Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 260
Filter
1.
Subst Abuse Treat Prev Policy ; 19(1): 34, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38978076

ABSTRACT

BACKGROUND: Evaluating the risk of relapse is a pivotal step in the treatment of patients with methamphetamine use disorder (MUD). The 30-item Stimulant Relapse Risk Scale (SRRS) was originally developed in Japan to meet the demand. This study examined the reliability, validity, and factor structure of the Chinese version of the SRRS for patients with MUD. METHODS: 247 patients with MUD self-rated the Chinese version of the SRRS. Cronbach's alpha coefficients and inter-item correlation analysis were used to assess the internal consistency reliability. Construct validity was determined through confirmatory factor analysis (CFA), and concurrent validity was examined using the visual analogue scale (VAS) for drug craving and the severity of dependence scale (SDS). We followed the participants for 1 year and assessed the predictive validity based on the correlation of the scores of the Chinese version of the SRRS with the relapse rate within 3, 6, and 12 months of follow-up. RESULTS: CFA revealed satisfactory model fit estimates for the 22-item Chinese version of the SRRS that consisted of four subscales. The four-factored 22-item Chinese version of the SRRS had adequate internal consistency with Cronbach's alphas ranging from 0.76 to 0.92. The 22-item Chinese version of the SRRS scores were significantly correlated with the VAS and SDS scores as well as the relapse rate within 3, 6, and 12 months, indicating good concurrent and predictive validity of this scale. The receiver operating characteristic curve revealed a cutoff score of 40 could discriminate between participants with (SDS score ≥ 4) and without (SDS score < 4) methamphetamine dependence (area under the curve = 0.71, p < 0.01). CONCLUSIONS: The 22-item Chinese version of the SRRS that consists of four subscales is a valid and reliable instrument to assess the relapse risk in patients with MUD.


Subject(s)
Amphetamine-Related Disorders , Methamphetamine , Psychometrics , Recurrence , Humans , Male , Amphetamine-Related Disorders/diagnosis , Amphetamine-Related Disorders/psychology , Female , Adult , Reproducibility of Results , Risk Assessment , Middle Aged , China , Factor Analysis, Statistical , Young Adult
3.
iScience ; 27(4): 109297, 2024 Apr 19.
Article in English | MEDLINE | ID: mdl-38715943

ABSTRACT

The One Health (OH) approach is used to control/prevent zoonotic events. However, there is a lack of tools for systematically assessing OH practices. Here, we applied the Global OH Index (GOHI) to evaluate the global OH performance for zoonoses (GOHI-Zoonoses). The fuzzy analytic hierarchy process algorithm and fuzzy comparison matrix were used to calculate the weights and scores of five key indicators, 16 subindicators, and 31 datasets for 160 countries and territories worldwide. The distribution of GOHI-Zoonoses scores varies significantly across countries and regions, reflecting the strengths and weaknesses in controlling or responding to zoonotic threats. Correlation analyses revealed that the GOHI-Zoonoses score was associated with economic, sociodemographic, environmental, climatic, and zoological factors. Additionally, the Human Development Index had a positive effect on the score. This study provides an evidence-based reference and guidance for global, regional, and country-level efforts to optimize the health of people, animals, and the environment.

4.
Microbes Infect ; 26(5-6): 105350, 2024.
Article in English | MEDLINE | ID: mdl-38723999

ABSTRACT

The widespread transmission of SARS-CoV-2 in humans poses a serious threat to public health security, and a growing number of studies have discovered that SARS-CoV-2 infection in wildlife and mutate over time. This article mainly reports the first systematic review and meta-analysis of the prevalence of SARS-CoV-2 in wildlife. The pooled prevalence of the 29 included articles was calculated by us using a random effects model (22.9%) with a high heterogeneity (I2 = 98.7%, p = 0.00). Subgroup analysis and univariate regression analysis found potential risk factors contributing to heterogeneity were country, wildlife species, sample type, longitude, and precipitation. In addition, the prevalence of SARS-CoV-2 in wildlife increased gradually over time. Consequently, it is necessary to comprehensively analyze the risk factors of SARS-CoV-2 infection in wildlife and develop effective control policies, as well as to monitor the mutation of SARS-CoV-2 in wildlife at all times to reduce the risk of SARS-CoV-2 transmission among different species.


