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1.
BMC Gastroenterol ; 24(1): 173, 2024 May 18.
Article in English | MEDLINE | ID: mdl-38762503

ABSTRACT

BACKGROUND: There have been previous studies and earlier systematic review on the relationship between inflammatory bowel disease (IBD) and radiation exposure. With the diversification of current test methods, this study intended to conduct a meta-analysis to evaluate the IBD radiation exposure in recent years. METHODS: Three databases (PUBMED, EMBASE, and MEDICINE) for relevant literature up to May 1, 2023 were searched. The statistical data meeting requirements were collated and extracted. RESULTS: 20 papers were enrolled. The overall high radiation exposure rate was 15% (95% CI = [12%, 19%]) for CD and 5% (95% CI = [3%, 7%]) for UC. The pooled result found that high radiation exposure rate was 3.44 times higher in CD than in UC (OR = 3.44, 95% CI = [2.35, 5.02]). Moreover, the average radiation exposure level in CD was 12.77 mSv higher than that in UC (WMD = 12.77, 95% CI = [9.93, 15.62] mSv). Furthermore, radiation exposure level of CD after 2012 was higher than those before 2012 (26.42 ± 39.61vs. 23.76 ± 38.46 mSv, P = 0.016), while UC did not show similar result (11.99 ± 27.66 vs. 10.01 ± 30.76 mSv, P = 0.1). Through subgroup analysis, it was found that disease duration (WMD = 2.75, 95% CI = [0.10, 5.40] mSv), complications (OR = 5.09, 95% CI = [1.50, 17.29]), and surgical history (OR = 5.46, 95% CI = [1.51, 19.69]) significantly increased the proportion of high radiation exposure. CONCLUSION: This study found that radiation exposure level of IBD patients was high, which revealed the radiation risk in the process of diagnosis and treatment of IBD patients. In the future, longer follow-up and prospective studies are needed to reveal the relationship between high radiation exposure and solid tumorigenesis.


Subject(s)
Radiation Exposure , Humans , Radiation Exposure/adverse effects , Colitis, Ulcerative , Inflammatory Bowel Diseases , Crohn Disease , Radiation Dosage
2.
Int J Biol Macromol ; : 132408, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38754683

ABSTRACT

Porcine Epidemic Diarrhea Virus (PEDV) is a highly contagious virus that causes Porcine Epidemic Diarrhea (PED). This enteric disease results in high mortality rates in piglets, leading to significant financial losses in the pig industry. However, vaccines cannot provide sufficient protection against epidemic strains. Spike (S) protein exposed on the surface of virion mediates PEDV entry into cells. Our findings imply that matrine (MT), a naturally occurring alkaloid, inhibits PEDV infection targeting S protein of virions and biological process of cells. The GLY434 residue in the autodocking site of the S protein and MT conserved based on sequence comparison. This study provides a comprehensive analysis of viral attachment, entry, and virucidal effects to investigate how that MT inhibits virus replication. MT inhibits PEDV attachment and entry by targeting S protein. MT was added to cells before, during, or after infection, it exhibits anti-PEDV activities and viricidal effects. Network pharmacology focuses on addressing causal mechanisms rather than just treating symptoms. We identified the key genes and screened the cell apoptosis involved in the inhibition of MT on PEDV infection in network pharmacology. MT significantly promotes cell apoptosis in PEDV-infected cells to inhibit PEDV infection by activating the MAPK signaling pathway. Collectively, we provide the biological foundations for the development of single components of traditional Chinese medicine to inhibit PEDV infection and spread.

3.
Heliyon ; 10(10): e30167, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38765025

ABSTRACT

Nowadays, lead poisoning in children commonly occurs, but lead poisoning caused by the administration of Tibetan medicine is rarely reported. This report describes the diagnosis and management of lead poisoning in a 16-year-old girl presented with abdominal pain, vomiting, and anemia with limb numbness, who had a childhood history of epilepsy and took Tibetan medicine intermittently to control the symptoms. After admission into hospital, Computed tomography showed high-density shadows in the gastrointestinal tract. Video-Electroencephalography showed no signs of seizure. Reflux esophagitis was observed in gastroscopy. And no obvious abnormalities in the colonic mucosa through colonoscopy. Bone marrow smear test showed basophilic stippling in the erythrocytes. The blood and urine lead levels of 626 and 75.9 µg/L, respectively. We therefore considered lead poisoning, and the patient improved after chelation therapy. Due to its atypical clinical manifestations, lead poisoning is easily misdiagnosed. Thus, clinicians should pay more attention to this disease. When abdominal pain, anemia, and neurological symptoms are present, the possibility of lead poisoning should be considered.

