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1.
Int J Ophthalmol ; 17(8): 1396-1402, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39156779

RESUMEN

AIM: To investigate the therapeutic effects of hydrogel dressings on neurotrophic keratitis in rats. METHODS: Male Wistar rats, aged 42-56d, were randomly divided into control, experimental, and treatment groups, each consisting of five rats. The experimental and treatment groups underwent neurotrophic keratitis modeling in both eyes. After successful modeling, biomedical hydrogels formed with polyvinyl alcohol and polyvinyl pyrrolidone were used in treatment group for 7d. Ocular irritation response and keratitis index scores, Schirmer's test, tear film break-up time (BUT), sodium fluorescein staining, and hematoxylin and eosin (HE) staining were used to evaluate the effectiveness of the treatment. RESULTS: The neurotrophic keratitis model was successfully established in rats with severe ophthalmic nerve injury, characterized by keratitis, ocular irritation, reduced tear secretion measured by decreased BUT and Schirmer test values, corneal epithelial loss, and disorganized collagen fibers in the stromal layer. Following treatment with hydrogel dressings, significant improvements were observed in keratitis scores and ocular irritation symptoms in model eyes. Although the recovery of tear secretion, as measured by the Schirmer's test, did not show statistical differences, BUT was significantly prolonged. Fluorescein staining confirmed a reduction in the extent of corneal epithelial loss after treatment. HE staining revealed the restoration of the structural disorder in both the epithelial and stromal layers to a certain extent. CONCLUSION: Hydrogel dressing reduces ocular surface irritation, improves tear film stability, and promotes the repair and restoration of damaged epithelial cells by maintaining a moist and clean environment on the ocular surface in the rat model.

2.
Chem Sci ; 15(32): 13058-13067, 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39148788

RESUMEN

Organohalides are vital organic building blocks with applications spanning various fields. However, direct halogenation of certain neutral or unreactive substrates by using solely the regular halogenating reagents has proven challenging. Although various halogenation approaches via activating halogenating reagents or substrates have emerged, a catalytic system enabling broad substrate applicability and diverse halogenation types remains relatively underexplored. Inspired by the halogenation of arenes via thianthrenation of arenes, here we report that thianthrene, in combined use with trifluoromethanesulfonic acid (TfOH), could work as an effective catalytic system to activate regular halogenating reagents (NXS). This new protocol could accomplish multiple types of halogenation of organic compounds including aromatics, olefins, alkynes and ketones. The mechanism study indicated that a highly reactive electrophilic halogen thianthrenium species, formed in situ from the reaction of NXS with thianthrene in the presence of TfOH, was crucial for the efficient halogenation process.

3.
Int J Surg Case Rep ; 122: 110183, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39154566

RESUMEN

INTRODUCTION AND IMPORTANCE: Postoperative visual loss (POVL) is a relatively rare but devastating complication. We reported a case of POVL after spine surgery caused by ischemia of retina and optic nerve, and firstly introduced the possibility of cavernous sinus thrombosis in POVL development. CASE PRESENTATION: A 67-year-old woman diagnosed with "lumbar spinal stenosis" was admitted to undergo posterior lumbar spinal canal decompression surgery because of the persistent lumbago and numbness. The operation was performed in the prone position under general anesthesia uneventfully. On the second day, the visual acuity of her right eye suddenly decreased to no light perception. The ophthalmic examination indicated edematous eyelid, chemosis, ptosis, ophthalmoplegia, relative afferent pupillary defect and higher orbital pressure in her affected eye, and funduscopic examination revealed pale optic disc, diffuse retinal welling and attenuated arteries. Cerebral magnetic resonance angiography implied the stenosis of cavernous sinus segment of right internal carotid artery. Aseptic cavernous sinus thrombosis and the secondary combined occlusion of central retinal and optic nerve vessels were suspected. Therefore, anticoagulation, vasodilation, oxygen and anti-inflammation treatment were timely administrated. One month after the treatment, swelling eyelid and ocular motion had markedly improved. However, there was no remarkable improvement in the patient's visual acuity. CLINICAL DISCUSSION: Postoperative visual loss (POVL) after spine surgery is regarded as a serious complication with irreversible vision damage. It was alarming that cavernous sinus thrombosis might be a possible cause of POVL. High-volume fluid replacement, unstable hemodynamic parameters, prone position and prolonged surgical duration might bring about microvascular diseases and hypercoagulable state, contributing to the occurrence of POVL. CONCLUSION: Our study firstly implied the possibility of cavernous sinus thrombosis in the POVL development. Detailed assessment, fluids management, hemodynamic stabilizing and duration optimization were proposed for POVL prevention.