Subject(s)
Animals, Wild , COVID-19 , SARS-CoV-2 , COVID-19/epidemiology , COVID-19/transmission , COVID-19/virology , Animals , Animals, Wild/virology , Prevalence , Humans , Risk Factors
5.
Infect Dis Model ; 9(2): 618-633, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38645696

ABSTRACT

The rapid acceleration of global warming has led to an increased burden of high temperature-related diseases (HTDs), highlighting the need for advanced evidence-based management strategies. We have developed a conceptual framework aimed at alleviating the global burden of HTDs, grounded in the One Health concept. This framework refines the impact pathway and establishes systematic data-driven models to inform the adoption of evidence-based decision-making, tailored to distinct contexts. We collected extensive national-level data from authoritative public databases for the years 2010-2019. The burdens of five categories of disease causes - cardiovascular diseases, infectious respiratory diseases, injuries, metabolic diseases, and non-infectious respiratory diseases - were designated as intermediate outcome variables. The cumulative burden of these five categories, referred to as the total HTD burden, was the final outcome variable. We evaluated the predictive performance of eight models and subsequently introduced twelve intervention measures, allowing us to explore optimal decision-making strategies and assess their corresponding contributions. Our model selection results demonstrated the superior performance of the Graph Neural Network (GNN) model across various metrics. Utilizing simulations driven by the GNN model, we identified a set of optimal intervention strategies for reducing disease burden, specifically tailored to the seven major regions: East Asia and Pacific, Europe and Central Asia, Latin America and the Caribbean, Middle East and North Africa, North America, South Asia, and Sub-Saharan Africa. Sectoral mitigation and adaptation measures, acting upon our categories of Infrastructure & Community, Ecosystem Resilience, and Health System Capacity, exhibited particularly strong performance for various regions and diseases. Seven out of twelve interventions were included in the optimal intervention package for each region, including raising low-carbon energy use, increasing energy intensity, improving livestock feed, expanding basic health care delivery coverage, enhancing health financing, addressing air pollution, and improving road infrastructure. The outcome of this study is a global decision-making tool, offering a systematic methodology for policymakers to develop targeted intervention strategies to address the increasingly severe challenge of HTDs in the context of global warming.

6.
AIDS Behav ; 28(7): 2183-2192, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38625625

ABSTRACT

Vaccine hesitancy is one of the top 10 threats to global health, which affects the prevalence and fatality of vaccine-preventable diseases over the world. During the COVID-19 pandemic, people living with HIV (PLWH) may have higher risks of infection, more serious complications, and worse prognosis without the protection of the COVID-19 vaccine. A systematic review and meta-analysis aiming to evaluate the prevalence of COVID-19 vaccine hesitancy among PLWH was conducted using PubMed, Embase, and Web of Science databases for studies published between January 1, 2020, and August 31, 2022. The pooled prevalence with a corresponding 95%CI of COVID-19 vaccine hesitancy among PLWH was reported. Subgroup analysis was conducted to explore variation in prevalence across different categories. 23 studies with a total of 19,922 PLWH were included in this study. The prevalence of COVID-19 vaccine hesitancy among PLWH was 34.0%, and the influencing factors included male, influenza vaccination experience, and a CD4 count of more than 200 cells/mm3. Subgroup analysis did not identify significant causes of heterogeneity but showed that the prevalence of COVID-19 vaccine hesitancy among PLWH varies by study period, region, and race. Although all PLWH are recommended to receive the COVID-19 vaccine, a large proportion of them remain hesitant to be vaccinated. Therefore, governments and relevant institutions should take specific measures to encourage and promote vaccination to improve the coverage of the COVID-19 vaccine among PLWH.


Subject(s)
COVID-19 Vaccines , COVID-19 , HIV Infections , SARS-CoV-2 , Vaccination Hesitancy , Female , Humans , Male , COVID-19/prevention & control , COVID-19/epidemiology , COVID-19/psychology , COVID-19 Vaccines/administration & dosage , HIV Infections/psychology , HIV Infections/epidemiology , HIV Infections/prevention & control , Vaccination/psychology , Vaccination/statistics & numerical data , Vaccination Hesitancy/psychology , Vaccination Hesitancy/statistics & numerical data
7.
J Nat Prod ; 87(5): 1416-1425, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38687902

