in middle-aged and elderly patients with MetS has increased over time. The early identification of and intervention for depressive symptoms requires greater attention in MetS patients.

5.
Angew Chem Int Ed Engl ; 63(13): e202317740, 2024 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-38318927

RESUMEN

Plasmon-mediated electrocatalysis that rests on the ability of coupling localized surface plasmon resonance (LSPR) and electrochemical activation, emerges as an intriguing and booming area. However, its development seriously suffers from the entanglement between the photoelectronic and photothermal effects induced by the decay of plasmons, especially under the influence of applied potential. Herein, using LSPR-mediated CO2 reduction on Ag electrocatalyst as a model system, we quantitatively uncover the dominant photoelectronic effect on CO2 reduction reaction over a wide potential window, in contrast to the leading photothermal effect on H2 evolution reaction at relatively negative potentials. The excitation of LSPR selectively enhances the CO faradaic efficiency (17-fold at -0.6 VRHE ) and partial current density (100-fold at -0.6 VRHE ), suppressing the undesired H2 faradaic efficiency. Furthermore, in situ attenuated total reflection-surface enhanced infrared absorption spectroscopy (ATR-SEIRAS) reveals a plasmon-promoted formation of the bridge-bonded CO on Ag surface via a carbonyl-containing C1 intermediate. The present work demonstrates a deep mechanistic understanding of selective regulation of interfacial reactions by coupling plasmons and electrochemistry.

6.
Acta Pharm Sin B ; 14(1): 335-349, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38261838

RESUMEN

Targeting multiple immune mechanisms may overcome therapy resistance and further improve cancer immunotherapy for humans. Here, we describe the application of virus-like vesicles (VLV) for delivery of three immunomodulators alone and in combination, as a promising approach for cancer immunotherapy. VLV vectors were designed to deliver single chain interleukin (IL)-12, short-hairpin RNA (shRNA) targeting programmed death ligand 1 (PD-L1), and a dominant-negative form of IL-17 receptor A (dn-IL17RA) as a single payload or as a combination payload. Intralesional delivery of the VLV vector expressing IL-12 alone, as well as the trivalent vector (designated CARG-2020) eradicated large established tumors. However, only CARG-2020 prevented tumor recurrence and provided long-term survival benefit to the tumor-bearing mice, indicating a benefit of the combined immunomodulation. The abscopal effects of CARG-2020 on the non-injected contralateral tumors, as well as protection from the tumor cell re-challenge, suggest immune-mediated mechanism of protection and establishment of immunological memory. Mechanistically, CARG-2020 potently activates Th1 immune mechanisms and inhibits expression of genes related to T cell exhaustion and cancer-promoting inflammation. The ability of CARG-2020 to prevent tumor recurrence and to provide survival benefit makes it a promising candidate for its development for human cancer immunotherapy.

7.
J Asian Nat Prod Res ; 26(2): 177-188, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38166573

RESUMEN

Two pairs of new dihydrophenanthro[b]furan enantiomers blephebibnols G-H (1-2), one new dihydrophenanthro[b]furan derivative blephebibnol I (3), along with four known analogues (4-7), were isolated from the tubers of Bletilla striata. Their structures including the absolute configurations were determined by the combination of spectroscopic data analysis, ECD and NMR calculations. Compounds 1a, 1b, and 2b showed inhibition of NO production in LPS-stimulated BV-2 cells, with IC50 values ranging from 4.11 to 14.65 µM. Further mechanistic study revealed that 1a suppressed the phosphorylation of p65 subunit to regulate the NF-κB signaling pathway. In addition, some compounds displayed selective cytotoxic activities against HCT-116, HepG2, A549, or HGC27 cancer cell lines with IC50 values ranging from 0.1 to 8.23 µM.