4.
Nat Cell Biol ; 2024 May 07.
Article in English | MEDLINE | ID: mdl-38714852

ABSTRACT

Upon endoplasmic reticulum (ER) stress, activation of the ER-resident transmembrane protein kinase/endoribonuclease inositol-requiring enzyme 1 (IRE1) initiates a key branch of the unfolded protein response (UPR) through unconventional splicing generation of the transcription factor X-box-binding protein 1 (XBP1s). Activated IRE1 can form large clusters/foci, whose exact dynamic architectures and functional properties remain largely elusive. Here we report that, in mammalian cells, formation of IRE1α clusters is an ER membrane-bound phase separation event that is coupled to the assembly of stress granules (SGs). In response to different stressors, IRE1α clusters are dynamically tethered to SGs at the ER. The cytosolic linker portion of IRE1α possesses intrinsically disordered regions and is essential for its condensation with SGs. Furthermore, disruption of SG assembly abolishes IRE1α clustering and compromises XBP1 mRNA splicing, and such IRE1α-SG coalescence engenders enrichment of the biochemical components of the pro-survival IRE1α-XBP1 pathway during ER stress. Our findings unravel a phase transition mechanism for the spatiotemporal assembly of IRE1α-SG condensates to establish a more efficient IRE1α machinery, thus enabling higher stress-handling capacity.

6.
Discov Oncol ; 15(1): 179, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38772985

ABSTRACT

AIMS: The aim of this study is to enhance the accuracy of monitoring and treatment information for patients diagnosed with colorectal cancer (CRC). METHODS: Utilizing the Surveillance, Epidemiology, and End Results (SEER) database, a cohort of 335,948 eligible CRC patients was included in this investigation. Conditional survival probability and actuarial overall survival were employed as methodologies to investigate the association between clinicopathological characteristics and cancer prognosis. RESULTS: Among CRC patients, the 5-year survival rate was 59%, while the 10-year survival rate was 42%. Over time, conditional survival showed a consistent increase, with rates reaching 45% and 48% for individuals surviving 1 and 2 years, respectively. Notably, patients with unfavorable tumor stages exhibited substantial improvements in conditional survival, thereby narrowing the disparity with actuarial overall survival over time. CONCLUSION: This study underscores the significance of time-dependent conditional survival probability, particularly for patients with a poorer prognosis. The findings suggest that long-term CRC survivors may experience improved cancer prognosis over time.

7.
ACS Cent Sci ; 10(3): 628-636, 2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38559293

ABSTRACT

Angelica sinensis, commonly known as Dong Quai in Europe and America and as Dang-gui in China, is a medicinal plant widely utilized for the prevention and treatment of osteoporosis. In this study, we report the discovery of a new category of phthalide from Angelica sinensis, namely falcarinphthalides A and B (1 and 2), which contains two fragments, (3R,8S)-falcarindiol (3) and (Z)-ligustilide (4). Falcarinphthalides A and B (1 and 2) represent two unprecedented carbon skeletons of phthalide in natural products, and their antiosteoporotic activities were evaluated. The structures of 1 and 2, including their absolute configurations, were established using extensive analysis of NMR spectra, chemical derivatization, and ECD/VCD calculations. Based on LC-HR-ESI-MS analysis and DFT calculations, a production mechanism for 1 and 2 involving enzyme-catalyzed Diels-Alder/retro-Diels-Alder reactions was proposed. Falcarinphthalide A (1), the most promising lead compound, exhibits potent in vitro antiosteoporotic activity by inhibiting NF-κB and c-Fos signaling-mediated osteoclastogenesis. Moreover, the bioinspired gram-scale total synthesis of 1, guided by intensive DFT study, has paved the way for further biological investigation. The discovery and gram-scale total synthesis of falcarinphthalide A (1) provide a compelling lead compound and a novel molecular scaffold for treating osteoporosis and other metabolic bone diseases.

