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1.
Org Biomol Chem ; 2024 Sep 10.
Article in English | MEDLINE | ID: mdl-39254473

ABSTRACT

A photocatalytic decarboxylative aminoalkylation of 4-cyanopyridines with N-arylglycines is achieved, providing 4-(aminomethyl)pyridine derivatives in moderate to good yields. This organic photocatalytic reaction undergoes a radical-radical cross-coupling process under redox-neutral conditions, featuring simple operation, readily available N-arylglycines and a broad substrate scope. Mechanistic investigations indicated that a proton-coupled electron-transfer process was involved to enable the single electron transfer between the reduced photocatalyst and 4-cyanopyridine in the presence of N-arylglycines.

2.
J Appl Clin Med Phys ; : e14508, 2024 Sep 06.
Article in English | MEDLINE | ID: mdl-39243112

ABSTRACT

PURPOSE: The goal of this study is to assess the utility of Cherenkov imaging (CI) and scintillation imaging (SI) as high-resolution techniques to measure CyberKnife® beam shape quantitatively at the irradiation surface in quality assurance (QA). METHODS: The EMCCD camera captured scintillation and Cherenkov photons arising from 6 MV x-ray dose deposition produced by the CyberKnife® VSI System. Two imaging methods were done at source to surface distance of 800 cm with the same field size, ranging from 10 to 60 mm using fixed cones and iris collimators. The output sensitivity and constancy were measured using the SI and CI, and benchmarked against an ionization chamber. Line profiles of each beam measured by optical imaging were compared with film measurement. Position shifts were introduced to test the sensitivity of SI and CI to small beam position deviations. To assess reproducibility, the beam measurements were tested three times on 5 consecutive days. RESULTS: Both systems exhibited comparable sensitivity to the ionization chamber in response to fluctuations in CyberKnife® output. The beam profiles in SI matched well with the measured film image, with accuracy in the range of ± 0.20 and ± 0.26 mm standard deviation for the circle and iris field, respectively. The corresponding accuracy measured by CI is in the range of ± 0.25 and ± 0.33 mm, respectively. These are all within the tolerance recommended by the guidelines of CyberKnife® QA. The accuracy measured by SI and CI for 1 mm beam position shift within 0.21 and 0.45 mm tolerance, respectively. Repeatability measurements of the beam have shown a standard deviation within 0.94 mm. CONCLUSIONS: SI and CI techniques are tested to provide a valid way to measure CyberKnife® beam shape in this study. Meanwhile, the systematic comparison of SI and CI also provides evidence for the measurement methods selection appropriately.

3.
Chem Commun (Camb) ; 2024 Sep 09.
Article in English | MEDLINE | ID: mdl-39248658

ABSTRACT

A photocatalytic trifluoromethylation/cyclization reaction of N-allyl and N-homoallyl aldehyde hydrazones with trifluoromethyl thianthrenium triflate was developed for the synthesis of trifluoromethylated dihydropyrazoles and tetrahydropyridazines. Besides, PhI(O2CCHF2)2 was employed to realize the construction of difluoromethylated dihydropyrazoles and tetrahydropyridazines. These protocols exhibit a broad substrate scope and good functional group tolerance.

4.
Sci Data ; 11(1): 1002, 2024 Sep 14.
Article in English | MEDLINE | ID: mdl-39277624

ABSTRACT

Brontispa longissima is a highly destructive pest that affects coconut and ornamental palm plants. It is widely distributed across Southeast and East Asia and the Pacific region, causing production losses of up to 50-70%. While control methods and ecological phenomena have been the primary focus of research, there is a significant lack of studies on the molecular mechanisms underlying these ecological phenomena. The absence of a reference genome has also hindered the development of new molecular-targeted control technologies. In this study, we conducted a karyotype analysis of B. longissima and assembled the first high-quality chromosome-level genome. The assembled genome is 582.24 Mb in size, with a scaffold N50 size of 63.81 Mb, consisting of 10 chromosomes and a GC content of 33.71%. The BUSCO assessment indicated a completeness estimate of 98.1%. A total of 23,051 protein-coding genes were predicted. Our study provides a valuable genomic resource for understanding the mechanisms of adaptive evolution and facilitates the development of new molecular-targeted control methods for B. longissima.


