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1.
BMC Geriatr ; 24(1): 413, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38730354

ABSTRACT

BACKGROUND: There is growing evidence linking the age-adjusted Charlson comorbidity index (aCCI), an assessment tool for multimorbidity, to fragility fracture and fracture-related postoperative complications. However, the role of multimorbidity in osteoporosis has not yet been thoroughly evaluated. We aimed to investigate the association between aCCI and the risk of osteoporosis in older adults at moderate to high risk of falling. METHODS: A total of 947 men were included from January 2015 to August 2022 in a hospital in Beijing, China. The aCCI was calculated by counting age and each comorbidity according to their weighted scores, and the participants were stratified into two groups by aCCI: low (aCCI < 5), and high (aCCI ≥5). The Kaplan Meier method was used to assess the cumulative incidence of osteoporosis by different levels of aCCI. The Cox proportional hazards regression model was used to estimate the association of aCCI with the risk of osteoporosis. Receiver operating characteristic (ROC) curve was adapted to assess the performance for aCCI in osteoporosis screening. RESULTS: At baseline, the mean age of all patients was 75.7 years, the mean BMI was 24.8 kg/m2, and 531 (56.1%) patients had high aCCI while 416 (43.9%) were having low aCCI. During a median follow-up of 6.6 years, 296 participants developed osteoporosis. Kaplan-Meier survival curves showed that participants with high aCCI had significantly higher cumulative incidence of osteoporosis compared with those had low aCCI (log-rank test: P < 0.001). When aCCI was examined as a continuous variable, the multivariable-adjusted model showed that the osteoporosis risk increased by 12.1% (HR = 1.121, 95% CI 1.041-1.206, P = 0.002) as aCCI increased by one unit. When aCCI was changed to a categorical variable, the multivariable-adjusted hazard ratios associated with different levels of aCCI [low (reference group) and high] were 1.00 and 1.557 (95% CI 1.223-1.983) for osteoporosis (P <  0.001), respectively. The aCCI (cutoff ≥5) revealed an area under ROC curve (AUC) of 0.566 (95%CI 0.527-0.605, P = 0.001) in identifying osteoporosis in older fall-prone men, with sensitivity of 64.9% and specificity of 47.9%. CONCLUSIONS: The current study indicated an association of higher aCCI with an increased risk of osteoporosis among older fall-prone men, supporting the possibility of aCCI as a marker of long-term skeletal-related adverse clinical outcomes.


Subject(s)
Accidental Falls , Osteoporosis , Humans , Male , Aged , Osteoporosis/epidemiology , Osteoporosis/diagnosis , Retrospective Studies , Aged, 80 and over , Incidence , Risk Assessment/methods , Risk Factors , Comorbidity , China/epidemiology , Age Factors
2.
J Integr Med ; 22(3): 279-285, 2024 May.
Article in English | MEDLINE | ID: mdl-38688809

ABSTRACT

BACKGROUND: Yiqi Peiyuan (YQPY) prescription, a composite prescription of traditional Chinese medicine, has been used to prevent or delay the continued deterioration of renal function after acute kidney injury (AKI) in some institutions and has shown considerable efficacy. OBJECTIVE: This is the first randomized controlled trial to assess efficacy and safety of YQPY for improving short-term prognosis in adult patients with AKI. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: This is a prospective, double-blind, multicenter, randomized, and placebo-controlled clinical trial. A total of 144 enrolled participants were randomly allocated to two groups according to a randomization schedule. Participants, caregivers and investigators assessing the outcomes were blinded to group assignment. Patients in the YQPY group received 36 g YQPY granules twice a day for 28 days. Patients in the placebo group received a placebo in the same dose as the YQPY granules. MAIN OUTCOME MEASURES: The primary outcome was the change in the estimated glomerular filtration rate (eGFR) between baseline and after 4 and 24 weeks of treatment. The secondary outcomes were the change of serum creatinine (Scr) level between baseline and after treatment, and the incidence of endpoint events, defined as eGFR increasing by more than 25% above baseline, eGFR >75 mL/min per 1.73 m2 or the composite endpoint, which was defined as the sum of patients meeting either of the above criteria. RESULTS: Data from a total of 114 patients (59 in the YQPY group and 55 in the control group) were analyzed. The mean changes in eGFR and Scr in weeks 4 and 24 had no difference between the two groups. In further subgroup analysis (22 in the YQPY group and 31 in the control group), the mean change in eGFR after treatment for 4 weeks was 27.39 mL/min per 1.73 m2 in the YQPY group and 5.78 mL/min per 1.73 m2 in the placebo group, and the mean difference between groups was 21.61 mL/min per 1.73 m2 (P < 0.001). Thirteen (59.1%) patients in the YQPY group and 5 (16.1%) in the placebo group reached the composite endpoints (P = 0.002). During the intervention, 2 and 4 severe adverse events were reported in the YQPY and placebo groups, respectively. CONCLUSION: The YQPY granules can effectively improve the renal function of patients 4 weeks after the onset of AKI, indicating that it has good efficacy for improving short-term renal outcomes in patients with AKI. The YQPY granules may be a promising therapy for adults with AKI. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100051723. Please cite this article as: Wu JJ, Zhang TY, Qi YH, Zhu MY, Fang Y, Qi CJ, Cao LO, Lu JF, Lu BH, Tang LM, Shen JX, Mou S. Efficacy and safety of Yiqi Peiyuan granules for improving the short-term prognosis of patients with acute kidney injury: a multicenter, double-blind, placebo-controlled, randomized trial. J Integr Med. 2024; 22(3): 279-285.