8.
Plant Mol Biol ; 114(3): 37, 2024 Apr 11.
Article in English | MEDLINE | ID: mdl-38602592

ABSTRACT

Reactive oxygen species (ROS) is a chemically reactive chemical substance containing oxygen and a natural by-product of normal oxygen metabolism. Excessive ROS affect the growth process of crops, which will lead to the decrease of yield. Nitrogen, as a critical nutrient element in plants and plays a vital role in plant growth and crop production. Nitrate is the primary nitrogen source available to plants in agricultural soil and various natural environments. However, the molecular mechanism of ROS-nitrate crosstalk is still unclear. In this study, we used the foxtail millet (Setaria italica L.) as the material to figure it out. Here, we show that excessive NaCl inhibits nitrate-promoted plant growth and nitrogen use efficiency (NUE). NaCl induces ROS accumulation in roots, and ROS inhibits nitrate-induced gene expression in a short time. Surprisingly, low concentration ROS slight promotes and high concentration of ROS inhibits foxtail millet growth under long-term H2O2 treatment. These results may open a new perspective for further exploration of ROS-nitrate signaling pathway in plants.


Subject(s)
Nitrates , Setaria Plant , Reactive Oxygen Species , Nitrates/pharmacology , Setaria Plant/genetics , Hydrogen Peroxide , Sodium Chloride , Oxygen , Signal Transduction , Gene Expression Profiling , Nitrogen
9.
Front Neurol ; 15: 1351335, 2024.
Article in English | MEDLINE | ID: mdl-38606278

ABSTRACT

Background: Neuroimaging studies have suggested a pivotal role for the amygdala involvement in chronic low back pain (CLBP). However, the relationship between the amygdala subregions and CLBP has not yet been delineated. This study aimed to analyze whether the amygdala subregions were linked to the development of CLBP. Methods: A total of 45 patients with CLBP and 45 healthy controls (HCs) were included in this study. All subjects were asked to complete a three-dimensional T1-weighted magnetic resonance imaging (3D-T1 MRI) scan. FreeSurfer 7.3.2 was applied to preprocess the structural MRI images and segment the amygdala into nine subregions. Afterwards, comparisons were made between the two groups in terms of the volumes of the amygdala subregions. Correlation analysis is utilized to examine the relationship between the amygdala subregion and the scale scores, as well as the pain duration in patients with CLBP. Additionally, logistic regression was used to explore the risk of the amygdala and its subregions for CLBP. Results: In comparison to HCs, patients with CLBP exhibited a significant enlargement of the left central nucleus (Ce) and left cortical nucleus (Co). Furthermore, the increased volume of the left Ce was associated with a higher risk of CLBP. Conclusion: Our study suggests that the left Ce and left Co may be involved in the pathophysiological processes of CLBP. Moreover, the volume of the left Ce may be a biomarker for detecting the risk of CLBP.

10.
Int J Ophthalmol ; 17(4): 646-652, 2024.
Article in English | MEDLINE | ID: mdl-38638261

ABSTRACT

AIM: To evaluate the effect of bone morphogenetic protein-6 (BMP-6) on transforming growth factor (TGF)-ß2-induced epithelial-mesenchymal transition (EMT) in retinal pigment epithelium (RPE). METHODS: Adult retinal pigment epithelial cell line (ARPE-19) were randomly divided into control, TGF-ß2 (5 µg/L), and BMP-6 small interfering RNA (siRNA) group. The cell morphology was observed by microscopy, and the cell migration ability were detected by Transwell chamber. The EMT-related indexes and BMP-6 protein levels were detected by Western blotting. Furthermore, a BMP-6 overexpression plasmid was constructed and RPE cells were divided into the control group, TGF-ß2+empty plasmid group, BMP-6 overexpression group, and TGF-ß2+BMP-6 overexpression group. The EMT-related indexes and extracellular regulated protein kinases (ERK) protein levels were detected. RESULTS: Compared with the control group, the migration of RPE cells in the TGF-ß2 group was significantly enhanced. TGF-ß2 increased the protein expression levels of α-smooth muscle actin (α-SMA), fibronectin and vimentin but significantly decreased the protein levels of E-cadherin and BMP-6 (P<0.05) in RPE. Similarly, the migration of RPE cells in the BMP-6 siRNA group was also significantly enhanced. BMP-6 siRNA increased the protein expression levels of α-SMA, fibronectin and vimentin but significantly decreased the protein expression levels of E-cadherin (P<0.05). Overexpression of BMP-6 inhibited the migration of RPE cells induced by TGF-ß2 and prevented TGF-ß2 from affecting EMT-related biomarkers (P<0.05). CONCLUSION: BMP-6 prevents the EMT in RPE cells induced by TGF-ß2, which may provide a theoretical basis for the prevention and treatment of proliferative vitreoretinopathy.