Asunto(s)
Orchidaceae , Transducción de Señal , Estructura Molecular , Espectroscopía de Resonancia Magnética , FN-kappa B , Orchidaceae/química
8.
Small ; 20(7): e2305817, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37814379

RESUMEN

Complete ethanol oxidation reaction (EOR) in C1 pathway with 12 transferred electrons is highly desirable yet challenging in direct ethanol fuel cells. Herein, PtRh jagged nanowires synthesized via a simple wet-chemical approach exhibit exceptional EOR mass activity of 1.63 A mgPt-1 and specific activity of 4.07 mA cm-2 , 3.62-fold and 4.28-folds increments relative to Pt/C, respectively. High proportions of 69.33% and 73.42% of initial activity are also retained after chronoamperometric test (80 000 s) and 1500 consecutive potential cycles, respectively. More importantly, it is found that PtRh jagged nanowires possess superb anti-CO poisoning capability. Combining X-ray absorption spectroscopy, X-ray photoelectron spectroscopy as well as density functional theory calculations unveil that the remarkable catalytic activity and CO tolerance stem from both the Rh-induced electronic effect and geometric effect (manifested by shortened Pt─Pt bond length and shrinkage of lattice constants), which facilitates EOR catalysis in C1 pathway and improves reaction kinetics by reducing energy barriers of rate-determining steps (such as *CO → *COOH). The C1 pathway efficiency of PtRh jagged nanowires is further verified by the high intensity of CO2 relative to CH3 COOH/CH3 CHO in infrared reflection absorption spectroscopy.

9.
Nat Commun ; 14(1): 7934, 2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-38040719

RESUMEN

Arginase, a manganese (Mn)-dependent enzyme, is indispensable for urea generation and ammonia disposal in the liver. The potential role of fructose in Mn and ammonia metabolism is undefined. Here we demonstrate that fructose overconsumption impairs hepatic Mn homeostasis and ammonia disposal in male mice. Fructose overexposure reduces liver Mn content as well as its activity of arginase and Mn-SOD, and impairs the clearance of blood ammonia under liver dysfunction. Mechanistically, fructose activates the Mn exporter Slc30a10 gene transcription in the liver in a ChREBP-dependent manner. Hepatic overexpression of Slc30a10 can mimic the effect of fructose on liver Mn content and ammonia disposal. Hepatocyte-specific deletion of Slc30a10 or ChREBP increases liver Mn contents and arginase activity, and abolishes their responsiveness to fructose. Collectively, our data establish a role of fructose in hepatic Mn and ammonia metabolism through ChREBP/Slc30a10 pathway, and postulate fructose dietary restriction for the prevention and treatment of hyperammonemia.


Asunto(s)
Fructosa , Manganeso , Masculino , Ratones , Animales , Manganeso/toxicidad , Manganeso/metabolismo , Fructosa/metabolismo , Amoníaco/metabolismo , Arginasa/genética , Arginasa/metabolismo , Hígado/metabolismo , Factores de Transcripción/metabolismo , Homeostasis
10.
World J Clin Cases ; 11(33): 8038-8043, 2023 Nov 26.
Artículo en Inglés | MEDLINE | ID: mdl-38075577

RESUMEN

BACKGROUND: Kommerell's diverticulum (KD) with aberrant left subclavian artery is a rare congenital deformity and also has very little research literature about it (35% of case study). There are three types of aortic arch diverticulum. Even literature concerning the treatment options are limited. CASE SUMMARY: We present a case report of a 50-year-old male with KD in the right aortic arch with aberrant left subclavian artery. We conducted a total endovascular repair procedure, which is innovative and will spread more light in the medical world. Our patient has no past medical history and is a non-smoker and non-alcoholic. Patient presented with shortness of breath, chest pain and dizziness for six months. Blood tests were done and computerized tomography (CT) angiogram of the chest confirmed the diagnosis, illustrating showed a 3.9 cm KD. On Day 1, the CT angiogram showed mild dilatation of the thoracic aorta, adjacent esophagus, trachea was compressed and displaced. Surgery was planned as the treatment modality. Carotid-Subclavian artery bypass and endovascular aortic repair was conducted. We used prolene 5-0 C1 sutures to precisely anastomose a 6-mm Dacron graft to the left subclavian artery. Haemostasis was secured and wounds were closed. Protamine was administered and patient was shifted to intensive care unit. Post-operative, patient responded favorably and was discharged. Regular follow-up is done. CONCLUSION: The procedure we performed is novel. This will help the cardio-thoracic surgeons a better insight about the full procedures we conducted, thereby bringing more light and better treatment options in managing KD with aberrant subclavian artery.