Subject(s)
Acute Kidney Injury , Drugs, Chinese Herbal , Glomerular Filtration Rate , Humans , Male , Acute Kidney Injury/drug therapy , Female , Double-Blind Method , Drugs, Chinese Herbal/therapeutic use , Drugs, Chinese Herbal/adverse effects , Drugs, Chinese Herbal/administration & dosage , Middle Aged , Glomerular Filtration Rate/drug effects , Aged , Prognosis , Prospective Studies , Treatment Outcome , Adult , Creatinine/blood
3.
Medicina (Kaunas) ; 60(3)2024 Mar 18.
Article in English | MEDLINE | ID: mdl-38541224

ABSTRACT

Background and Objectives: This study examined the influence of stationary bikes and elliptical machines on knee movement and joint load during exercise. Materials and Methods: Twelve healthy male participants engaged in pedaling exercises on stationary bikes and elliptical machines at speeds of 50 and 70 revolutions per minute (rpm). Knee movement and joint load were assessed using a motion analysis system. Results: The results indicated that elliptical machines induced higher knee joint torque compared to stationary bikes. Notably, peak torque occurred at different joint angles, with stationary bikes reaching an earlier peak at 70°-110° and elliptical machines showing a later peak at 135°-180°. Increased pedaling speed correlated with higher peak knee joint torque on both machines. With the elliptical machine, a higher pedaling frequency correlated with increased peak forces on the knee and ankle joints, as well as vertically. Interestingly, both types of equipment were associated with enhanced peak knee joint torques during high-speed pedaling. Conversely, constant pedaling on elliptical machines limited the ankle angle and could induce inward rotation. Conclusions: This study focused on knee joint torque variations during pedaling on indoor stationary bicycles and elliptical machines. Elliptical machines showed higher peak values of forces and torque, particularly during the propulsive and recovery phases, indicating potential challenges to the knee joint. Notably, peak pedal angles occurred earlier on indoor stationary bicycles, emphasizing the impact of equipment choice on joint kinetics.


Subject(s)
Bicycling , Knee Joint , Humans , Male , Biomechanical Phenomena , Knee , Lower Extremity
4.
Am J Hypertens ; 2024 Mar 09.
Article in English | MEDLINE | ID: mdl-38459938

ABSTRACT

The effectiveness of Renal Denervation (RDN) in reducing blood pressure and systemic sympathetic activity in hypertensive patients has been established. However, the underlying central mechanism remains unknown. This study aimed to investigate the role of RDN in regulating cardiovascular function via the central Renin-Angiotensin System (RAS) pathway. Ten-week-old Spontaneously Hypertensive Rats (SHR) were subjected to Selective Afferent Renal Denervation (ADN) using capsaicin solution. We hypothesized that ADN would effectively reduce blood pressure and rebalance the RAS component of PVN in SHR. The experimental results show that ADN group exhibited significantly lower blood pressure, reduced systemic sympathetic activity, decreased chronic neuronal activation marker C-FOS expression in the paraventricular nucleus of hypothalamus (PVN), and improved arterial baroreflex function, compared with the Sham group. Furthermore, ACE and AT1 protein expression was reduced while ACE2 and MAS protein expression was increased in the PVN of SHR after ADN. These findings suggest that RDN may exert these beneficial effects through modulating the central RAS pathway.