4.
Wei Sheng Yan Jiu ; 53(4): 540-546, 2024 Jul.
Artículo en Chino | MEDLINE | ID: mdl-39155220

RESUMEN

OBJECTIVE: To explore whether tea polyphenols(TP) improve sarcopenia in the aged type 2 diabetes(T2DM)model rats via mitochondrial quality control(MQC). METHODS: A total of 55 2-month-old male SD rats were randomly divided into the control group(n=10), the aged model group(aged, n=10) and the aging T2DM model group(n=35). The aging T2DM model group rats were fed with high-sugar and high-fat diet and intraperitoneally injected with 50 mg/kg D-galactose daily. After 4 weeks, the aging T2DM model group rats were given a single intraperitoneal injection of 30 mg/kg streptozotocin(STZ). After STZ injection for 2 weeks, fasting blood glucose(FBG) ≥ 16.7 mmol/L was defined as successful T2DM model. When the model was successfully induced, the 30 model rats were randomly divided into aged T2DM group(Mod), 300 mg/kg TP teatment group(TP) and 3 mg/kg rosiglitazone treatment group(RSG) according to FBG, with 10 rats in each group. Each group was treated with 50 mg/kg D-galactose to induce senescence and fed with high glucose and fat for 8 weeks. Western blot was used to detect the expression of P53 protein in gastnemius muscle tissue of the model group at the end of the experiment, which was higher than that of the control group, indicating that the aging T2DM model was successfully established. FBG was detected by the blood glucose meter, gastnemius muscle relative weights was calculated, the microstructure of mitochondria of gastnemius muscle was observed by transmission electron microscope(TEM), the expression of mitochondrial biosynthesis-related proteins PGC-1α, mitochondrial dynamics-related proteins(OPA1, DRP1) and mitochondrial autophagy-related proteins(P62, LC3) in gastnemius muscle were detected by western blot. RESULTS: Compared with the control group, the level of FBG and the expression of P53 in the Mod group were increased(P<0.01). The gastnemius muscle relative weights, the expression level of PGC-1α, OPA1 and the ratio of LC3II/LC3I were decreased(P<0.01). The expression level of P62 and DRP1 were significantly increased(P<0.01). The number of mitochondria decreased, the volume decreased and a large number of vacuolization, and there were no obvious autophagolysosomes and fission and fusion. After 8 weeks, compared with the Mod group, the number of mitochondria in the gastrocnemius of TP and RSG groups, vacuolization, fission and fusion were improved, and the autophagolysosomes was significantly increased. The expression levels of P53, DRP1 and P62, the level of FBG in the TP group were significantly decreased(P<0.01, P<0.05). The expression levels of OPA1 and PGC-1α, the ratios of LC3II/LC3I and gastnemius muscle relative weights were significantly increased(P<0.05, P<0.01). CONCLUSION: TP can improve the sarcopenia in the aged T2DM model rats, and its mechanism is related to the regulation of mitochondrial quality control.


Asunto(s)
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Polifenoles , Ratas Sprague-Dawley , Sarcopenia , , Animales , Masculino , Polifenoles/farmacología , Ratas , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Té/química , Sarcopenia/prevención & control , Sarcopenia/metabolismo , Sarcopenia/tratamiento farmacológico , Sarcopenia/etiología , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/tratamiento farmacológico , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Envejecimiento , Modelos Animales de Enfermedad , Músculo Esquelético/metabolismo , Músculo Esquelético/efectos de los fármacos
5.
Curr Neuropharmacol ; 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39150031