12.
Biol Pharm Bull ; 46(10): 1371-1384, 2023 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-37532524

RESUMEN

This study examined the effects of 1,8-cineole on reducing oxidative stress injury and restoring mitochondrial function in oxygen-glucose deprivation and reoxygenation (OGD/R) HT22 cells via the nuclear factor erythrocyte 2 related factor 2 (Nrf2) pathway. The optimal concentration of 1,8-cineole to reduce OGD/R injury was screened via cell morphology, cell survival rate, and lactate dehydrogenase (LDH) leakage rate. Oxidative damage was observed by measuring superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), catalase (CAT) activities, and reactive oxygen species (ROS), glutathione (GSH), protein carbonyl, malondialdehyde (MDA), lipid peroxidation (LPO) content, and 8-hydroxy-2 deoxyguanosine (8-OHDG) expression. Mitochondrial function was observed by mitochondrial membrane potential (MMP) and ATPase activity. Nrf2 pathways were observed by the expression levels of total Nrf2, nucleus Nrf2, reduced nicotinamide adenine dinucleotide phosphate (NAD(P)H): quinone oxidoreductase 1 (NQO1) and heme oxygenase-1 (HO-1), the mRNA levels of HO-1 and NQO1. Among different concentrations of 1,8-cineole for promoting HT22 cell proliferation and attenuated OGD/R injury, 10 µmol/L 1,8-cineole was the best. After 1,8-cineole treatment, SOD, GSH-PX, and CAT activities and GSH content increased, while ROS, MDA, LPO, protein carbonyl, and 8-OHDG levels decreased. 1,8-Cineole could restore MMP and increase mitochondrial enzyme activity. It could also increase the total Nrf2, nucleus Nrf2, NQO1, and HO-1, and Nrf2 inhibitor brusatol reduced the effect of 1,8-cineole. Immunofluorescence assay showed that 1,8-cineole could facilitate the transfer of Nrf2 into the nucleus. 1,8-cineole increased the mRNA levels of NQO1 and HO-1. The above results showed that 1,8-cineole could alleviate OGD/R-induced oxidative damage and restores mitochondrial function by activating the Nrf2 signal pathway.


Asunto(s)
Factor 2 Relacionado con NF-E2 , Oxígeno , Oxígeno/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Eucaliptol/farmacología , Eucaliptol/metabolismo , Glucosa/metabolismo , Transducción de Señal , Estrés Oxidativo , Antioxidantes/farmacología , Glutatión/metabolismo , Superóxido Dismutasa/metabolismo , Mitocondrias/metabolismo , Hemo-Oxigenasa 1/metabolismo
13.
Molecules ; 28(16)2023 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-37630387

RESUMEN

Indoleamine-2,3-dioxygenase 1 (IDO1) and signal transducer and activator of transcription 3 (STAT3) have emerged as significant targets in the tumor microenvironment for cancer therapy. In this study, we synthesized three novel 2-amino-1,4-naphthoquinone amide-oxime derivatives and identified them as dual inhibitors of IDO1 and STAT3. The representative compound NK3 demonstrated effective binding to IDO1 and exhibited good inhibitory activity (hIDO1 IC50 = 0.06 µM), leading to its selection for further investigation. The direct interactions between compound NK3 and IDO1 and STAT3 proteins were confirmed through surface plasmon resonance analysis. A molecular docking study of compound NK3 revealed key interactions between NK3 and IDO1, with the naphthoquinone-oxime moiety coordinating with the heme iron. In the in vitro anticancer assay, compound NK3 displayed potent antitumor activity against selected cancer cell lines and effectively suppressed nuclear translocation of STAT3. Moreover, in vivo assays conducted on CT26 tumor-bearing Balb/c mice and an athymic HepG2 xenograft model revealed that compound NK3 exhibited potent antitumor activity with low toxicity relative to 1-methyl-L-tryptophan (1-MT) and doxorubicin (DOX). Overall, these findings provided evidence that the dual inhibitors of IDO1 and STAT3 may offer a promising avenue for the development of highly effective drug candidates for cancer therapy.