5.
Transl Psychiatry ; 14(1): 21, 2024 Jan 10.
Article in English | MEDLINE | ID: mdl-38199983

ABSTRACT

High suicide risk represents a serious problem in patients with major depressive disorder (MDD), yet treatment options that could safely and rapidly ameliorate suicidal ideation remain elusive. Here, we tested the feasibility and preliminary efficacy of the Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT) in reducing suicidal ideation in patients with MDD. Thirty-two MDD patients with moderate to severe suicidal ideation participated in the current study. Suicidal ideation and depression symptoms were assessed before and after 5 days of open-label SAINT. The neural pathways supporting rapid-acting antidepressant and suicide prevention effects were identified with dynamic causal modelling based on resting-state functional magnetic resonance imaging. We found that 5 days of SAINT effectively alleviated suicidal ideation in patients with MDD with a high response rate of 65.63%. Moreover, the response rates achieved 78.13% and 90.63% with 2 weeks and 4 weeks after SAINT, respectively. In addition, we found that the suicide prevention effects of SAINT were associated with the effective connectivity involving the insula and hippocampus, while the antidepressant effects were related to connections of the subgenual anterior cingulate cortex (sgACC). These results show that SAINT is a rapid-acting and effective way to reduce suicidal ideation. Our findings further suggest that distinct neural mechanisms may contribute to the rapid-acting effects on the relief of suicidal ideation and depression, respectively.


Subject(s)
Depressive Disorder, Major , Humans , Depressive Disorder, Major/diagnostic imaging , Depressive Disorder, Major/therapy , Suicidal Ideation , Hippocampus , Magnetic Resonance Imaging , Antidepressive Agents/therapeutic use
7.
Chinese Pharmacological Bulletin ; (12): 125-132, 2024.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1013614

ABSTRACT

Aim To prepare tripterygium glycoside nanoparticles and probe into their therapeutic effect on collagen-induced arthritis ( CIA) rats. Methods Tripterygium glycosides polyglycoside nanoparticles were prepared by thin film dispersion method and their quality was assessed. The CIA model was established and drug intervention performed. The body weight, toe swelling degree and arthritis index were measured. The pathological changes of the organs, knee and ankle synovium were observed. The serum levels of kidney function and inflammatory cytokine expression were detected in rats. Results The prepared tripterygium wil-fordii polyglycoside nanoparticles were round particles with uniform distribution and stable properties under electron microscope. Compared with the model group, the swelling of the left and right toes of medication group significantly decreased (P < 0. 01), and the ar-thritis index markedly decreased ( P < 0. 01). Among them, the efficacy of the TG-NPs group was better than that of the TG group. Compared with the normal group, the indexes of heart, spleen, kidney and testis all significantly decreased (P <0. 05, P<0.01). TG-NPs group had a significantly reduced pathological ankle-joint injury in knee cartilage and increased apoptotic synovial cells. Compared with the model group, the serum levels of ALT and BUN and CRE in TG-NPs group were significantly lower (P < 0. 05 ), and IL-1β, TNF-α and IL-6 levels decreased significantly (P <0. 05). Conclusions TG-NPs have good therapeutic effect on CIA through induction of synovial cell apoptosis and decrease of the expression of inflammatory cytokines. By intravenous injection of blood circula-tion, slow and controlled release of drugs can be achieved, the first pass effect caused by oral drug can be avoided, the viscera toxicity can be reduced, which provides an experimental basis for the development of new nanoagents for the treatment of rheumatoid arthritis.