RESUMEN

BACKGROUND: Administration of olanzapine (OLA) is closely associated with obesity and glycolipid abnormalities in patients with schizophrenia (SCZ), although the exact molecular mecha- nisms remain elusive. OBJECTIVE: We conducted comprehensive animal and molecular experiments to elucidate the mecha- nisms underlying OLA-induced weight gain. METHODS: We investigated the mechanisms of OLA-induced adipogenesis and lipid storage by em- ploying a real-time ATP production rate assay, glucose uptake test, and reactive oxygen species (ROS) detection in 3T3-L1 cells and AMSCs. Rodent models were treated with OLA using various interven- tion durations, dietary patterns (normal diets/western diets), and drug doses. We assessed body weight, epididymal and liver fat levels, and metabolic markers in both male and female mice. RESULTS: OLA accelerates adipogenesis by directly activating glycolysis and its downstream PI3K sig- naling pathway in differentiated adipocytes. OLA promotes glucose uptake in differentiated 3T3-L1 preadipocytes. In mouse models with normal glycolipid metabolism, OLA administration failed to in- crease food intake and weight gain despite elevated GAPDH expression, a marker related to glycolysis and PI3K-AKT. This supports the notion that glycolysis plays a significant role in OLA-induced met- abolic dysfunction. CONCLUSION: OLA induces glycolysis and activates the downstream PI3K-AKT signaling pathway, thereby promoting adipogenesis.

6.
7.
8.
Commun Chem ; 7(1): 155, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38982259

RESUMEN

The existing hypervalent I(III) reagents bearing ONO2 group are limited in types and their applications primarily focused on the nitrooxylation reactions featuring a fully-exo fashion. Herein, a benziodazole-type O2NO-I(III) compound was prepared and its reaction with ß-monosubstituted enamines in the presence of CuI could trigger a radical nitration/cyclization/dehydration cascade to provide a series of less explored but biologically interesting furazan heterocycles. Mechanistically, the benziodazole-type O2NO-I(III) compound acts as a nitrating reagent and incorporates its NO moiety into the final furazan product in a fully-endo model, a process of which was proposed to involve nitration, cyclization and dehydration.

9.
Int J Biol Macromol ; 276(Pt 1): 133840, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39004250

RESUMEN

We previously found that modified citrus pectin (MCP), an inhibitor of pro-inflammatory factor Galectin-3 (Gal-3), has significant anti-inflammatory and chondroprotective effects. In this study, a hyaluronate (HA) gel-based sustained release system of MCP (MCP-HA) was developed as an anti-inflammatory agent for chronic inflammation for osteoarthritis (OA) treatment. The MCP-HA gel was injected into the knee joint cavities of OA rabbit models induced by anterior cruciate ligament transection (ACLT) or modified Hulth method once a week for five weeks. We found that MCP-HA could improve the symptoms and signs of OA, protect articular cartilage from degeneration, suppress synovial inflammation, and therefore alleviate OA progression. Proteomic analysis of the synovial fluid obtained from the knee joints of OA rabbits revealed that MCP-HA synergistically regulated the levels of multiple inflammatory mediators and proteins involved in metabolic pathways. Taken together, our results demonstrate that the MCP-HA shows a synergistic effect of HA and MCP by modulating both inflammation and metabolic processes, thereby alleviating OA progression. The MCP-HA sustained release system has promising potential for long-term use in OA treatment.


Asunto(s)
Ácido Hialurónico , Osteoartritis , Pectinas , Pectinas/farmacología , Pectinas/química , Pectinas/administración & dosificación , Animales , Ácido Hialurónico/farmacología , Ácido Hialurónico/química , Conejos , Inyecciones Intraarticulares , Osteoartritis/tratamiento farmacológico , Osteoartritis/patología , Geles , Modelos Animales de Enfermedad , Sinergismo Farmacológico , Masculino , Cartílago Articular/efectos de los fármacos , Cartílago Articular/patología , Cartílago Articular/metabolismo , Líquido Sinovial/metabolismo , Líquido Sinovial/efectos de los fármacos , Antiinflamatorios/farmacología , Antiinflamatorios/administración & dosificación
10.
Medicine (Baltimore) ; 103(29): e38965, 2024 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-39029008