11.
Proc Natl Acad Sci U S A ; 121(15): e2309087121, 2024 Apr 09.
Article in English | MEDLINE | ID: mdl-38557184

ABSTRACT

Africa carries a disproportionately high share of the global malaria burden, accounting for 94% of malaria cases and deaths worldwide in 2019. It is also a politically unstable region and the most vulnerable continent to climate change in recent decades. Knowledge about the modifying impacts of violent conflict on climate-malaria relationships remains limited. Here, we quantify the associations between violent conflict, climate variability, and malaria risk in sub-Saharan Africa using health surveys from 128,326 individuals, historical climate data, and 17,429 recorded violent conflicts from 2006 to 2017. We observe that spatial spillovers of violent conflict (SSVCs) have spatially distant effects on malaria risk. Malaria risk induced by SSVCs within 50 to 100 km from the households gradually increases from 0.1% (not significant, P>0.05) to 6.5% (95% CI: 0 to 13.0%). SSVCs significantly promote malaria risk within the average 20.1 to 26.9 °C range. At the 12-mo mean temperature of 22.5 °C, conflict deaths have the largest impact on malaria risk, with an approximately 5.8% increase (95% CI: 1.0 to 11.0%). Additionally, a pronounced association between SSVCs and malaria risk exists in the regions with 9.2 wet days per month. The results reveal that SSVCs increase population exposure to harsh environments, amplifying the effect of warm temperature and persistent precipitation on malaria transmission. Violent conflict therefore poses a substantial barrier to mosquito control and malaria elimination efforts in sub-Saharan Africa. Our findings support effective targeting of treatment programs and vector control activities in conflict-affected regions with a high malaria risk.


Subject(s)
Exposure to Violence , Malaria , Humans , Malaria/epidemiology , Africa South of the Sahara/epidemiology , Temperature
12.
Pharmaceutics ; 16(4)2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38675208

ABSTRACT

Electroporation (EP) stands out as a promising non-viral plasmid delivery strategy, although achieving optimal transfection efficiency in vivo remains a challenge. A noteworthy advancement in the field of in vivo EP is the application of hyaluronidase, an enzyme with the capacity to degrade hyaluronic acid in the extracellular matrix, which thereby enhances DNA transfer efficiency by 2- to 3-fold. This paper focuses on elucidating the mechanism of hyaluronidase's impact on transfection efficiency. We demonstrate that hyaluronidase promotes a more uniform distribution of plasmid DNA (pDNA) within skeletal muscle. Additionally, our study investigates the effect of the timing of hyaluronidase pretreatment on EP efficiency by including time intervals of 0, 5, and 30 min between hyaluronidase treatment and the application of pulses. Serum levels of the pDNA-encoded transgene reveal a minimal influence of the hyaluronidase pretreatment time on the final serum protein levels following delivery in both mice and rabbit models. Leveraging bioimpedance measurements, we capture morphological changes in muscle induced by hyaluronidase treatment, which result in a varied pDNA distribution. Subsequently, these findings are employed to optimize EP electrical parameters following hyaluronidase treatment in animal models. This paper offers novel insights into the potential of hyaluronidase in enhancing the effectiveness of in vivo EP, as well as guides optimized electroporation strategies following hyaluronidase use.