8.
Chinese Journal of School Health ; (12): 326-329, 2024.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1013492

ABSTRACT

Objective@#The study aims to investigate the impact of moderate intensity gymnastics on the development of executive function in children aged 5-6, thereby providing a theoretical foundation for exercise interventions targeting executive function.@*Methods@#A total of 63 preschool children, randomly seleted from 3 senior classes in a private kindergarten in Shangqiu, were randomly allocated to the intervention group ( n =31) and control group ( n =32). Children in the intervention group participated in 60 minute gymnastics at a moderate intensity, three times per week, for a total duration of 12 weeks. Concurrently, myzone technology was utilized to monitor exercise intensity throughout the entire intervention period. Children in the control group maintained their regular activities. Inhibitory control (Flanker task), working memory (Empty house task), and cognitive flexibility (Dots task) were assessed before and after the experiment.@*Results@#There was no statistically significant difference in the performance of inhibitory control, working memory, and cognitive flexibility tasks between the two groups of children before intervention ( P >0.05) .The results of covariance analysis revealed significant differences in reaction time [(782.88±24.29,805.13±23.74;719.90±119.99, 833.55± 177.87;1 042.39±72.75,1 091.29±49.42) ms] and accuracy[(73.86±7.26)%,(67.02±8.22)%;(86.36±7.63)%,( 80.50± 9.39 )%;(76.45±9.48)%,(69.59±7.66)%] across inhibitory control, working memory, and cognitive flexibility between the intervention group and the control group ( F =6.84, 4.50,4.87, 6.11, 3.74 , 5.06 , P <0.05). The intervention effect exhibited modest effects( d =0.17-0.74).@*Conclusions@#Moderate intensity gymnastics can make modest or moderate effect on improving children s executive function. Brain imaging technology can be incorporated into future research designs to investigate the underlying mechanisms of gymnastics impact on the brain structure and executive function in young children.

10.
Folia Neuropathol ; 61(3): 242-248, 2023.
Article in English | MEDLINE | ID: mdl-37818685

ABSTRACT

Involving in the immune response after cerebral infarction, astrocytes could secrete large amounts of pro- and anti-inflammatory factors. The aim of this study is to investigate the effect of Wnt3a intervention on the inflammatory response of oxygen-glucose deprivation (OGD) followed by reoxygenation (OGD/R) astrocyte model, and to provide a new target for immunoprotective treatment of cerebral infarction. We constructed the OGD/R rat astrocyte model, the astrocytes were treated by different concentrations of glucose (25, 50, 100 mM) intervened with/without Wnt3a (25 µg/ml). Microscope was used to observe the cell survival in rat astrocytes. The relative expression of inflammatory factors (TNF-a, IL-6, HIF-a) in rat astrocytes was detected by qRT-PCR. The expression of inflammatory factors such as TNF-a, IL-6 and HIF-a in rat astrocytes was increased after OGD/R treatment. The Wnt3a intervention promoted cell survival and decreased the expression of inflammatory factors in rat astrocytes induced by OGD/R. There is a neuroprotective effect that Wnt3a intervention could reduce inflammatory response in the OGD/R rat astrocyte model.


Subject(s)
Glucose , Oxygen , Rats , Animals , Glucose/metabolism , Oxygen/pharmacology , Oxygen/metabolism , Astrocytes/metabolism , Interleukin-6/metabolism , Interleukin-6/pharmacology , Cerebral Infarction/metabolism
11.
Carbohydr Polym ; 320: 121247, 2023 Nov 15.
Article in English | MEDLINE | ID: mdl-37659826

ABSTRACT

Although wet processes are promising for preparing cross-linked starch, they are currently challenged by lower cross-linking efficiency and the requirement of large amounts of salts. Herein, an efficient and greener wet process was proposed, in which the cross-linking performance between sodium hexametaphosphate (SHMP) and starch was enhanced with the aid of urea. The maximum degree of substitution (DS) of the urea-phosphorylated cross-linked starch (UPCS) was 0.040 at 35 °C, while that of the conventional phosphorylated cross-linked starch (CPCS) was 0.031 at 45 °C. Compared with CPCS, the maximum DS of UPCS was elevated by 29.03 %, but its optimum cross-linking temperature was reduced by 10 °C, indicating that the cross-linking efficiency of this novel wet process was greatly improved by urea. The structural difference between UPCS and CPCS was confirmed by using a series of techniques including 31P NMR and 13C NMR. Zeta potential results suggested that urea may promote starch cross-linking by preventing the closure of active sites through hydrophobic interactions. Due to the structural reinforcement of starch by urea, UPCS showed better thermal stability, water resistance, acid and alkali resistance, and steady shear tolerance properties. This study provides a facile wet process for the fabrication and application of cross-linked starch materials.