Asunto(s)
Naftoquinonas , Factor de Transcripción STAT3 , Humanos , Animales , Ratones , Simulación del Acoplamiento Molecular , Estudios Prospectivos , Amidas/farmacología , Ratones Endogámicos BALB C , Naftoquinonas/farmacología , Oximas/farmacología
14.
Proc Natl Acad Sci U S A ; 120(24): e2220867120, 2023 06 13.
Artículo en Inglés | MEDLINE | ID: mdl-37279265

RESUMEN

The mammalian cochlear epithelium undergoes substantial remodeling and maturation before the onset of hearing. However, very little is known about the transcriptional network governing cochlear late-stage maturation and particularly the differentiation of its lateral nonsensory region. Here, we establish ZBTB20 as an essential transcription factor required for cochlear terminal differentiation and maturation and hearing. ZBTB20 is abundantly expressed in the developing and mature cochlear nonsensory epithelial cells, with transient expression in immature hair cells and spiral ganglion neurons. Otocyst-specific deletion of Zbtb20 causes profound deafness with reduced endolymph potential in mice. The subtypes of cochlear epithelial cells are normally generated, but their postnatal development is arrested in the absence of ZBTB20, as manifested by an immature appearance of the organ of Corti, malformation of tectorial membrane (TM), a flattened spiral prominence (SP), and a lack of identifiable Boettcher cells. Furthermore, these defects are related with a failure in the terminal differentiation of the nonsensory epithelium covering the outer border Claudius cells, outer sulcus root cells, and SP epithelial cells. Transcriptome analysis shows that ZBTB20 regulates genes encoding for TM proteins in the greater epithelial ridge, and those preferentially expressed in root cells and SP epithelium. Our results point to ZBTB20 as an essential regulator for postnatal cochlear maturation and particularly for the terminal differentiation of cochlear lateral nonsensory domain.


Asunto(s)
Cóclea , Células Ciliadas Auditivas , Animales , Ratones , Cóclea/metabolismo , Células Ciliadas Auditivas/fisiología , Audición/fisiología , Mamíferos , Ganglio Espiral de la Cóclea , Factores de Transcripción/genética , Factores de Transcripción/metabolismo
15.
Vaccines (Basel) ; 11(5)2023 May 12.
Artículo en Inglés | MEDLINE | ID: mdl-37243080

RESUMEN

(1) Background: To explore the influencing factors of human papillomavirus (HPV) vaccination among mothers and daughters so as to provide evidence and strategies for improving the HPV vaccination rate of 9-18-years-old girls. (2) A questionnaire survey was conducted among the mothers of 9-18-year-old girls from June to August 2022. The participants were divided into the mother and daughter vaccinated group (M1D1), the mother-only vaccinated group (M1D0), and the unvaccinated group (M0D0). Univariate tests, the logistic regression model, and the Health Belief Model (HBM) were employed to explore the influencing factors. (3) Results: A total of 3004 valid questionnaires were collected. According to the regions, Totally 102, 204, and 408 mothers and daughters were selected from the M1D1, M1D0, and M0D0 groups, respectively. The mother having given her daughter sex education (OR = 3.64; 95%CI 1.70, 7.80), the mother's high perception of disease severity (OR = 1.79; 95%CI 1.02, 3.17), and the mother's high level of trust in formal information (OR = 2.18; 95%CI 1.26, 3.78) were all protective factors for both the mother and her daughter's vaccination. The mother's rural residence (OR = 0.51; 95%CI 0.28, 0.92) was a risk factor for vaccination of both mother and daughter. The mother's education of high school or above (OR = 2.12; 95%CI 1.06, 4.22), the mother's high level of HPV and HPV vaccine knowledge (OR = 1.72; 95%CI 1.14, 2.58), and the mother's high level of trust in formal information (OR = 1.72; 95%CI 1.15, 2.57) were protective factors of mother-only vaccination. The older the mother (OR = 0.95; 95%CI 0.91, 0.99) was classed as a risk factor for mother-only vaccination. "Waiting until the daughters are older to receive the 9-valent vaccine" is the main reason why the daughters of M1D0 and M0D0 are not vaccinated". (4) Chinese mothers had a high willingness to vaccinate their daughters with the HPV vaccine. The higher education level of the mother, giving sex education to the daughter, the older ages of mothers and daughters, the mother's high level of HPV and HPV vaccine knowledge, a high level of perception of the disease severity, and a high level of trust in formal information were promoting factors of HPV vaccination for mother and daughter, and rural residence was a risk factor to vaccination. To promote HPV vaccination in girls from 9-18 years old, communities could provide health education to rural mothers with low education levels; the government could advocate for HPV vaccination through issuing policy documents; and doctors and the CDC could popularize the optimal age for HPV vaccination to encourage mothers to vaccinate their daughters at the age of 9-14 years old.