Subject(s)
Base Composition , Animals , Karyotype
5.
BMC Med Educ ; 24(1): 1010, 2024 Sep 16.
Article in English | MEDLINE | ID: mdl-39285371

ABSTRACT

BACKGROUND: Interprofessional teamwork improves patient care quality, safety, and health outcomes. Interprofessional education (IPE) is crucial in today's medical education to prepare students for the workforce as integral members of a collaborative team. The diversity of IPE learners indicates the importance of exploring the relationship between learning styles and attitudes toward IPE. The purpose of this study was to investigate the relationship between learning styles and attitudes toward IPE. METHODS: A cross-sectional study was conducted between August 2023 and September 2023 in 49 colleges located in the south-eastern region of China. A convenience sampling approach was employed, selecting 500 students majoring in Clinical Medicine and Nursing. The students completed an online questionnaire, which included sociodemographic characteristics, educational characteristics, interprofessional educational characteristics, learning styles, and the readiness for interprofessional learning scale, and Kolb's learning style inventory. Descriptive statistics, Spearman's correlation, and multiple linear regression analysis were used to analyze the data. RESULTS: The most learners are diverger (93.2%), followed by assimilator (3.4%), accommodator (2.6%), and Converger (0.8%). The total score on the RIPLS was 69.70 (7.42), ranging from 48 to 88. A statistical relationship could be established between learning styles and attitudes toward IPE. CONCLUSION: Abstract conceptualization and active experimentation learning modes and convergers were closely linked with positive attitudes toward IPE. Gender, age, and study stress can affect attitudes toward IPE. This study highlights the need for medical education curricula to integrate innovative teaching methods such as PBL, role-playing, scenario simulation and clinical early exposure to strengthen professional identity, and improve abilities related to interprofessional learning.


Subject(s)
Attitude of Health Personnel , Interprofessional Education , Learning , Students, Medical , Humans , Cross-Sectional Studies , Students, Medical/psychology , Male , Female , China , Adult , Interprofessional Relations , Young Adult , Surveys and Questionnaires
6.
Am J Transl Res ; 16(8): 4071-4082, 2024.
Article in English | MEDLINE | ID: mdl-39262759

ABSTRACT

Medical device research and development are characterized by high costs, extended timelines, inherent risks, and the necessity for interdisciplinary knowledge and skills. It is significantly influenced by policies, making the understanding of medical device innovation both important and challenging. This paper takes a dual approach to analyze medical device innovation. We reviewed representative clinical product of bougie and stylet and summarized the common characteristics and trend of these product. Innovations in these products often involve adding depth markings, replacing material and design structure, enhancing visualization, deciding between reusable or disposable designs, and integrating multi-functional features. This underscores the delicate balance between technological advancements and medical costs for widespread clinical applicability. We explored the guiding role of policy in medical device innovation, emphasizing its impact through an analysis of medical device regulations and policies in China. By offering insights from the perspectives of medical device companies and regulators, this paper aims to elucidate the critical aspects of medical device innovation, assisting researchers in mitigating risks during product development.