RESUMEN

RATIONALE: Salivary duct carcinoma (SDC) is an aggressive form of cancer, with cutaneous metastasis being a rare occurrence. Furthermore, cutaneous metastasis of SDC secondary to a scald is even rarer, and to the best of our knowledge, our case represents the first such instance. Considering the involvement of the fingers in the metastatic site, which may affect limb function and quality of life, we present this case to explore the reason why scald could lead to distant recurrence and better treatment options. PATIENT CONCERNS: An 85-year-old man diagnosed with SDC in the parotid gland found enlarged masses at the fingertips as a consequence of a burn, 6 years after his initial treatment. DIAGNOSES: Cutaneous metastasis of SDC in the parotid gland and left thumb loss due to surgery. INTERVENTIONS: Radiotherapy was offered, targeting at the masses on the fingers, with dose at 15 Gy in 3 fractions, 12 Gy in 3 fractions, 15 Gy in 3 fractions for both hands and additional 21 Gy in 7 fractions only for left hand. OUTCOMES: The tumors shrank after 2 months of radiotherapy and the patient recovered well. Side effects included nail hyperplasia and paronychia. LESSONS: Connections between scald and distant metastasis of malignant tumors in this case needed further investigation. Considering reserving function of the fingers while dealing with metastasis, radiotherapy is recommended rather than surgery.


Asunto(s)
Dedos , Neoplasias Cutáneas , Anciano de 80 o más Años , Humanos , Masculino , Carcinoma Ductal/secundario , Carcinoma Ductal/patología , Carcinoma Ductal/terapia , Dedos/patología , Neoplasias de la Parótida/patología , Conductos Salivales/patología , Neoplasias de las Glándulas Salivales/patología , Neoplasias Cutáneas/secundario , Neoplasias Cutáneas/patología
11.
Beilstein J Org Chem ; 20: 1453-1461, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38952956

RESUMEN

A series of 4-thio/seleno-cyanated pyrazoles was conveniently synthesized from 4-unsubstituted pyrazoles using NH4SCN/KSeCN as thio/selenocyanogen sources and PhICl2 as the hypervalent iodine oxidant. This metal-free approach was postulated to involve the in situ generation of reactive thio/selenocyanogen chloride (Cl-SCN/SeCN) from the reaction of PhICl2 and NH4SCN/KSeCN, followed by an electrophilic thio/selenocyanation of the pyrazole skeleton.

12.
Front Neurosci ; 18: 1428987, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39050671

RESUMEN

Background: To quantify the changes in dynamic visual acuity (DVA) and explain the hidden reasons after acute exposure to hypobaric hypoxia status. Methods: The study group comprised 18 healthy male and 15 healthy female participants aged 20-24 years old. DVA was measured with the self-developed software of Meidixin (Tianjin) Co., Ltd. Measurements were taken at eight altitudes. Data analysis was performed using the Kolmogorov-Smirnov test, paired sample T-test, and two-way repeated measures analysis of variance (ANOVA) for repeated measurements. Results: At constant altitude, DVA showed an overall decreasing trend with increasing angular velocity and a fluctuating decrease at the vast majority of altitudes. At constant angular velocities, DVA gradually increased with altitude, with the most pronounced increase in DVA at altitude 5, and thereafter a gradual decrease in DVA as altitude increased. Finally, as altitude decreased, DVA increased again and reached a higher level at the end of the experiment, which was superior to the DVA in the initial state. Conclusion: Under a hypobaric hypoxic environment at high altitude, DVA was affected by the angular velocity and the degree of hypoxia, manifesting as an increase or decrease in DVA, which affects the pilot's observation of the display and control interfaces during the driving process, acquisition of information, and decision-making ability, which in turn may potentially jeopardize the safety of the flight.