16.
Zhen Ci Yan Jiu ; 48(4): 353-8, 2023 Apr 25.
Artículo en Chino | MEDLINE | ID: mdl-37186199

RESUMEN

OBJECTIVE: To observe the effects of electroacupuncture (EA) penetration needling on Toll-like receptors 4/myeloid differentiation factor 88/nuclear factor-kappa B (TLR4/MyD88/NF-κB) signaling pathway in rat synovium and the serum-related inflammatory factors, so as to explore the mechanism of EA penetration needling on synovial inflammation in rats with knee osteoarthritis (KOA). METHODS: SD male rats were randomly divided into sham-operation group, model group, EA+penetration needling group, and conventional EA group, with 16 rats in each group. The rats model was prepared by anterior cruciate ligment transection and these rats were forced to exercise for 8 weeks after operation. After successful modeling, in the EA+penetration needling group, the needles were inserted at "Dubi" (ST35) "Neixiyan" (EX-LE4), and at "Xuehai"(SP10) "Liangqiu"(ST34) on the right hind limb, towards each other, 5-8 mm in depth, respectively. In the conventional EA group, the needles were inserted at ST35 and EX-LE4 on the right hind limb, obliquely, at 30° angle to the skin, 3-5 mm in depth; and were inserted at SP10 and ST34 on the right hind limb perpendicularly, 3-5 mm in depth. In these two groups, electric stimulation was operated with dense-disperse wave, 2 Hz/10 Hz in frequency and 0.5-1.5 mA in intensity, retained for 20 min in each treatment. The treatment was given once daily, 10 days as 1 course of treatment, and 2 courses were required at the interval of 2 days. After the intervention, the knee joint effusion was observed by musculoskeletal ultrasound; the contents of IL-1ß, IL-6 and TNF-α in serum were determined by ELISA; the morphological changes in the synovium were observed after H.E. staining; the positive expression of NF-κB p65 in the synovial membrane was detected by immunohistochemical method; the expression levels of TLR4, MyD88, TRAF-6 and NF-κB p65 proteins in the synovial membrane were determined by Western blot. RESULTS: Compared with the sham-operation group, in the model group, the knee joint effusion was obviously increased, the synovial lining cells were distributed irregularly, the cells were disarranged, the pannus was formed largely, and a great number of the inflammatory cells were infiltrated; the contents of serum IL-1ß, IL-6 and TNF-α, the positive expression of NF-κB p65, the protein expression levels of TLR4, MyD88, TRAF-6 and NF-κB p65 in the synovial tissue were increased (P<0.05). Compared with the model group, the knee joint effusion was reduced, the synovial lining cells were proliferated, a small number of the inflammatory cells were infiltrated, and the pannus was formed lightly; the contents of serum IL-1ß, IL-6 and TNF-α, the positive expression of NF-κB p65, the protein expression levels of TLR4, MyD88, TRAF-6 and NF-κB p65 in the synovial tissue were lower (P<0.05) in the EA+penetration needling group and the conventional EA group. In the conventional EA group, the knee joint effusion was increased, the synovial lining cells were proliferated, the inflammatory cells were infiltrated largely, and the pannus was formed increasingly; the contents of serum IL-1ß, IL-6 and TNF-α, and the protein expression levels of TLR4, MyD88 and NF-κB p65 in the synovial tissue were increased when compared with the EA+penetration needling group (P<0.05). CONCLUSION: The EA+penetration needling can significantly relieve the synovial inflammatory reaction and the knee joint effusion in KOA rats. The mechanism is probably related to down-regulating the downstream inflammatory cascade through inhibiting the transduction of TLR4/MyD88/NF-κB signaling pathway.