ABSTRACT

In nature, proanthocyanidins (PACs) with A-type linkages are relatively rare, likely due to biosynthetic constraints in the formation of additional ether bonds to be introduced into the more common B-type precursors. However, A-type linkages confer greater structural rigidity on PACs than do B-type linkages. Prior investigations into the structure-activity relationships (SAR) describing how plant-derived PACs with B- and complex AB-type linkages affect their capacity for dentin biomodification indicate that a higher ratio of double linkages leads to a greater interaction with dentin type I collagen. Thus, A-type PACs emerge as particularly intriguing candidates for interventional functional biomaterials. This study employed a free-radical-mediated oxidation using DPPH to transform trimeric and tetrameric B-type PACs, 2 and 4, respectively, into their exclusively A-type linked analogues, 3 and 5, respectively. The structures and absolute configurations of the semisynthetic products, including the new all-A-type tetramer 5, were determined by comprehensive spectroscopic analysis. Additionally, molecular modeling investigated the conformational characteristics of all trimers and tetramers, 1-5. Our findings suggest that the specific interflavan linkages significantly impact the flexibility and low-energy conformations of the connected monomeric units, which conversely can affect the bioactive conformations relevant for dentin biomodification.


Subject(s)
Proanthocyanidins , Proanthocyanidins/chemistry , Molecular Structure , Structure-Activity Relationship
8.
J Agric Food Chem ; 72(17): 9746-9754, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38602331

ABSTRACT

The latex of Euphorbia peplus and its major component 20-deoxyingenol-3-angelate (DI3A) displayed significant nematicidal activity against Caenorhabditis elegans and Panagrellus redivivus. DI3A treatment inhibited the growth and development of nematodes and caused significantly negative effects on locomotion behavior, reproduction, and accumulation of reactive oxygen species. Transcriptome analysis indicated that differential expression genes in DI3A-treated C. elegans were mainly associated with the metabolism, growth, and development process, which were further confirmed by RT-qPCR experiments. The expression level of TPA-1 gene encoding a protein kinase C isotype was obviously upregulated by DI3A treatment, and knockdown of TPA-1 by RNAi technology in the nematode could relieve the growth-inhibitory effect of DI3A. Metabolic analysis indicated that DI3A was hardly metabolized by C. elegans, but a glycosylated indole derivative was specifically accumulated likely due to the activation of detoxification. Overall, our findings suggested that DI3A from E. peplus latex exerted a potent nematicidal effect through the gene TPA-1, which provides a potential target for the control of nematodes and also suggests the potential application value of E. peplus latex and DI3A as botanical nematicides.


Subject(s)
Antinematodal Agents , Caenorhabditis elegans , Euphorbia , Latex , Protein Kinase C , Animals , Caenorhabditis elegans/drug effects , Caenorhabditis elegans/genetics , Caenorhabditis elegans/enzymology , Caenorhabditis elegans/metabolism , Caenorhabditis elegans/growth & development , Latex/chemistry , Latex/metabolism , Antinematodal Agents/pharmacology , Antinematodal Agents/chemistry , Antinematodal Agents/metabolism , Euphorbia/chemistry , Protein Kinase C/metabolism , Protein Kinase C/genetics , Plant Extracts/pharmacology , Plant Extracts/chemistry
9.
J Cardiovasc Pharmacol ; 84(1): 118-123, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38547516

ABSTRACT

ABSTRACT: This study seeks to identify the anticoagulant efficacy of rivaroxaban treatment on thrombi detected using echocardiography of the left atrial appendage in 275 patients with persistent atrial fibrillation. During follow-up after 9-24 weeks of rivaroxaban treatment, patients were divided into "effective group" (n = 143) and "ineffective group" (n = 132) according to the thrombolytic effect of the drug. Left atrial diameter (LAD), left atrial ejection fraction (LAEF), left ventricular ejection fraction (LVEF), mean diameter of left atrial appendage (LAAD mean ), angle between left atrial appendage and left atrium (LAA-A), velocity of blood flow in left atrial appendage (LAA-v), and thrombus size were compared before and after drug administration. Following treatment, LAEF, LVEF, and LAA-v values were greater and LAD and LAAD mean values were lower in the effective ( P < 0.05). Logistic regression analysis showed significant correlations of LAD, LAEF, LVEF, LAA-A, and LAA-v with anticoagulant efficacy ( P < 0.05). The efficacy of rivaroxaban in treatment of left atrial auricular thrombosis in patients with persistent AF was correlated with LAD, LAEF, LVEF, LAA-A, and LAA-v. Multivariate logistic regression analysis further revealed LAEF [odds ratio (OR) 1.7, 95% confidence interval (CI), 0.45-16.9, P = 0.008], 3D-EF (OR 6.4, 95% CI, 1.06-16.9, P = 0.039) and left ventricular global longitudinal strain (OR 18.0, 95% CI, 1.38-35.68, P = 0.028) as factors related to left atrial appendage thrombus. Echocardiography with global longitudinal strain assessment could be effectively utilized to evaluate the functional parameters of LAA and thus aid in predicting the safety of rivaroxaban as an anticoagulation agent.