12.
J Hazard Mater ; 460: 132393, 2023 10 15.
Article in English | MEDLINE | ID: mdl-37660623

ABSTRACT

The widespread application of copper (Cu) -based fertilizers and pesticides could increase the accumulation of Cu in kiwifruit. According to a global survey, red- and yellow-fleshed kiwifruit contained more elevated amounts of Cu than green-fleshed kiwifruit due to weaker disease resistance and higher use of Cu pesticides. Intriguingly, our research revealed that external and endogenous ascorbic acid (AsA) reduced the phenotypic and physiological injury of Cu toxicity in kiwifruit. Cu stress assays and transcriptional analysis have shown that Cu treatment for 12 h significantly increased the AsA content in kiwifruit leaves and up-regulated key genes involved in AsA biosynthesis, such as GDP-L-galactose phosphorylase3 (GGP3) and GDP-mannose-3',5'-epimerase (GME). Overexpressing GGP3 in transgenic kiwifruit significantly increased the endogenous AsA content of kiwifruit, which was beneficial in mitigating Cu toxicity by decreasing levels of reactive oxygen species, malondialdehyde, and electrolyte leakage, as well as reducing damage to the chloroplast structure and photosystem II. This study presented a novel strategy to ameliorate plant Cu stress by increasing the endogenous antioxidant (AsA) content through transgenesis.


Subject(s)
Copper , Pesticides , Copper/toxicity , Ascorbic Acid/pharmacology , Biological Assay , Chloroplasts
13.
Ecol Evol ; 13(9): e10500, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37706160

ABSTRACT

Identifying conservation units is crucial for the effective conservation of threatened species. Previous cases are almost exclusively based on large-scale but coarse sampling for genetic structure analyses. Significant genetic structure can occur within a small range, and thus multiple conservation units may exist in narrowly distributed plants. However, small-scale genetic structure is often overlooked in conservation planning especially for wind-pollinated and wind-dispersed trees, largely due to the absence of dense and elaborate sampling. In this study, we focused on a representative endangered relict plant, Metasequoia glyptostroboides. Using both nuclear microsatellites (nSSRs) and chloroplast DNA (cpDNA) fragments, we sampled across the narrow distribution range of this species and determined its conservation units by exploring its genetic structure and historical demography. cpDNA haplotypes were classified into two groups, but mixed in space, suggesting that the existent wild trees of M. glyptostroboides cannot be divided into different evolutionarily significant units. However, using nSSRs, we detected strong spatial genetic structure, with significant genetic differentiation and weak gene flow between the samples in the east of the species' distribution range and other samples. The divergence between the two nSSR groups was dated to the Last Glacial Maximum (c. 19.6 kya), suggesting that such spatial genetic structure has been maintained for a long term. Therefore, these two nSSR groups should be considered as different conservation units, that is, management units, to protect intergroup genetic variations, which is likely to be the outputs of local adaptation. Our findings highlight the necessity to reveal small-scale genetic structure and population demography to improve the conservation strategies of evolutionary potential of endangered plants.

14.
J Org Chem ; 88(19): 13645-13654, 2023 Oct 06.
Article in English | MEDLINE | ID: mdl-37681260

ABSTRACT

A copper/PyBisulidine-catalyzed enantioselective alkynylation of electrophilic pyrazole-4,5-dione with terminal alkynes has been developed. Chiral tertiary propargylic alcohols bearing the pyrazolone motif were prepared with yields (up to 99%) and enantioselectivities (up to 99% ee). The prominent feature of this protocol includes its mild reaction conditions and good stereoselectivities. The nonlinear effect study showed that the catalytically active specie was a monomeric catalyst and that the excess copper activated the alkynes through the π-system.

15.
World J Clin Cases ; 11(22): 5193-5203, 2023 Aug 06.
Article in English | MEDLINE | ID: mdl-37621595

ABSTRACT

In recent years, because of the growing desire to improve the noninvasiveness and safety of tumor treatments, sonodynamic therapy has gradually become a popular research topic. However, due to the complexity of the therapeutic process, the relevant mechanisms have not yet been fully elucidated. One of the widely accepted possibilities involves the effect of reactive oxygen species. In this review, the mechanism of reactive oxygen species production by sonodynamic therapy (SDT) and ways to enhance the sonodynamic production of reactive oxygen species are reviewed. Then, the clinical application and limitations of SDT are discussed. In conclusion, current research on sonodynamic therapy should focus on the development of sonosensitizers that efficiently produce active oxygen, exhibit biological safety, and promote the clinical transformation of sonodynamic therapy.