7.
Phytomedicine ; 134: 155968, 2024 Aug 23.
Article in English | MEDLINE | ID: mdl-39217651

ABSTRACT

BACKGROUND: The incidence of hypertriglyceridemia-associated acute pancreatitis (HTG-AP) is increasing globally and more so in China. The characteristics of liver-mediated metabolites and related key enzymes are rarely reported in HTG-AP. Chaiqin chengqi decoction (CQCQD) has been shown to protect against AP including HTG-AP in both patients and rodent models, but the underlying mechanisms in HTG-AP remain unexplored. PURPOSE: To assess the characteristics of liver-mediated metabolism and the therapeutic mechanisms of CQCQD in HTG-AP. METHODS: Male human apolipoprotein C3 transgenic (hApoC3-Tg; leading to HTG) mice or wild-type littermates received 7 intraperitoneal injections of cerulein (100 µg/kg) to establish HTG-AP and CER-AP, respectively. In HTG-AP, some mice received CQCQD (5.5 g/kg) gavage at 1, 5 or 9 h after disease induction. AP severity and related liver injury were determined by serological and histological parameters; and underlying mechanisms were identified by lipidomics and molecular biology. Molecular docking was used to identify key interactions between CQCQD compounds and metabolic enzymes, and subsequently validated in vitro in hepatocytes. RESULTS: HTG-AP was associated with increased disease severity indices including augmented liver injury compared to CER-AP. CQCQD treatment reduced severity and liver injury of HTG-AP. Glycerophospholipid (GPL) metabolism was the most disturbed pathway in HTG-AP in comparison to HTG alone. In HTG-AP, the mRNA level of GPL enzymes involved in phosphocholine (PC) and phosphatidylethanolamine (PE) synthesis (Pcyt1a, Pcyt2, Pemt, and Lpcat) were markedly upregulated in the liver. Of the GPL metabolites, lysophosphatidylethanolamine LPE(16:0) in serum of HTG-AP was significantly elevated and positively correlated with the pancreas histopathology score (r = 0.65). In vitro, supernatant from Pcyt2-overexpressing hepatocytes co-incubated with LPE(16:0) or phospholipase A2 (a PC- and PE-hydrolyzing enzyme) alone induced pancreatic acinar cell death. CQCQD treatment downregulated PCYT1a and PCYT2 enzyme levels in the liver. Hesperidin and narirutin were identified top two CQCQD compounds with highest affinity docking to PCYT1a and PCYT2. Both hesperidin and narirutin reduced the level of some GPL metabolites in hepatocytes. CONCLUSION: Liver-mediated GPL metabolism is excessively activated in HTG-AP with serum LPE(16:0) level correlating with disease severity. CQCQD reduces HTG-AP severity partially via modulating key enzymes in GPL metabolism pathway.

8.
Opt Lett ; 49(15): 4162-4165, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-39090884

ABSTRACT

Based on the x-ray absorption edges of different elements, we simultaneously image and distinguish the composition of three differently shaped components of an object by using energy-resolved x-ray absorption ghost imaging (GI). The initial x-ray beam is spatially modulated by a series of Hadamard matrix masks, and the object is composed of three pieces of Mo, Ag, and Sn foil in the shape of a triangle, square, and circle, respectively. The transmitted x-ray intensity is measured by an energy-resolved single-pixel detector with a spectral resolution better than 0.8 keV. Through correlation of the transmission spectra with the corresponding Hadamard patterns, the spectral image of the sample is reconstructed, with a spatial resolution of 108 µm. Our experiment demonstrates a practical application of spectral ghost imaging, which has important potential for the noninvasive analysis of material composition and distribution in biology, medical science, and many other fields.

9.
World J Clin Cases ; 12(23): 5299-5303, 2024 Aug 16.
Article in English | MEDLINE | ID: mdl-39156081

ABSTRACT

Clear cell sarcoma (CCS) is a rare melanocytic soft tissue sarcoma known for its propensity to metastasize to the lymph nodes and typically has an unfavorable prognosis. Currently, surgical resection is the primary treatment for localized CCS, while radiotherapy and chemotherapy are preferred for metastatic cases. The roles of adjuvant chemotherapy, radiotherapy, and lymph node dissection are controversial. Although immunotherapy has emerged as a promising avenue in CCS treatment research, there are no established clinical standards for postoperative follow-up. This editorial discusses a recent article by Liu et al, with a focus on current diagnostic modalities, treatment approaches, and the challenging prognosis associated with CCS. Our aim is to underscore the importance of long-term patient follow-up in CCS management.