Subject(s)
Atrial Appendage , Atrial Fibrillation , Echocardiography, Three-Dimensional , Factor Xa Inhibitors , Rivaroxaban , Humans , Atrial Fibrillation/drug therapy , Atrial Fibrillation/physiopathology , Atrial Fibrillation/diagnostic imaging , Atrial Fibrillation/diagnosis , Female , Male , Rivaroxaban/therapeutic use , Rivaroxaban/administration & dosage , Aged , Middle Aged , Treatment Outcome , Atrial Appendage/diagnostic imaging , Atrial Appendage/physiopathology , Atrial Appendage/drug effects , Factor Xa Inhibitors/adverse effects , Factor Xa Inhibitors/therapeutic use , Thrombosis/diagnostic imaging , Thrombosis/drug therapy , Thrombosis/physiopathology , Predictive Value of Tests , Atrial Function, Left/drug effects , Thrombolytic Therapy , Ventricular Function, Left/drug effects , Time Factors
10.
Zhongguo Zhong Yao Za Zhi ; 49(2): 498-508, 2024 Jan.
Article in Chinese | MEDLINE | ID: mdl-38403325

ABSTRACT

To fully understand whether Saposhnikoviae Radix polysaccharides(SP) can be metabolized in gastric fluid and the meta-bolic behavior, this study systematically analyzed the metabolites in simulated gastric fluid of SP by high-performance liquid chromatography-ion trap time-of-flight mass spectrometry(HPLC-IT-TOF-MS) technology in combination with zebrafish immune activity evaluation. Based on the obtained accurate relative molecular mass, chromatographic retention behavior, MS fragmentation patterns, refe-rence standards, and relevant literature reports, 19 metabolites were analyzed and identified. Among them, five monosaccharides and 14 oligosaccharides were generated as metabolites. Several reducing sugars, including mannose, glucose, rhamnose, and xylose, were accurately identified in the gastric fluid metabolites. Zebrafish pharmacological evaluation results indicated that SP maintained good immune activity after gastric fluid metabolism, with the most significant increase in immune cell density observed at W3(simulated gastric fluid metabolism for 2 hours). Among the gastric fluid metabolites, M1 and M3(Hex-Hex-Man) may be most closely related to pharmacological activity and could be further studied as potential active fragments.


Subject(s)
Drugs, Chinese Herbal , Zebrafish , Humans , Animals , Chromatography, High Pressure Liquid/methods , Plant Roots/chemistry , Polysaccharides/analysis , Drugs, Chinese Herbal/chemistry
11.
Int Immunopharmacol ; 130: 111710, 2024 Mar 30.
Article in English | MEDLINE | ID: mdl-38394888

ABSTRACT

Influenza virus is a kind of virus that poses several hazards of animal and human health. Therefore, it is important to develop an effective vaccine to prevent influenza. To this end we successfully packaged recombinant adenovirus rAd-NP-M2e-GFP expressing multiple copies of influenza virus conserved antigens NP and M2e and packaged empty vector adenovirus rAd-GFP. The effect of rAd-NP-M2e-GFP on the activation of dendritic cell (DC) in vitro and in vivo was detected by intranasal immunization. The results showed that rAd-NP-M2e-GFP promoted the activation of DC in vitro and in vivo. After the primary immunization and booster immunization of mice through the nasal immune way, the results showed that rAd-NP-M2e-GFP induced enhanced local mucosal-specific T cell responses, increased the content of SIgA in broncho alveolar lavage fluids (BALF) and triggered the differentiation of B cells in the germinal center. It is proved that rAd-NP-M2e-GFP can significantly elicit mucosal immunity and systemic immune response. In addition, rAd-NP-M2e-GFP could effectively protect mice after H1N1 influenza virus challenge. To lay the foundation and provide reference for further development of influenza virus mucosal vaccine in the future.