13.
Front Public Health ; 12: 1344188, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38932774

RESUMEN

Objective: To evaluate parental knowledge of myopia control, investigate its association with children's practice and refractive status, and explore their change under the outbreak of COVID-19 pandemic. Methods: In this web-based survey, a self-administered questionnaire was made online available during the COVID-19 outbreak between February 1th, 2022 and August 31th, 2022 in China. Participants were recruited via social media by convenience and snowball sampling. Parents of both sexes whose children aged between 3 and 18 were eligible. The overall questionnaire was composed of four categories: demographic information, parental knowledge of myopia, children's myopia-related behaviors and their change after the COVID-19 pandemic, and children's refractive status. SPSS version 18.0 was applied to perform the statistics analysis and p < 0.05 was considered to be statistically significant. Results: A total of 423 eligible families were included in our online survey. The average age of children was 11.37 ± 2.83y (male 46.1%; female 53.9%), with a myopia incidence of 83.9% (355/423). Both children's age (OR = -0.6; 95%CI = -1.12 to -0.07; p = 0.026) and family income (OR = 2.60; 95%CI = 1.13 to 4.07; p = 0.001) had independently significant impacts on parental knowledge. Unexpectedly, parental knowledge was negatively correlated with children's onset age of myopia (p = 0.002, r = -0.165) and positively correlated with spectacles wearing (p = 0.014, r = 0.131), and no correlation was found between parental knowledge and the occurrence of children myopia, current diopter, annual myopia progression and the diopter of the first glasses (all p > 0.05). We found discordance phenomenon between parents' knowledge and children's behaviors, with parental knowledge being irrelevant to children's sleeping time (p = 0.159, r = 0.069), the frequency of lying reading (p = 0.462, r = -0.036) and keeping nutrition diet (p = 0.142, r = 0.072), and positively correlated with daily homework time (p = 0.012, r = 0.123). After the outbreak of COVID-19, 77.8% (329/423) of parents admitted that their children's daily routine had been changed, with children spending more time on sleeping (p < 0.001) and electronic products (p < 0.001), and taking less time to do outdoor activities (p < 0.001). Conclusion: The ideal interaction mode that establishing positive impact between parental knowledge and children practice has not been reached in China, which might be the result of insufficient parents' cognition and discordance phenomenon between parental knowledge and children's behaviors. The pandemic of COVID-19 has obviously changed children's daily routine. More efforts should be made to narrow the gap between knowledge and behaviors of myopia control, and stay alert to the potential increased risk of myopia during COVID-19.


Asunto(s)
COVID-19 , Conocimientos, Actitudes y Práctica en Salud , Miopía , Padres , Humanos , COVID-19/epidemiología , COVID-19/prevención & control , Miopía/epidemiología , Masculino , China/epidemiología , Femenino , Niño , Padres/psicología , Encuestas y Cuestionarios , Adolescente , Preescolar , Internet , Adulto , SARS-CoV-2
14.
Adipocyte ; 13(1): 2365211, 2024 12.
Artículo en Inglés | MEDLINE | ID: mdl-38858810

RESUMEN

microRNAs (miRNAs), a subclass of noncoding short RNAs, direct cells fate decisions that are important for cell proliferation and cell lineage decisions. Adipogenic differentiation contributes greatly to the development of white adipose tissue, involving of highly organized regulation by miRNAs. In the present study, we screened and identified 78 differently expressed miRNAs of porcine BMSCs during adipogenic differentiation. Of which, the role of miR-29c in regulating the proliferation and adipogenic differentiation was proved and detailed. Specifically, over-expression miR-29c inhibits the proliferation and adipogenic differentiation of BMSCs, which were reversed upon miR-29c inhibitor. Interference of IGF1 inhibits the proliferation and adipogenic differentiation of BMSCs. Mechanistically, miR-29c regulates the proliferation and adipogenic differentiation of BMSCs by targeting IGF1 and further regulating the MAPK pathway and the PI3K-AKT-mTOR pathway, respectively. In conclusion, we highlight the important role of miR-29c in regulating proliferation and adipogenic differentiation of BMSCs.


Asunto(s)
Adipogénesis , Diferenciación Celular , Proliferación Celular , Células Madre Mesenquimatosas , MicroARNs , Animales , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/citología , MicroARNs/genética , MicroARNs/metabolismo , Porcinos , Adipogénesis/genética , Células Cultivadas , Transducción de Señal , Adipocitos/citología , Adipocitos/metabolismo , Células de la Médula Ósea/citología , Células de la Médula Ósea/metabolismo
15.
Front Neurosci ; 18: 1321423, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38803687