Asunto(s)
Electroacupuntura , Osteoartritis de la Rodilla , Ratas , Masculino , Animales , FN-kappa B/genética , FN-kappa B/metabolismo , Factor 88 de Diferenciación Mieloide/genética , Factor 88 de Diferenciación Mieloide/metabolismo , Osteoartritis de la Rodilla/genética , Osteoartritis de la Rodilla/terapia , Receptor Toll-Like 4/genética , Receptor Toll-Like 4/metabolismo , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo , Interleucina-6/metabolismo , Transducción de Señal , Inflamación/genética , Inflamación/terapia
17.
J Chem Phys ; 158(17)2023 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-37125721

RESUMEN

A wide spectrum of state-of-the-art characterization techniques have been devised to monitor the electrode-electrolyte interface that dictates the performance of electrochemical devices. However, coupling multiple characterization techniques to realize in situ multidimensional analysis of electrochemical interfaces remains a challenge. Herein, we presented a hyphenated differential electrochemical mass spectrometry and attenuated total reflection surface enhanced infrared absorption spectroscopy analytical method via a specially designed electrochemical cell that enables a simultaneous detection of deposited and volatile interface species under electrochemical reaction conditions, especially suitable for non-aqueous, electrolyte-based energy devices. As a proof of concept, we demonstrated the capability of the homemade setup and obtained the valuable reaction mechanisms, by taking the tantalizing reactions in non-aqueous lithium-ion batteries (i.e., oxidation and reduction processes of carbonate-based electrolytes on Li1+xNi0.8Mn0.1Co0.1O2 and graphite surfaces) and lithium-oxygen batteries (i.e., reversibility of the oxygen reaction) as model reactions. Overall, we believe that the coupled and complementary techniques reported here will provide important insights into the interfacial electrochemistry of energy storage materials (i.e., in situ, multi-dimensional information in one single experiment) and generate much interest in the electrochemistry community and beyond.

18.
Eur J Med Chem ; 254: 115349, 2023 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-37060754

RESUMEN

A series of chromone-oxime derivatives containing piperazine sulfonamide moieties were designed, synthesized and evaluated for their inhibitory activities against IDO1. These compounds displayed moderate to good inhibitory activity against IDO1 with IC50 values in low micromolar range. Among them, compound 10m bound effectively to IDO1 with good inhibitory activities (hIDO1 IC50 = 0.64 µM, HeLa IDO1 IC50 = 1.04 µM) and were selected for further investigation. Surface plasmon resonance analysis confirmed the direct interaction between compound 10m and IDO1 protein. Molecular docking study of the most active compound 10m revealed key interactions between 10m and IDO1 in which the chromone-oxime moiety coordinated to the heme iron and formed several hydrogen bonds with the porphyrin ring of heme and ALA264, consistent with the observation by UV-visible spectra that 10m induced a Soret peak shift from 403 to 421 nm. Moreover, compound 10m exhibited no cytotoxicity at its effective concentration in MTT assay. Consistently, in vivo assays results demonstrated that 10m displayed potent antitumor activity with low toxicity in CT26 tumor-bearing Balb/c mice, in comparison with 1-methyl-l-tryptophan (1-MT) and 4-amino-N-(3-chloro-4-fluorophenyl)-N'-hydroxy-1,2,5-oxadiazole-3-carboximidamide (IDO5L). In brief, the results suggested that chromone-oxime derivatives containing sulfonamide moieties might serve as IDO1 inhibitors for the development of new antitumor agents.