10.
J Clin Med ; 13(16)2024 Aug 16.
Article in English | MEDLINE | ID: mdl-39200971

ABSTRACT

Objectives: This study aims to analyze the clinical characteristics of elderly patients with acute pancreatitis (AP) and investigate the effects of age on the clinical outcomes of AP. Methods: Patients aged ≥ 18 years with AP admitted within 72 h from 1 September 2013 to 31 August 2019 were included. Patients were divided into elderly (≥60 years) and non-elderly (<60 years) groups. Clinical data and outcomes were compared. Results: A total of 756 elderly and 4896 non-elderly patients with AP were included. The elderly patients had different etiological distributions and more severe clinical markers and scores. Age was an independent risk factor for mortality [odds ratio (OR): 2.911, 95% CI: 1.801-4.706, p < 0.001], intensive care unit admission (OR: 1.739, 95% CI: 1.126-2.685, p = 0.013), persistent organ failure (OR: 1.623, 95% CI: 1.326-1.987, p < 0.001), multiple organ failure (OR: 1.757, 95% CI: 1.186-2.604, p = 0.005), and infection (OR: 2.451, 95% CI: 1.994-3.013, p < 0.001). Adjusted multiple logistic regression and trend analysis confirmed the risk of the age for the outcomes. The deaths of elderly patients showed a biphasic pattern with peaks in the first and fifth weeks, in contrast to the single peak in the first week in the non-elderly patients. Conclusions: Elderly patients with AP were associated with worse clinical outcomes. It is crucial to devote considerable attention to the optimization of therapeutic approaches to reduce late mortality in this group of patients.

11.
Int Immunopharmacol ; 140: 112740, 2024 Oct 25.
Article in English | MEDLINE | ID: mdl-39116500

ABSTRACT

While Resolvin D1 (RvD1) shows promise in resolving inflammation in experimental autoimmune encephalomyelitis (EAE), its pro-resolving roles on dendritic cells (DCs) remain unknown, and the chemical instability of RvD1 poses significant challenges to its drug development. This study aims to investigate whether 4-(2'-methoxyphenyl)-1-[2'-[N-(2″-pyridinyl)-p-fluorobenzamido]ethyl]piperazine (p-MPPF), a novel chemically stable analogue of RvD1, can play a pro-resolving role in EAE, particularly on DCs, and if p-MPPF could serve as a potential substitute for RvD1. We showed that both RvD1 and p-MPPF mediated the resolution of inflammation in EAE, as evidenced by ameliorated EAE progression, attenuated pathological changes in the spinal cord, altered cytokine expression profile in serum, and reduced proportion of pro-inflammatory immune cells in the spleen. Utilizing DCs derived from both the spleen and bone marrow of EAE, our investigation showed that RvD1 and p-MPPF prevented DC maturation, decreased pro-inflammatory cytokine secretion, shifted DCs away from a pro-inflammatory phenotype, increased the phagocytosis capacity of DCs, and suppressed their ability to induce differentiation of CD4+ T cells into Th1 and Th17 subsets. For underlying intracellular mechanisms, we found that RvD1 and p-MPPF down-regulated the lactate dehydrogenase A signaling pathways. Comparisons between RvD1 and p-MPPF showed that they exerted overlapped pro-resolving effects to a large extent. This study demonstrates that both RvD1 and p-MPPF exert therapeutic effects on EAE by mediating inflammation resolution, which is closely associated with modulating DC immune function towards a tolerogenic phenotype. SPM mimetics may serve as a more promising therapeutic drug.