RESUMEN

Purpose: To explore the influence of corneal higher-order aberrations (HOAs) on dynamic visual acuity (DVA) post cataract surgery. Methods: A total of 27 patients with 45 eyes following cataract surgery were included in this study. The postoperative monocular object-moving DVA at the velocity of 20, 40, and 80 degrees per second (dps) were examined at 1 month. The total corneal HOAs were measured with Scheimpflug-based corneal topography. The correlation between postoperative DVA and HOAs was analyzed. Results: Significant difference was shown among DVA at different velocities (P < 0.001). The 20 dps DVA was significantly better than 40 (P < 0.001) and 80 (P < 0.001) dps DVA. No significant difference was observed between 40 and 80 dps DVA (P = 0.420). The vertical coma and the root mean square (RMS) of coma (RMScoma) were statistically correlated with 80 dps DVA (P < 0.05). The vertical trefoil, RMStrefoil and total RMSHOA were statistically correlated with 40 and 80 dps DVA (P < 0.05). The spherical aberration was not significantly associated with postoperative DVA (P > 0.05 for all velocites). The multivariate linear regression model revealed that age was a significant influential factor for 20 dps DVA (P = 0.002), and RMStrefoil (4 mm) and age were significantly associated with 40 and 80 dps DVA (P ≤ 0.01). Conclusion: The research demonstrated that larger corneal HOAs, especially coma and trefoil aberrations were significantly associated with worse high-speed DVA, but not spherical aberration post cataract surgery.

16.
Oncol Lett ; 27(5): 215, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38572062

RESUMEN

[This retracts the article DOI: 10.3892/ol.2019.10331.].

17.
Nutr Neurosci ; : 1-17, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38622917

RESUMEN

OBJECTIVES: The study aimed to explore whether TP could improve memory in the aged type 2 diabetic rat model by regulating microbiota-immune-synaptic plasticity axis. METHODS: The experiment was divided into two parts. Firstly, to investigate the effects of TP on the physiopathology of the aged T2DM model rats, rats were randomly divided into the Normal control group, the aged group, the Aged T2DM model group, the TP 75, 150, 300 mg/kg groups, the 150 mg/kg Piracetam group and the 3 mg/kg Rosiglitazone group. Then, to further verify whether TP improved memory in aged T2DM rat model by regulating intestinal flora, the fecal microbiota transplantation (FMT) from the rats in the 300 mg/kg TP group into the rats in the aged T2DM model group was carried out. Effects on gut microbiota, colonic integrity (epithelial tight junction proteins), and endotoxemia (serum LPS) were examined, along with synaptic structure, synaptic plasticity-related structural proteins and inflammation signaling of the hippocampus in our study. RESULTS: Our results demonstrated that TP alleviated memory impairments in the aged T2DM rat model. The specific outcomes were as follows: TP 300 mg/kg corrected the gut dysbacteriosis, alleviated intestinal permeability reduction and peripheral/central inflammation, inhibited the TLR4/NF-κB signaling pathway. Meanwhile, TP improved the synaptic plasticity in the hippocampus of the aged T2DM model rats, whose expressions of SYN, PSD 95, NMDAR1 and GluR1 in hippocampus were significantly up-regulated. Surprisingly, rats of the FMT group displayed the same changes. DISCUSSION: TP improves the memory in aged T2DM rat model. The mechanism may be related to the alteration of gut flora, which can inhibit hippocampal TLR4/NF-κB signaling to attenuate neuroinflammation, then improve synaptic plasticity. The study proposes that TP interventions aimed at manipulating the gut microbiota may hold great potential as an effective approach for preventing and treating this disease.

18.
Org Biomol Chem ; 22(19): 3882-3886, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38656307

RESUMEN

The combining use of BnSCF2D, mCPBA and Tf2O serves as an efficient multi-component reagents system (MCRS) for the synthesis of deuteriodifluoromethylthiolated isocoumarins-1-imines/isocoumarins via intramolecular cyclization/deuteriodifluoromethylthiolation of 2-alkynylbenzamides/2-alkynylbenzoates. The approach features the generation of the crucial reactive electrophilic sulfonium salt through a sequence process involving the oxidation of BnSCF2D by mCPBA followed by Tf2O promoted activation.