13.
J Am Chem Soc ; 146(18): 12723-12733, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38654452

ABSTRACT

Enfumafungin-type antibiotics, represented by enfumafungin and fuscoatroside, belong to a distinct group of triterpenoids derived from fungi. These compounds exhibit significant antifungal properties with ibrexafungerp, a semisynthetic derivative of enfumafungin, recently gaining FDA's approval as the first oral antifungal drug for treating invasive vulvar candidiasis. Enfumafungin-type antibiotics possess a cleaved E-ring with an oxidized carboxyl group and a reduced methyl group at the break site, suggesting unprecedented C-C bond cleavage chemistry involved in their biosynthesis. Here, we show that a 4-gene (fsoA, fsoD, fsoE, fsoF) biosynthetic gene cluster is sufficient to yield fuscoatroside by heterologous expression in Aspergillus oryzae. Notably, FsoA is an unheard-of terpene cyclase-glycosyltransferase fusion enzyme, affording a triterpene glycoside product that relies on enzymatic fusion. FsoE is a P450 enzyme that catalyzes successive oxidation reactions at C19 to facilitate a C-C bond cleavage, producing an oxidized carboxyl group and a reduced methyl group that have never been observed in known P450 enzymes. Our study thus sets the important foundation for the manufacture of enfumafungin-type antibiotics using biosynthetic approaches.


Subject(s)
Antifungal Agents , Antifungal Agents/chemistry , Antifungal Agents/pharmacology , Antifungal Agents/metabolism , Aspergillus oryzae/enzymology , Aspergillus oryzae/metabolism , Multigene Family , Triterpenes/chemistry , Triterpenes/metabolism , Cytochrome P-450 Enzyme System/metabolism
14.
J Pharm Sci ; 2024 Apr 28.
Article in English | MEDLINE | ID: mdl-38685452

ABSTRACT

A thorough understanding of effects of polymers on crystallization of amorphous drugs is essential for rational design of robust amorphous solid dispersion (ASD), since crystallization of the amorphous drug negates their solubility advantage. In this work, we measured the first nucleation time (t0, time to form the first critical nucleus in fresh liquid/glass) in posaconazole (POS)/polyvinylpyrrolidone vinyl acetate (PVPVA) and POS/polyvinylpyrrolidone (PVP K25) ASDs and showed that the polymer overlap concentration (c*, concentration above which adjacent polymer chains begin to contact) is critical in controlling crystallization of ASDs. When polymer concentration c < c*, t0 of POS ASDs is approximately equal to that of the neat amorphous POS, but it increases significantly when c > c*. This observation supports the view that the effective inhibitory effect of crystallization in ASDs above c* is primarily correlated with delay in the first nucleation event. Our finding is useful in efficient polymer selection and performance prediction of high drug loaded ASD formulations.

15.
Plant Mol Biol ; 114(3): 40, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38622367

ABSTRACT

Parasitic lifestyle can often relax the constraint on the plastome, leading to gene pseudogenization and loss, and resulting in diverse genomic structures and rampant genome degradation. Although several plastomes of parasitic Cuscuta have  been reported, the evolution of parasitism in the family Convolvulaceae which is linked to structural variations and reduction of plastome has not been well investigated. In this study, we assembled and collected 40 plastid genomes belonging to 23 species representing four subgenera of Cuscuta and ten species of autotrophic Convolvulaceae. Our findings revealed nine types of structural variations and six types of inverted repeat (IR) boundary variations in the plastome of Convolvulaceae spp. These structural variations were associated with the shift of parasitic lifestyle, and IR boundary shift, as well as the abundance of long repeats. Overall, the degradation of Cuscuta plastome proceeded gradually, with one clade exhibiting an accelerated degradation rate. We observed five stages of gene loss in Cuscuta, including NAD(P)H complex → PEP complex → Photosynthesis-related → Ribosomal protein subunits → ATP synthase complex. Based on our results, we speculated that the shift of parasitic lifestyle in early divergent time promoted relaxed selection on plastomes, leading to the accumulation of microvariations, which ultimately resulted in the plastome reduction. This study provides new evidence towards a better understanding of plastomic evolution, variation, and reduction in the genus Cuscuta.