Subject(s)
Cytokines , Dendritic Cells , Docosahexaenoic Acids , Encephalomyelitis, Autoimmune, Experimental , Mice, Inbred C57BL , Encephalomyelitis, Autoimmune, Experimental/drug therapy , Encephalomyelitis, Autoimmune, Experimental/immunology , Animals , Dendritic Cells/drug effects , Dendritic Cells/immunology , Docosahexaenoic Acids/therapeutic use , Docosahexaenoic Acids/pharmacology , Docosahexaenoic Acids/chemistry , Female , Mice , Cytokines/metabolism , Anti-Inflammatory Agents/therapeutic use , Anti-Inflammatory Agents/pharmacology , Spinal Cord/drug effects , Spinal Cord/immunology , Spinal Cord/pathology , Spinal Cord/metabolism , Inflammation/drug therapy , Inflammation/immunology , Piperazines/pharmacology , Piperazines/therapeutic use , Piperazines/chemistry , Cells, Cultured , Spleen/drug effects , Spleen/immunology , Th17 Cells/immunology , Th17 Cells/drug effects
12.
Plant Phenomics ; 6: 0193, 2024.
Article in English | MEDLINE | ID: mdl-39144674

ABSTRACT

Cucumber is an important vegetable crop that has high nutritional and economic value and is thus favored by consumers worldwide. Exploring an accurate and fast technique for measuring the morphological traits of cucumber fruit could be helpful for improving its breeding efficiency and further refining the development models for pepo fruits. At present, several sets of measurement schemes and standards have been proposed and applied for the characterization of cucumber fruits; however, these manual methods are time-consuming and inefficient. Therefore, in this paper, we propose a cucumber fruit morphological trait identification framework and software called CucumberAI, which combines image processing techniques with deep learning models to efficiently identify up to 51 cucumber features, including 32 newly defined parameters. The proposed tool introduces an algorithm for performing cucumber contour extraction and fruit segmentation based on image processing techniques. The identification framework comprises 6 deep learning models that combine fruit feature recognition rules with MobileNetV2 to construct a decision tree for fruit shape recognition. Additionally, the framework employs U-Net segmentation models for fruit stripe and endocarp segmentation, a MobileNetV2 model for carpel classification, a ResNet50 model for stripe classification and a YOLOv5 model for tumor identification. The relationships between the image-based manual and algorithmic traits are highly correlated, and validation tests were conducted to perform correlation analyses of fruit surface smoothness and roughness, and a fruit appearance cluster analysis was also performed. In brief, CucumberAI offers an efficient approach for extracting and analyzing cucumber phenotypes and provides valuable information for future cucumber genetic improvements.

13.
Heliyon ; 10(15): e34337, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-39144986

ABSTRACT

The global epidemic caused by SARS-CoV-2 has brought about worldwide burden and a sense of danger for more than two years, leading to a wide range of social, public health, economic and environmental issues. Self-inoculation through hands has been the primary way for environmental transmission of SARS-CoV-2. Plasma-activated water (PAW) has been reported as an effective, safe and environmentally friendly disinfectant against SARS-CoV-2. However, the inactivating effect of PAW on SARS-CoV-2 located on skin surface and its underlying mechanism of action have not been elucidated. In this study, PAW was prepared using an air-pressure plasma jet device. The antiviral efficiency of PAW1, PAW3, and PAW5 on the SARS-CoV-2 pseudovirus was 8.20 % (±2.88 %), 46.24 % (±1.79 %), and 91.71 % (±0.47 %), respectively. Additionally, determination of PAW's physicochemical properties, identification of major sterile effector in PAW, transmission electron microscopy analysis, malondialdehyde (MDA) assessment, SDS-PAGE, ELISA, and qPCR were conducted to reveal the virucidal mechanism of PAW. Our experimental results suggested that peroxynitrite, which was generated by the synergism of acidic environment and reactive species, was the major sterile effector of PAW. Furthermore, we found that PAW treatment significantly inactivated SARS-CoV-2 pseudovirus through the destruction of its structure of and the degradation of the viral RNA. Therefore, the possible mechanism for the structural destruction of SARS-COV-2 by PAW is through the action of peroxynitrite generated by the synergism of acidic environment and reactive species, which might react with and destroy the lipid envelope of SARS-CoV-2 pseudovirus. Nevertheless, further studies are required to shed light on the interaction mechanism of PAW-inherent RONS and viral components, and to confirm the determinant factors for virus inactivation of SARS-COV-2 by PAW. Therefore, PAW may be a candidate hand disinfectant used to disrupt the transmission of SARS-CoV-2.