19.
Toxicon ; 243: 107709, 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38615996

RESUMEN

Deoxynivalenol is a widespread feed contaminant that leads to vomit, which results in serious symptom such as increased intestinal permeability and even intestinal mucosal necrosis. Recent studies have reported the role of quercetin in alleviating deoxynivalenol-induced intestinal injury; however, the mechanisms and targets remain unclear. Thus, we aimed to identify the mechanisms of action by using a combination of network pharmacology and molecular docking. We identified 151 quercetin targets, 235 deoxynivalenol targets and 47 porcine intestinal injury targets by searching compound database and PubMed database, among which there were two common targets. The PPI network showed that the key proteins involved are NQO1 and PPAR-γ. The PPI network showed that the key proteins involved were NQO1 and PPARG. GO analysis found that genes were enriched primarily in response to oxidative stress. The PPI network showed that the key proteins involved are NQO1 and PPAR-γ. The genes are enriched primarily in response to oxidative stress. KEGG analysis showed enrichment of the HIF, reactive oxygen species and other signaling pathways. The molecular docking results indicated key binding activity between NQO1-quercetin and PPAR-γ-quercetin. By using network pharmacology, we have revealed the potential molecular mechanisms by which quercetin alleviates deoxynivalenol-induced porcine intestinal injury, which lays the foundation for the development of drugs to treat deoxynivalenol-induced intestinal injury in pigs.


Asunto(s)
Simulación del Acoplamiento Molecular , Farmacología en Red , PPAR gamma , Quercetina , Tricotecenos , Quercetina/farmacología , Animales , Tricotecenos/toxicidad , Porcinos , PPAR gamma/metabolismo , Estrés Oxidativo/efectos de los fármacos , Intestinos/efectos de los fármacos , NAD(P)H Deshidrogenasa (Quinona)/metabolismo , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo
20.
Wei Sheng Yan Jiu ; 53(1): 71-87, 2024 Jan.
Artículo en Chino | MEDLINE | ID: mdl-38443175

RESUMEN

OBJECTIVE: To investigate the effect of tea polyphenols(TP) on improving depression-like behavior in aged type 2 diabetes(T2DM) model rats. METHODS: A total of 40 8-week-old SD male rats were randomly divided into the control group(n=10) and the modeling group(n=30) according to the body weight. The rats in the modeling group were fed with high-glucose and high-fat diet and treated with 50 mg/kg D-galactose by intraperitoneal injection daily until the end of the experiment, while the rats in the control group were fed with the standard diet and treated with an equal volume of saline by intraperitoneal injection. After 4 weeks, the rats in the modeling group were injected with 25 mg/kg STZ, meanwhile the rats in the control group were injected with an equal volume of citric acid buffer. The level of fasting blood glucose(FBG) was measured on the 14~(th) day. When FBG≥16.7 mmol/L, the rats were identified as successful model of the T2DM rats. Then, the model rats were randomly divided into the model group, 150, 300 mg/kg TP groups(n=10, respectively), and the rats were given intragastric intervention for 8 weeks. The levels of the FBG were detected, and the depression-like behavior of rats was assessed by the open field test(OFT) and forced swimming test(FST). The density of microglia in hippocampus CA1 region was assessed by immunofluorescence staining, and protein expressions of P53, Iba1, iNOS, Arg-1 and BDNF were determined by western blot. RESULTS: Compared with the control group, the levels of FBG in the rats of the model group were obviously increased(P<0.01). In the OFT, the frequencies of rearing and grooming in the rats of model group markedly was decreased, while in the FST, the immobility time extensively was increased(P<0.01). The density of microglia in hippocampus CA1 region was increased(P<0.01). The expressions of P53, Iba1 and iNOS were increased, and the expressions of Arg-1 and BDNF were decreased(P<0.01). Additionally, compared with the model group, in the OFT, the frequencies of rearing and grooming were increased in the rats in 150 and 300 mg/kg TP group(P<0.01). The density of microglia in hippocampus CA1 region was decreased(P<0.01). The expressions of P53, Iba1 and iNOS were down-regulated, and the expression of BDNF was up-regulated(P<0.01). Additionally, compared with the model group, the levels of FBG was decreased in the rats in the 300 mg/kg TP group(P<0.01). The immobility time was decreased in the FST(P<0.01). The expression of Arg-1 was down-regulated(P<0.01). CONCLUSION: TP can improve depression-like behavior in aged T2DM model rats, and its mechanism may be related to regulate microglia M1/M2 polarization and up-regulate expression of BDNF in hippocampus.


Asunto(s)
Factor Neurotrófico Derivado del Encéfalo , Diabetes Mellitus Tipo 2 , Masculino , Animales , Ratas , Depresión/tratamiento farmacológico , Microglía , Proteína p53 Supresora de Tumor , Polifenoles/farmacología , Polifenoles/uso terapéutico ,
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