Asunto(s)
Inhibidores Enzimáticos , Indolamina-Pirrol 2,3,-Dioxigenasa , Animales , Ratones , Relación Estructura-Actividad , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , Simulación del Acoplamiento Molecular , Oximas/farmacología , Hemo , Sulfonamidas/farmacología
19.
Front Behav Neurosci ; 17: 1107265, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36873772

RESUMEN

The incidence of major depressive disorder (MDD) is increasing all over the world. There is a great need for complementary or alternative therapies with high safety, few side effects, and precise efficacy to care for MDD. In China, acupuncture has significant laboratory data and clinical trials to demonstrate its antidepressant efficacy. However, there is no clear answer as to how it works. Exosomes are membranous vesicles that rely on cellular multivesicular bodies (MVBs) fused to the cell membrane for release into the extracellular matrix. Almost all cell types are capable of producing and releasing exosomes. As a result, exosomes contain complex RNAs and proteins from their relatives (Cells that secretes exosomes). They can cross biological barriers and participate in biological activities, such as cell migration, angiogenesis, and immune regulation. These properties have made them a popular research topic. Some experts have suggested that exosomes may serve as delivery vehicles for acupuncture to work. This presents both an opportunity and a new challenge for improving the protocols of acupuncture as a treatment for MDD. To better define the relationship between MDD, exosomes, and acupuncture, we reviewed the literature from the last few years. Inclusion criteria included randomized controlled trials and basic trials evaluating acupuncture in the treatment or prevention of MDD, the role of exosomes in the development and progression of MDD, and the role of exosomes in acupuncture. We believe that acupuncture may affect the distribution of exosomes in vivo, and exosomes may be a new carrier for acupuncture treatment of MDD in the future.

20.
Surg Endosc ; 37(6): 4737-4747, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36890418

RESUMEN

BACKGROUND: The natural course of gastric low-grade dysplasia (LGD) remains unclear, and there are inconsistent management recommendations among guidelines and consensus. OBJECTIVE: This study aimed to investigate the incidence of advanced neoplasia in patients with gastric LGD and identify the related risk factors. METHODS: Cases of biopsy demonstrated LGD (BD-LGD) at our center from 2010 to 2021 were reviewed retrospectively. Risk factors related to histological progression were identified, and outcomes of patients based on risk stratification were evaluated. RESULTS: Ninety-seven (23.0%) of 421 included BD-LGD lesions were diagnosed as advanced neoplasia. Among 409 superficial BD-LGD lesions, lesion in the upper third of the stomach, H. pylori infection, larger size, and narrow band imaging (NBI)-positive findings were independent risk factors of progression. NBI-positive lesions and NBI-negative lesions with or without other risk factors had 44.7%, 1.7%, and 0.0% risk of advanced neoplasia, respectively. Invisible lesions, visible lesions (VLs) without a clear margin, and VLs with a clear margin and size ≤ 10 mm, or > 10 mm had 4.8%, 7.9%, 16.7%, and 55.7% risk of advanced neoplasia, respectively. In addition, endoscopic resection decreased the risk of cancer (P < 0.001) and advanced neoplasia (P < 0.001) in patients with NBI-positive lesions, but not in NBI-negative patients. Similar results were found in patients with VLs with clear margin and size > 10 mm. Moreover, NBI-positive lesions had higher sensitivity and lower specificity for predicting advanced neoplasia than VLs with a clear margin and size > 10 mm determined by white-light endoscopy (97.6% vs. 62.7%, P < 0.001; and 63.0% vs. 85.6%, P < 0.001, respectively). CONCLUSION: Progression of superficial BD-LGD is associated with NBI-positive lesions, as well as with VLs with a clear margin (size > 10 mm) if NBI is unavailable, and selective resection of those lesions offers benefits for patients by decreasing the risk of advanced neoplasia.


Asunto(s)
Lesiones Precancerosas , Neoplasias Gástricas , Humanos , Estudios Retrospectivos , Endoscopía/métodos , Factores de Riesgo , Estómago/patología , Lesiones Precancerosas/diagnóstico por imagen , Lesiones Precancerosas/cirugía , Neoplasias Gástricas/etiología , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/patología , Imagen de Banda Estrecha
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