14.
Foods ; 13(15)2024 Jul 23.
Article in English | MEDLINE | ID: mdl-39123508

ABSTRACT

The aim of this study was to assess the advantages of an industry-scale microfluidizer system (ISMS) to prepare whole-grain highland barley pulp (WHBP) compared with colloid milling. Storage stability was evaluated by particle size, gravity separation stability, and rheological properties, as well as the microstructure observation by scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLMS). The results showed that colloid milling failed to effectively homogenize the material, while ISMS sample surfaces were compact and smooth at higher pressures according to visual observation and SEM. The Turbiscan stability index of WHBP by ISMS was much lower as a result of colloid milling, demonstrating ISMS can improve WHBP stability. WHBP by colloid milling displayed a three-peak particle size distribution pattern, while a single-peak pattern was evident after ISMS treatment. A higher shear rate decreased the apparent viscosity, suggesting that WHBP was a shear-thinning fluid. According to CLMS, ISMS can successfully improve homogenization by disrupting the structures of oil bodies, proteins, and starches. The WHBP prepared by ISMS exhibited a higher ß-glucan level than that prepared by colloid milling, and showed a significant increase in ß-glucan level with ISMS pressure. These findings indicate that using ISMS to produce WHBP is viable for enhancing its storage stability and nutritional value.

15.
ACS Nano ; 18(32): 21236-21245, 2024 Aug 13.
Article in English | MEDLINE | ID: mdl-39086003

ABSTRACT

The detection of mid-infrared light, covering a variety of molecular vibrational spectra, is critical for both civil and military purposes. Recent studies have highlighted the potential of two-dimensional topological semimetals for mid-infrared detection due to their advantages, including van der Waals (vdW) stacking and gapless electronic structures. Among them, mid-infrared photodetectors based on type-II Dirac semimetals have been less studied. In this paper, we present a silicon waveguide integrated type-II Dirac semimetal platinum telluride (PtTe2) mid-infrared photodetector, and further improve detection performance by using PtTe2-graphene heterostructure. For the fabricated silicon waveguide-integrated PtTe2 photodetector, with an external bias voltage of -10 mV and an input optical power of 86 nW, the measured responsivity is 2.7 A/W at 2004 nm and a 3 dB bandwidth of 0.6 MHz is realized. For the fabricated silicon waveguide-integrated PtTe2-graphene photodetector, as the external bias voltage and input optical power are 0.5 V and 0.13 µW, a responsivity of 5.5 A/W at 2004 nm and a 3 dB bandwidth of 35 MHz are obtained. An external quantum efficiency of 119% can be achieved at an input optical power of 0.376 µW.