Subject(s)
Adenovirus Vaccines , Influenza A Virus, H1N1 Subtype , Influenza Vaccines , Orthomyxoviridae Infections , Animals , Mice , Humans , Adenoviridae/genetics , Immunization , Vaccines, Synthetic , Immunity, Mucosal , Mice, Inbred BALB C , Antibodies, Viral
13.
Acta Pharmacol Sin ; 45(6): 1142-1159, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38409216

ABSTRACT

Alzheimer's disease (AD), a progressive neurodegenerative disorder, is the most common cause of dementia in elderly people and substantially affects patient quality of life. Oxidative stress is considered a key factor in the development of AD. Nrf2 plays a vital role in maintaining redox homeostasis and regulating neuroinflammatory responses in AD. Previous studies show that potassium 2-(1-hydroxypentyl)-benzoate (PHPB) exerts neuroprotective effects against cognitive impairment in a variety of dementia animal models such as APP/PS1 transgenic mice. In this study we investigated whether PHPB ameriorated the progression of AD by reducing oxidative stress (OS) damage. Both 5- and 13-month-old APP/PS1 mice were administered PHPB (100 mg·kg-1·d-1, i.g.) for 10 weeks. After the cognition assessment, the mice were euthanized, and the left hemisphere of the brain was harvested for analyses. We showed that 5-month-old APP/PS1 mice already exhibited impaired performance in the step-down test, and knockdown of Nrf2 gene only slightly increased the impairment, while knockdown of Nrf2 gene in 13-month-old APP/PS1 mice resulted in greatly worse performance. PHPB administration significantly ameliorated the cognition impairments and enhanced antioxidative capacity in APP/PS1 mice. In addition, PHPB administration significantly increased the p-AKT/AKT and p-GSK3ß/GSK3ß ratios and the expression levels of Nrf2, HO-1 and NQO-1 in APP/PS1 mice, but these changes were abolished by knockdown of Nrf2 gene. In SK-N-SH APPwt cells and primary mouse neurons, PHPB (10 µM) significantly increased the p-AKT/AKT and p-GSK3ß/GSK3ß ratios and the level of Nrf2, which were blocked by knockdown of Nrf2 gene. In summary, this study demonstrates that PHPB exerts a protective effect via the Akt/GSK3ß/Nrf2 pathway and it might be a promising neuroprotective agent for the treatment of AD.


Subject(s)
Alzheimer Disease , Disease Models, Animal , Memory Disorders , Mice, Transgenic , NF-E2-Related Factor 2 , Oxidative Stress , Signal Transduction , Animals , NF-E2-Related Factor 2/metabolism , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Oxidative Stress/drug effects , Signal Transduction/drug effects , Mice , Memory Disorders/drug therapy , Memory Disorders/metabolism , Neuroprotective Agents/pharmacology , Neuroprotective Agents/therapeutic use , Male , Humans , Mice, Inbred C57BL
14.
J Affect Disord ; 348: 70-77, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38065482

ABSTRACT

BACKGROUND: China has experienced a surge period of COVID-19 pandemic since December 2022. Healthcare workers (HCWs) were exposed to huge workload under high risk of being infected, and significant levels of trauma, which might cause Post-traumatic Stress Disorders (PTSD) symptoms in HCWs. OBJECTIVES: To identify the prevalence of PTSD symptoms among HCWs in the Chinese mainland during the surge period of the COVID-19 pandemic; to explore their psycho-social factors of PTSD symptoms. METHODS: A multicenter cross-sectional study was conducted among HCWs in Chinese mainland from January 5 to February 9, 2023, covering seven geographical regions. 6552 participants were recruited by convenience sampling. Data were collected on demographic characteristics, work-related factors, and psychological factors by online questionnaires. Univariate analysis and binary logistic regression were used to determine the influencing factors of PTSD symptoms. RESULTS: The prevalence of PTSD symptoms among HCWs was 37.49 %. A higher level of mindfulness, resilience, and perceived social support were protective factors. Female gender, nurses, higher educational attainment, married status, more working years, higher perceived risk of contracting COVID-19 due to work, and higher perceived work intensity were risk factors. CONCLUSION: High prevalence of PTSD symptoms among HCWs necessitates psychological interventions. Tailored interventions, designed by professional psychiatrists, should be tailored to address the stressors. A comprehensive approach, incorporating mindfulness, resilience-building, and perceived social support enhancement, is vital to bolster the mental well-being of HCWs exposed to traumatic events, thus mitigating the impact of PTSD effectively. Additionally, it is essential to provide support to HCWs with other potential risk factors.