16.
Nat Commun ; 14(1): 4987, 2023 08 17.
Article in English | MEDLINE | ID: mdl-37591884

ABSTRACT

PPARα corepressor NCoR1 is a key regulator of fatty acid ß-oxidation and ketogenesis. However, its regulatory mechanism is largely unknown. Here, we report that oncoprotein p21-activated kinase 4 (PAK4) is an NCoR1 kinase. Specifically, PAK4 phosphorylates NCoR1 at T1619/T2124, resulting in an increase in its nuclear localization and interaction with PPARα, thereby repressing the transcriptional activity of PPARα. We observe impaired ketogenesis and increases in PAK4 protein and NCoR1 phosphorylation levels in liver tissues of high fat diet-fed mice, NAFLD patients, and hepatocellular carcinoma patients. Forced overexpression of PAK4 in mice represses ketogenesis and thereby increases hepatic fat accumulation, whereas genetic ablation or pharmacological inhibition of PAK4 exhibites an opposite phenotype. Interestingly, PAK4 protein levels are significantly suppressed by fasting, largely through either cAMP/PKA- or Sirt1-mediated ubiquitination and proteasome degradation. In this way, our findings provide evidence for a PAK4-NCoR1/PPARα signaling pathway that regulates fatty acid ß-oxidation and ketogenesis.


Subject(s)
Fatty Acids , PPAR alpha , p21-Activated Kinases , Animals , Mice , Co-Repressor Proteins , Fatty Acids/metabolism , p21-Activated Kinases/genetics , PPAR alpha/genetics , Nuclear Receptor Co-Repressor 1/genetics , Humans , Phosphorylation , Signal Transduction
17.
Pak J Pharm Sci ; 36(3): 819-827, 2023 May.
Article in English | MEDLINE | ID: mdl-37580931

ABSTRACT

Gastric ulcer is a common gastrointestinal disease caused by excessive gastric acid secretion, which has been recognized as one of the most common causes of morbidity and mortality in the world. The skin of Rana chensinensis is rich in collagen and many previous studies have shown that it has certain bioactivity. Therefore, we extracted and purified collagen with a molecular weight less than 10000 Da from the skin of Rana chensinensis, and studied its gastric protective mechanism through the model of ethanol-induced gastric ulcer in Balb/c mice. The results showed that through macroscopic observation and significantly reduced ulcer index, it was proved that PCRCS could protect gastric mucosa and alleviate the damage of ethanol to gastric mucosa. PCRCS reduced ethanol-induced oxidative stress by boosting depleted SOD levels and dramatically lowering MDA levels, as well as significantly reducing lipid peroxidation. Additionally PCRCS (Protein Chinese Rana chesinensis Skin) additionally decreased the launch of inflammatory mediators TNF-α and IL-6 and more desirable the content material of protective elements NO and PGE2 in gastric mucosa. Based on these findings, we believe that PCRCS has potential stomach protective effects on ethanol-induced gastric ulcer, which may be achieved by inhibiting oxidative stress and stomach inflammation.


Subject(s)
Anti-Ulcer Agents , Gastric Mucosa , Ranidae , Stomach Ulcer , Animals , Mice , Anti-Ulcer Agents/adverse effects , Anti-Ulcer Agents/pharmacology , Anti-Ulcer Agents/therapeutic use , Collagen/pharmacology , Ethanol/toxicity , Gastric Mucosa/drug effects , Mice, Inbred BALB C , Stomach Ulcer/chemically induced , Stomach Ulcer/drug therapy , Stomach Ulcer/prevention & control , Protective Agents/adverse effects , Protective Agents/pharmacology , Protective Agents/therapeutic use , China , Disease Models, Animal , Skin
18.
Org Biomol Chem ; 21(30): 6225-6229, 2023 Aug 02.
Article in English | MEDLINE | ID: mdl-37482886

ABSTRACT

A Ni/PyBisulidine catalyzed asymmetric Michael addition of 3-acyloxy-2-oxindoles to nitroalkenes has been developed. Various quaternary substituted 3-acyloxy-2-oxindoles were obtained with excellent yields and diastereo- and enantioselectivities in a low-toxic green solvent, ethyl acetate, with a low catalyst loading (1 mol%). The reaction process is air and moisture tolerant. The substrate scope was also extended to α,ß-disubstituted nitroalkenes and 3-hydroxy-2-oxindoles, and good results were obtained.