Subject(s)
Convolvulaceae , Cuscuta , Genome, Plastid , Convolvulaceae/genetics , Cuscuta/genetics , Genes, Plant , Photosynthesis/genetics , Phylogeny , Evolution, Molecular
16.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 46(2): 210-216, 2024 Apr.
Article in Chinese | MEDLINE | ID: mdl-38686717

ABSTRACT

Objective To construct a scientific and practical management model of the hospice and palliative care outpatient clinic and provide a reference for the operation and development of the outpatient clinic. Methods The basic framework of the whole process management model of hospice and palliative care outpatient clinic was determined preliminarily by literature analysis,qualitative interviews and experts group meetings.Two rounds of consultation were conducted among 18 experts in hospice and palliative care and medical-nursing combined outpatient service by the Delphi method. Results The questionnaire response rates of the two rounds of expert consultation were both 100% and the authority coefficients of the two rounds of expert consultation were 0.88 and 0.91,respectively.Finally,the whole process management model of hospice and palliative care outpatient clinic was constructed,which was composed of three first-level indicators including staff composition,work structure and effect evaluation,5 second-level indicators and 62 third-level indicators. Conclusion The constructed whole process management model is scientific,innovative and continuous,which can provide a reference for the operation and development of the hospice and palliative care outpatient clinic.


Subject(s)
Ambulatory Care Facilities , Hospice Care , Palliative Care , Hospice Care/organization & administration , Ambulatory Care Facilities/organization & administration , Surveys and Questionnaires , Humans
17.
Brain Res Bull ; 212: 110968, 2024 Apr 27.
Article in English | MEDLINE | ID: mdl-38679110

ABSTRACT

BACKGROUND: Despite regional brain structural changes having been reported in patients with chronic low back pain (CLBP), the topological properties of structural covariance networks (SCNs), which refer to the organization of the SCNs, remain unclear. This study applied graph theoretical analysis to explore the alterations of the topological properties of SCNs, aiming to comprehend the integration and separation of SCNs in patients with CLBP. METHODS: A total of 38 patients with CLBP and 38 healthy controls (HCs), balanced for age and sex, were scanned using three-dimensional T1-weighted magnetic resonance imaging. The cortical thickness was extracted from 68 brain regions, according to the Desikan-Killiany atlas, and used to reconstruct the SCNs. Subsequently, graph theoretical analysis was employed to evaluate the alterations of the topological properties in the SCNs of patients with CLBP. RESULTS: In comparison to HCs, patients with CLBP had less cortical thickness in the left superior frontal cortex. Additionally, the cortical thickness of the left superior frontal cortex was negatively correlated with the Visual Analogue Scale scores of patients with CLBP. Furthermore, patients with CLBP, relative to HCs, exhibited lower global efficiency and small-worldness, as well as a longer characteristic path length. This indicates a decline in the brain's capacity to transmit and process information, potentially impacting the processing of pain signals in patients with CLBP and contributing to the development of CLBP. In contrast, there were no significant differences in the clustering coefficient, local efficiency, nodal efficiency, nodal betweenness centrality, or nodal degree between the two groups. CONCLUSIONS: From the regional cortical thickness to the complex brain network level, our study demonstrated changes in the cortical thickness and topological properties of the SCNs in patients with CLBP, thus aiding in a better understanding of the pathophysiological mechanisms of CLBP.

18.
ChemSusChem ; : e202301911, 2024 Mar 13.
Article in English | MEDLINE | ID: mdl-38477175

ABSTRACT

The multifunctional derivatization of alcohols has been achieved by the bipyridinium-based conjugated small molecule photocatalysts with redox center and Lewis acid site. Besides exhibiting high activity in the selective generation of aldehydes/ketones, acids from alcohols through solvent modulation, this system renders the first selective synthesis of esters via an attractive cross-coupling pattern, whose reaction route is significantly different from the traditional condensation of alcohols and acids or esterification from hemiacetals. Following the oxidization of alcohol to aldehyde via bipyridinium-mediated electron and energy transfer, the Lewis acid site of bipyridinium then activates the aldehyde and methanol to obtain the acetal, which further reacts with methanol to generate ester. This method not only demonstrates a clear advantage of bipyridinium in diverse catalytic activities, but also paves the way for designing efficient multifunctional small molecule photocatalysts. This metal- and additive-free photocatalytic esterification reaction marks a significant advancement towards a more environmentally friendly, cost-effective and green sustainable approach, attributed to the utilization of renewable substrate alcohol and the abundant, low-cost air as the oxidant. The mildness of this esterification reaction condition provides a more suitable alternative for large-scale industrial production of esters.