Subject(s)
COVID-19 , Stress Disorders, Post-Traumatic , Humans , Female , Cross-Sectional Studies , COVID-19/epidemiology , Prevalence , Stress Disorders, Post-Traumatic/epidemiology , Pandemics , China/epidemiology , Health Personnel
15.
J Biomed Mater Res B Appl Biomater ; 112(1): e35333, 2024 01.
Article in English | MEDLINE | ID: mdl-37792302

ABSTRACT

Flavan-3-ol monomers are the building blocks of proanthocyanidins (PACs), natural compounds from plants shown to mediate specific biologic activities on dentin. While the stereochemistry of the terminal flavan-3-ols, catechin (C) versus epicatechin (EC), impacts the biomechanical properties of the dentin matrix treated with oligomeric PACs, structure-activity relationships driving this bioactivity remain elusive. To gain insights into the modulatory role of the terminal monomers, two highly congruent trimeric PACs from Pinus massoniana only differing in the stereochemistry of the terminal unit (Trimer-C vs. Trimer-EC) were prepared to evaluate their chemical characteristics as well as their effects on the viscoelasticity and biostability of biomodified dentin matrices via infrared spectroscopy and multi-scale dynamic mechanical analyses. The subtle alteration of C versus EC as terminal monomers lead to distinct immediate PAC-trimer biomodulation of the dentin matrix. Nano- and micro-dynamic mechanical analyses revealed that Trimer-EC increased the complex moduli (0.51 GPa) of dentin matrix more strongly than Trimer-C (0.26 GPa) at the nanoscale length (p < 0.001), whereas the reverse was found at the microscale length (p < .001). The damping capacity (tan δ) of dentin matrix decreased by 70% after PAC treatment at the nano-length scale, while increased values were found at the micro-length scale (~0.24) compared to the control (0.18 ; p < .001). An increase in amide band intensities and a decrease of complex moduli was observed after storage in simulated body fluid for both Trimer-C and Trimer-EC modified dentin. The stereochemical configuration of the terminal monomeric units, C and EC, did not impact the chemo-mechanical stability of dentin matrix.


Subject(s)
Catechin , Proanthocyanidins , Flavonoids/pharmacology , Flavonoids/analysis , Proanthocyanidins/pharmacology , Proanthocyanidins/analysis , Proanthocyanidins/chemistry , Catechin/pharmacology , Dentin/chemistry
16.
Acta Pharmacol Sin ; 45(2): 248-267, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37833536

ABSTRACT

There are few effective and safe neuroprotective agents for the treatment of ischemic stroke currently. Caffeic acid is a phenolic acid that widely exists in a number of plant species. Previous studies show that caffeic acid ameliorates brain injury in rats after cerebral ischemia/reperfusion. In this study we explored the protective mechanisms of caffeic acid against oxidative stress and ferroptosis in permanent cerebral ischemia. Ischemia stroke was induced on rats by permanent middle cerebral artery occlusion (pMCAO). Caffeic acid (0.4, 2, 10 mg·kg-1·d-1, i.g.) was administered to the rats for 3 consecutive days before or after the surgery. We showed that either pre-pMCAO or post-pMCAO administration of caffeic acid (2 mg·kg-1·d-1) effectively reduced the infarct volume and improved neurological outcome. The therapeutic time window could last to 2 h after pMCAO. We found that caffeic acid administration significantly reduced oxidative damage as well as neuroinflammation, and enhanced antioxidant capacity in pMCAO rat brain. We further demonstrated that caffeic acid down-regulated TFR1 and ACSL4, and up-regulated glutathione production through Nrf2 signaling pathway to resist ferroptosis in pMCAO rat brain and in oxygen glucose deprivation/reoxygenation (OGD/R)-treated SK-N-SH cells in vitro. Application of ML385, an Nrf2 inhibitor, blocked the neuroprotective effects of caffeic acid in both in vivo and in vitro models, evidenced by excessive accumulation of iron ions and inactivation of the ferroptosis defense system. In conclusion, caffeic acid inhibits oxidative stress-mediated neuronal death in pMCAO rat brain by regulating ferroptosis via Nrf2 signaling pathway. Caffeic acid might serve as a potential treatment to relieve brain injury after cerebral ischemia. Caffeic acid significantly attenuated cerebral ischemic injury and resisted ferroptosis both in vivo and in vitro. The regulation of Nrf2 by caffeic acid initiated the transcription of downstream target genes, which were shown to be anti-inflammatory, antioxidative and antiferroptotic. The effects of caffeic acid on neuroinflammation and ferroptosis in cerebral ischemia were explored in a primary microglia-neuron coculture system. Caffeic acid played a role in reducing neuroinflammation and resisting ferroptosis through the Nrf2 signaling pathway, which further suggested that caffeic acid might be a potential therapeutic method for alleviating brain injury after cerebral ischemia.