19.
Zhongguo Zhong Yao Za Zhi ; 48(14): 3865-3873, 2023 Jul.
Article in Chinese | MEDLINE | ID: mdl-37475078

ABSTRACT

This study investigated the effect of guarana on plasma lipid metabolites in obese rats and analyzed its mechanism in the treatment of dyslipidemia in obesity. High-fat diet was used to establish obese rat models, and the therapeutic effect of guarana on obese rats was evaluated by measuring body weight, white fat, liver weight, and lipid content, as well as observing liver histomorphology. Lipid metabolites in plasma of rats in each group were detected by UHPLC-Q-TOF-MS lipidomics. The protein expressions of fatty acid synthase, acetyl-CoA carboxylase 1, triglyceride synthesis enzyme, carnitine palmitoyltransferase Ⅰ, and acetyl-coenzyme A acyltransferase 2 in rat liver were detected using Western blot. The results revealed that guarana significantly reduced body weight, white fat, and liver weight of obese rats due to high-fat diet, and alleviated dyslipidemia and liver steatosis. Lipidomics showed that some triglycerides and phospholipids were significantly elevated in the high-fat model group, and part of them was reduced after guarana treatment. Western blot found that guarana inhibited the expression of hepatic fatty acid and triglyceride synthesis-related proteins and increased the expression of fatty acid ß-oxidation-related proteins. Abnormalities in triglyceride and phospholipid metabolism are the main characteristics of plasma lipid metabolism in obese rats induced by high-fat diet. Guarana may regulate partial triglyceride and phospholipid metabolism by inhibiting hepatic fatty acid and triglyceride synthesis and increasing fatty acid ß-oxidation, thereby improving rat obesity and dyslipidemia.


Subject(s)
Dyslipidemias , Paullinia , Rats , Animals , Lipid Metabolism , Paullinia/metabolism , Lipidomics , Liver , Obesity/drug therapy , Obesity/genetics , Triglycerides , Fatty Acids , Phospholipids , Diet, High-Fat/adverse effects
20.
Acta Pharmacol Sin ; 44(10): 1962-1976, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37169852

ABSTRACT

Atherosclerosis is a major cause of death and disability in cardiovascular disease. Atherosclerosis associated with lipid accumulation and chronic inflammation leads to plaques formation in arterial walls and luminal stenosis in carotid arteries. Current approaches such as surgery or treatment with statins encounter big challenges in curing atherosclerosis plaque. The infiltration of proinflammatory M1 macrophages plays an essential role in the occurrence and development of atherosclerosis plaque. A recent study shows that TRIM24, an E3 ubiquitin ligase of a Trim family protein, acts as a valve to inhibit the polarization of anti-inflammatory M2 macrophages, and elimination of TRIM24 opens an avenue to achieve the M2 polarization. Proteolysis-targeting chimera (PROTAC) technology has emerged as a novel tool for the selective degradation of targeting proteins. But the low bioavailability and cell specificity of PROTAC reagents hinder their applications in treating atherosclerosis plaque. In this study we constructed a type of bioinspired PROTAC by coating the PROTAC degrader (dTRIM24)-loaded PLGA nanoparticles with M2 macrophage membrane (MELT) for atherosclerosis treatment. MELT was characterized by morphology, size, and stability. MELT displayed enhanced specificity to M1 macrophages as well as acidic-responsive release of dTRIM24. After intravenous administration, MELT showed significantly improved accumulation in atherosclerotic plaque of high fat and high cholesterol diet-fed atherosclerotic (ApoE-/-) mice through binding to M1 macrophages and inducing effective and precise TRIM24 degradation, thus resulting in the polarization of M2 macrophages, which led to great reduction of plaque formation. These results suggest that MELT can be considered a potential therapeutic agent for targeting atherosclerotic plaque and alleviating atherosclerosis progression, providing an effective strategy for targeted atherosclerosis therapy.


Subject(s)
Atherosclerosis , Plaque, Atherosclerotic , Proteolysis Targeting Chimera , Animals , Mice , Anti-Inflammatory Agents/therapeutic use , Atherosclerosis/drug therapy , Atherosclerosis/metabolism , Inflammation/drug therapy , Macrophages , Mice, Inbred C57BL , Plaque, Atherosclerotic/drug therapy , Plaque, Atherosclerotic/metabolism , Proteolysis Targeting Chimera/pharmacology , Proteolysis Targeting Chimera/therapeutic use , Polylactic Acid-Polyglycolic Acid Copolymer/pharmacology , Nanoparticles/therapeutic use
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