19.
Int Immunopharmacol ; 131: 111911, 2024 Apr 20.
Article in English | MEDLINE | ID: mdl-38527401

ABSTRACT

BACKGROUND: Acute lung injury (ALI) has garnered significant attention in the field of respiratory and critical care due to its high mortality and morbidity, and limited treatment options. The role of the endothelial barrier in the development of ALI is crucial. Several bacterial pathogenic factors, including the bacteria-derived formyl peptide (fMLP), have been implicated in damaging the endothelial barrier and initiating ALI. However, the mechanism by which fMLP causes ALI remains unclear. In this study, we aim to explore the mechanisms of ALI caused by fMLP and evaluate the protective effects of MOTS-c, a mitochondrial-derived peptide. METHODS: We established a rat model of ALI and a human pulmonary microvascular endothelial cell (HPMVEC) model of ALI by treatment with fMLP. In vivo experiments involved lung histopathology assays, assessments of inflammatory and oxidative stress factors, and measurements of ferroptosis-related proteins and barrier proteins to evaluate the severity of fMLP-induced ALI and the type of tissue damage in rats. In vitro experiments included evaluations of fMLP-induced damage on HPMVEC using cell activity assays, assessments of inflammatory and oxidative stress factors, measurements of ferroptosis-related proteins, endothelial barrier function assays, and examination of the key role of FPR2 in fMLP-induced ALI. We also assessed the protective effect of MOTS-c and investigated its mechanism on the fMLP-induced ALI in vivo and in vitro. RESULTS: Results from both in vitro and in vivo experiments demonstrate that fMLP promotes the expression of inflammatory and oxidative stress factors, activates ferroptosis and disrupts the vascular endothelial barrier, ultimately contributing to the development and progression of ALI. Mechanistically, ferroptosis mediated by FPR2 plays a key role in fMLP-induced injury, and the Nrf2 and MAPK pathways are involved in this process. Knockdown of FPR2 and inhibition of ferroptosis can attenuate ALI induced by fMLP. Moreover, MOTS-c could protect the vascular endothelial barrier function by inhibiting ferroptosis and suppressing the expression of inflammatory and oxidative stress factors through Nrf2 and MAPK pathways, thereby alleviating fMLP-induced ALI. CONCLUSION: Overall, fMLP disrupts the vascular endothelial barrier through FPR2-mediated ferroptosis, leading to the development and progression of ALI. MOTS-c demonstrates potential as a protective treatment against ALI by alleviating the damage induced by fMLP.


Subject(s)
Acute Lung Injury , Ferroptosis , Humans , Animals , Rats , NF-E2-Related Factor 2 , Peptides/pharmacology , Peptides/therapeutic use , Acute Lung Injury/chemically induced , Acute Lung Injury/drug therapy , Mitochondria , Lipopolysaccharides , Receptors, Formyl Peptide , Receptors, Lipoxin
20.
Heart Lung ; 65: 72-77, 2024.
Article in English | MEDLINE | ID: mdl-38432040

ABSTRACT

BACKGROUND: Studies have proved that low albumin level is associated with increased mortality in most diseases, such as chronic kidney disease and hepatic cirrhosis. However, the relationship between albumin and all-cause death in heart failure patients in China is still unclear. OBJECTIVES: We aimed to investigate the association between albumin level and 28-day mortality in Chinese hospitalized patients with NYHA IV heart failure. METHODS: A total of 2008 Chinese patients were included. The correlation between serum albumin level and mortality was tested using a cox proportional hazards regression model. The smooth curve fitting was used to identify non-linear relationships between serum albumin and mortality. The Forest plot analysis was used to assess the association between albumin and 28-day mortality in different groups. RESULTS: Compared with patients with NYHA II-III, patients with NYHA IV had lower albumin level and higher mortality within 28 days. The albumin on admission was independently and inversely associated with the endpoint risk, which remained significant (hazard ratio: 0.80; 95 % confidence interval: 0.66 to 0.96; p = 0.0196) after multivariable adjustment. The smooth curve fitting showed with the increase of albumin, the mortality within 28 days would decrease. A subgroup analysis found that the inverse association between the albumin level and risk of the mortality was consistent across the subgroup stratified by possible influence factors. CONCLUSION: Serum albumin level is negatively associated with 28-day mortality in hospitalized heart failure patients within NYHA IV in China, which can be used as an independent predictor.


Subject(s)
Heart Failure , Serum Albumin , Humans , Prognosis , Cause of Death , Proportional Hazards Models
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