Subject(s)
Brain Injuries , Brain Ischemia , Caffeic Acids , Ferroptosis , Neuroprotective Agents , Reperfusion Injury , Rats , Animals , Rats, Sprague-Dawley , NF-E2-Related Factor 2/metabolism , Neuroinflammatory Diseases , Signal Transduction , Brain Ischemia/drug therapy , Brain Ischemia/metabolism , Infarction, Middle Cerebral Artery/drug therapy , Infarction, Middle Cerebral Artery/metabolism , Brain Injuries/drug therapy , Neuroprotective Agents/pharmacology , Neuroprotective Agents/therapeutic use , Antioxidants/pharmacology , Reperfusion Injury/metabolism
17.
Chinese Pharmacological Bulletin ; (12): 201-207, 2024.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1013588

ABSTRACT

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting both upper and lower motor neurons. ALS patients develop progressive muscle atrophy, muscle weak and paralysis, finally died of respiratory failure. ALS is characterized by fast aggression and high mortality. What' s more, the disease is highly heterogeneous with unclear pathogenesis and lacks effective drugs for therapy. In this review, we summarize the main pathological mechanisms and the current drugs under development for ALS, which may provide a reference for the drug discovery in the future.

18.
Eur J Med Res ; 28(1): 591, 2023 Dec 15.
Article in English | MEDLINE | ID: mdl-38102653

ABSTRACT

BACKGROUND: Although great progress has been made in anti-cancer therapy, the prognosis of laryngeal squamous cell carcinoma (LSCC) patients remains unsatisfied. Quantities of studies demonstrate that glycolytic reprograming is essential for the progression of cancers, where triosephosphate isomerase 1 (TPI1) serves as a catalytic enzyme. However, the clinicopathological significance and potential biological functions of TPI1 underlying LSCC remains obscure. METHODS: We collected in-house 82 LSCC tissue specimens and 56 non-tumor tissue specimens. Tissue microarrays (TMA) and immunohistochemical (IHC) experiments were performed. External LSCC microarrays and bulk RNA sequencing data were integrated to evaluate the expression of TPI1. We used a log-rank test and the CIBERSORT algorithm to assess the prognostic value of TPI1 and its association with the LSCC microenvironment. Malignant laryngeal epithelial cells and immune-stromal cells were identified using inferCNV and CellTypist. We conducted a comprehensive analysis to elucidate the molecular functions of TPI1 in LSCC tissue and single cells using Pearson correlation analysis, high dimensional weighted gene co-expression analysis, gene set enrichment analysis, and clustered regularly interspaced short palindromic repeats (CRISPR) screen. We explored intercellular communication patterns between LSCC single cells and immune-stromal cells and predicted several therapeutic agents targeting TPI1. RESULTS: Based on the in-house TMA and IHC analysis, TPI1 protein was found to have a strong positive expression in the nucleus of LSCC cells but only weakly positive activity in the cytoplasm of normal laryngeal cells (p < 0.0001). Further confirmation of elevated TPI1 mRNA expression was obtained from external datasets, comparing 251 LSCC tissue samples to 136 non-LSCC tissue samples (standardized mean difference = 1.06). The upregulated TPI1 mRNA demonstrated a high discriminative ability between LSCC and non-LSCC tissue (area under the curve = 0.91; sensitivity = 0.87; specificity = 0.79), suggesting its potential as a predictive marker for poor prognosis (p = 0.037). Lower infiltration abundance was found for plasma cells, naïve B cells, monocytes, and neutrophils in TPI-high expression LSCC tissue. Glycolysis and cell cycle were significantly enriched pathways for both LSCC tissue and single cells, where heat shock protein family B member 1, TPI1, and enolase 1 occupied a central position. Four outgoing communication patterns and two incoming communication patterns were identified from the intercellular communication networks. TPI1 was predicted as an oncogene in LSCC, with CRISPR scores less than -1 across 71.43% of the LSCC cell lines. TPI1 was positively correlated with the half maximal inhibitory concentration of gemcitabine and cladribine. CONCLUSIONS: TPI1 is dramatically overexpressed in LSCC than in normal tissue, and the high expression of TPI1 may promote LSCC deterioration through its metabolic and non-metabolic functions. This study contributes to advancing our knowledge of LSCC pathogenesis and may have implications for the development of targeted therapies in the future.


Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Laryngeal Neoplasms , Humans , Squamous Cell Carcinoma of Head and Neck/genetics , RNA/genetics , Triose-Phosphate Isomerase/genetics , Triose-Phosphate Isomerase/metabolism , Immunohistochemistry , Laryngeal Neoplasms/genetics , Laryngeal Neoplasms/metabolism , Laryngeal Neoplasms/pathology , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/pathology , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Prognosis , RNA, Messenger/genetics , Head and Neck Neoplasms/genetics , Gene Expression Regulation, Neoplastic , Tumor Microenvironment
19.
J Nat Prod ; 86(11): 2468-2473, 2023 11 24.
Article in English | MEDLINE | ID: mdl-37939268

ABSTRACT

Three unusual sesterterpenoids featuring unprecedented rearranged colquhounane (C25) and tetranorcolquhounane (C21) frameworks, colquhounoids E (1) and F (3) and norcolquhounoid F (2), were isolated from a Lamiaceae medicinal plant Colquhounia coccinea var. mollis. Their structures were elucidated by spectroscopic analysis and quantum chemical calculations. A biomimetic inspired regioselective cyclopropane cleavage was achieved under acidic conditions. The immunosuppressive activities of these new sesterterpenoids were also evaluated.


Subject(s)
Lamiaceae , Plants, Medicinal , Spectrum Analysis , Lamiaceae/chemistry , Molecular Structure
20.
Clin Exp Optom ; : 1-8, 2023 Nov 08.
Article in English | MEDLINE | ID: mdl-37939715

ABSTRACT

CLINICAL RELEVANCE: The morphological characteristics of the optic nerve head (ONH) in myopic eyes are a clinically significant issue, especially for high myopia in school-aged children, and this can be monitored using optical coherence tomography. BACKGROUND: The purpose of this study is to investigate the morphological characteristics of ONH, and the factors associated with peripapillary choroidal thickness in Chinese school-aged high myopia children. METHODS: A total of 48 patients, possessing 48 high myopia eyes and 48 contralateral low myopia eyes were enrolled. The ONH characteristic parameters, including peripapillary retinal nerve fibre layer thickness, peripapillary choroidal thickness, peripapillary choroidal blood flow density, Bruch's membrane opening (BMO) characteristic parameters were measured on optical coherence tomography scans. RESULTS: Eyes with high myopia had a larger disc size, higher peripapillary atrophy area proportion, larger peripapillary atrophy area, larger BMO minimum rim width, lower peripapillary choroidal thickness compared with those contralateral low myopia eyes (all P < 0.001). The BMO distance and border length were longer, and border tissue angle was smaller in the high myopia eyes. The multivariate regression analysis revealed that border length, axial length, and border tissue angle were independently associated with peripapillary choroidal thickness (all P < 0.05); axial length was associated with peripapillary retinal nerve fibre layer thickness (P = 0.007). CONCLUSION: The peripapillary atrophy area, BMO area, border length, BMO distance, and BMO minimum rim width increased, but peripapillary choroidal thickness, retinal nerve fibre layer thickness decreased with axial elongation of the globe in young myopia children. Longer axial length and border length were positively correlated with lower peripapillary choroidal thickness, and a smaller border tissue angle was positively correlated with lower peripapillary choroidal thickness were found in this study. Monitoring of border length and border tissue angle is essential in the early stages of myopia in children.

SELECTION OF CITATIONS
SEARCH DETAIL
...