16.
Sci Rep ; 14(1): 18547, 2024 08 09.
Article in English | MEDLINE | ID: mdl-39122810

ABSTRACT

Observational studies have shown that non-alcoholic fatty liver disease (NAFLD) is strongly associated with metabolic dysfunction. However, there is a paucity of research on whether changes in indicators of serum metabolism contribute to the development of NAFLD. This study was conducted with 4084 participants who underwent healthy physical examinations at Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China, in 2022 and 2023. Baseline and follow-up measurements, including anthropometric data, abdominal ultrasound and blood samples were collected. The diagnosis of NAFLD was based on the 2010 Chinese Guidelines on Diagnosis and Treatment of NAFLD. Multiple logistic regression was utilized to analyze the odds ratios (ORs) for the 1-year risk of NAFLD in connection with both baseline metabolic indicators and changes in metabolic indicators observed over the course of 1 year. A total of 3425 study participants who were free of NAFLD at baseline, including 1146 men and 2279 women, were included in the final analysis. The mean age was 34.43 ± 7.20 years. Participants who developed NAFLD were older, male and had higher levels of body mass index (BMI), blood pressure, fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), free triiodothyronine (fT3), uric acid (UA), alanine aminotransferase (ALT) and aspartate aminotransferase (AST); and lower levels of high-density lipoprotein cholesterol (HDL-C) and free thyroxine (fT4) (all P values < 0.05). The multivariable model showed that baseline BMI, diastolic blood pressure (DBP), TG, TC, HDL-C, LDL-C, UA, fT4, fT3, ALT and changes in TG, HDL-C, and UA were associated with the 1-year risk of developing NAFLD. The risk of NAFLD increased by 56% [OR 1.56, 95% Confidence Interval (CI) 1.32-1.87] and 40% (OR 1.40, 95% CI 1.19-1.64) for each standard deviation (SD) increase in altered TG values (1.01 mmol/L) and altered UA values (55 µmol/L) respectively. Conversely, for each SD (0.27 mmol/L) increase in HDL-C change, the 1-year risk of incident NAFLD was reduced by 50% (OR 0.50, 95% CI 0.40-0.62). The present study suggested that increases in TG and UA, and decreases in HDL-C, significantly increase the risk of developing NAFLD. Therefore, more attention should be paid to these factors in the management and prevention of NAFLD.


Subject(s)
Lipids , Non-alcoholic Fatty Liver Disease , Uric Acid , Humans , Non-alcoholic Fatty Liver Disease/blood , Non-alcoholic Fatty Liver Disease/epidemiology , Male , Female , Uric Acid/blood , Adult , China/epidemiology , Lipids/blood , Middle Aged , Risk Factors , Incidence , Body Mass Index
17.
Mediators Inflamm ; 2024: 7275309, 2024.
Article in English | MEDLINE | ID: mdl-39118979

ABSTRACT

Inflammatory bowel disease (IBD), which encompasses Crohn's disease (CD) and ulcerative colitis (UC), is a complicated illness whose exact cause is yet unknown. Necroptosis is associated with IBD pathogenesis, leading to intestinal barrier abnormalities and uncontrolled inflammation. Molecules involved in necroptosis, however, exhibit different expression levels in IBD and its associated colorectal cancer. Multiple studies have shown that inhibiting these molecules alleviates necroptosis-induced IBD. Moreover, due to the severe scarcity of clinical medications for treating IBD caused by necroptosis, we review the various functions of crucial necroptosis molecules in IBD, the stimuli regulating necroptosis, and the current emerging therapeutic strategies for treating IBD-associated necroptosis. Eventually, understanding the pathogenesis of necroptosis in IBD will enable the development of additional therapeutic approaches for the illness.


Subject(s)
Inflammatory Bowel Diseases , Necroptosis , Humans , Inflammatory Bowel Diseases/metabolism , Inflammatory Bowel Diseases/pathology , Animals , Colitis, Ulcerative/metabolism , Colitis, Ulcerative/pathology , Crohn Disease/metabolism , Crohn Disease/pathology
18.
Int J Mol Sci ; 25(15)2024 Jul 23.
Article in English | MEDLINE | ID: mdl-39125595

ABSTRACT

Polycyclic polyprenylated acylphloroglucinols (PPAPs) comprise a large group of compounds of mostly plant origin. The best-known compound is hyperforin from St. John's wort with its antidepressant, antitumor and antimicrobial properties. The chemical synthesis of PPAP variants allows the generation of compounds with improved activity and compatibility. Here, we studied the antimicrobial activity of two synthetic PPAP-derivatives, the water-insoluble PPAP23 and the water-soluble sodium salt PPAP53. In vitro, both compounds exhibited good activity against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium. Both compounds had no adverse effects on Galleria mellonella wax moth larvae. However, they were unable to protect the larvae from infection with S. aureus because components of the larval coelom neutralized the antimicrobial activity; a similar effect was also seen with serum albumin. In silico docking studies with PPAP53 revealed that it binds to the F1 pocket of human serum albumin with a binding energy of -7.5 kcal/mol. In an infection model of septic arthritis, PPAP23 decreased the formation of abscesses and S. aureus load in kidneys; in a mouse skin abscess model, topical treatment with PPAP53 reduced S. aureus counts. Both PPAPs were active against anaerobic Gram-positive gut bacteria such as neurotransmitter-producing Clostridium, Enterococcus or Ruminococcus species. Based on these results, we foresee possible applications in the decolonization of pathogens.


Subject(s)
Ketones , Methicillin-Resistant Staphylococcus aureus , Spiro Compounds , Animals , Humans , Mice , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Enterococcus faecium/drug effects , Ketones/chemistry , Ketones/pharmacology , Larva/drug effects , Methicillin-Resistant Staphylococcus aureus/drug effects , Microbial Sensitivity Tests , Molecular Docking Simulation , Moths/drug effects , Spiro Compounds/chemistry , Spiro Compounds/pharmacology , Staphylococcal Infections/drug therapy
19.
Eur J Med Chem ; 277: 116712, 2024 Nov 05.
Article in English | MEDLINE | ID: mdl-39106657

ABSTRACT

Quaternization of ruthenium complexes may be a promising strategy for the development of new antibiotics. In response to the increasing bacterial resistance, we integrated the quaternary amine structure into the design of ruthenium complexes and evaluated their antibacterial activity. All the ruthenium complexes showed good antibacterial activity against the tested Staphylococcus aureus (S. aureus). Ru-8 was the most effective antibacterial agent that displayed excellent antibacterial activity against S. aureus (MIC = 0.78-1.56 µg/mL). In vitro experiments showed that all nine ruthenium complexes had low hemolytic toxicity to rabbit erythrocytes. Notably, Ru-8 was found to disrupt bacterial cell membranes, alter their permeability, and induce ROS production in bacteria, all the above leading to the death of bacteria without inducing drug resistance. To further explore the antibacterial activity of Ru-8in vivo, we established a mouse skin wound infection model and a G. mellonella larvae infection model. Ru-8 exhibited significant antibacterial efficacy against S. aureus in vivo and low toxicity to mouse tissues. The Ru-8 showed low toxicity to Raw264.7 cells (mouse monocyte macrophage leukemia cells). This study indicates that the ruthenium complex ruthenium quaternary was a promising strategy for the development of new antibacterial agents.


Subject(s)
Anti-Bacterial Agents , Coordination Complexes , Microbial Sensitivity Tests , Pyridines , Ruthenium , Staphylococcus aureus , Thiazoles , Staphylococcus aureus/drug effects , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/chemical synthesis , Animals , Mice , Ruthenium/chemistry , Ruthenium/pharmacology , Pyridines/chemistry , Pyridines/pharmacology , Pyridines/chemical synthesis , Coordination Complexes/pharmacology , Coordination Complexes/chemistry , Coordination Complexes/chemical synthesis , Rabbits , Structure-Activity Relationship , Thiazoles/chemistry , Thiazoles/pharmacology , Thiazoles/chemical synthesis , Molecular Structure , RAW 264.7 Cells , Drug Discovery , Dose-Response Relationship, Drug , Staphylococcal Infections/drug therapy , Hemolysis/drug effects
20.
Acta Crystallogr C Struct Chem ; 80(Pt 9): 538-544, 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-39120498

ABSTRACT

Luminescent CuI complexes are an important class of coordination compounds due to their relative abundance, low cost and ability to display excellent luminescence. The title Cu2I2P2S2-type binuclear complex, di-µ-iodido-bis[(thiourea-κS)(triphenylphosphine-κP)copper(I)], [Cu2I2(CH4N2S)2(C18H15P)2], conventionally abbreviated as Cu2I2TPP2TU2, where TPP and TU represent triphenylphosphine and thiourea, respectively, is described. In this complex, each CuI atom adopts a CuI2PS four-coordination mode and pairs of atoms are connected to each other by two µ2-I ligands to form a centrosymmetric binuclear cluster. It was also found that the paper-based film of this complex exhibited obvious luminescence light-up sensing for pyridine and 4-methylpyridine.

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