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1.
Food Chem ; 400: 133998, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36055141

RESUMO

Colostrum is essential for immune system development and has a protective role for infants in early life. However, the lipid compositions of human and ewe colostra have not been characterized. We hypothesized that lipidomics can be used to compare lipids in two mammalian colostra. Herein, 1004 lipids assigned to 26 subclasses were identified in both human and ewe colostra using a quantitative lipidomics approach. In total, 173 significantly different lipids (SDLs) were investigated (variable importance in projection > 1.1, fold change (FC) ≥ 2 or ≤0.5, and P < 0.0001). Four potential lipid biomarkers, namely, DG (19:0/18:0), TG (10:0/15:0/16:0), FFA (22:0), and TG (18:1/24:1/18:2), were selected from the 173 SDLs based on FC values. These different lipids were involved in 44 metabolic pathways, of which sphingolipid metabolism and glycerophospholipid metabolism were the major pathways. Our results improve the understanding of the differences between human and ewe colostra lipids.


Assuntos
Colostro , Lipidômica , Animais , Biomarcadores/metabolismo , Colostro/metabolismo , Feminino , Glicerofosfolipídeos/metabolismo , Humanos , Metabolismo dos Lipídeos , Lipídeos , Mamíferos , Gravidez , Ovinos , Esfingolipídeos
2.
BMC Plant Biol ; 22(1): 144, 2022 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-35337273

RESUMO

Sophora davidii is an important plant resource in the karst region of Southwest China, but S. davidii plant-height mutants are rarely reported. Therefore, we performed phenotypic, anatomic structural, transcriptomic and metabolomic analyses to study the mechanisms responsible for S. davidii plant-height mutants. Phenotypic and anatomical observations showed that compared to the wild type, the dwarf mutant displayed a significant decrease in plant height, while the tall mutant displayed a significant increase in plant height. The dwarf mutant cells were smaller and more densely arranged, while those of the wild type and the tall mutant were larger and loosely arranged. Transcriptomic analysis revealed that differentially expressed genes (DEGs) involved in cell wall biosynthesis, expansion, phytohormone biosynthesis, signal transduction pathways, flavonoid biosynthesis and phenylpropanoid biosynthesis were significantly enriched in the S. davidii plant-height mutants. Metabolomic analysis revealed 57 significantly differential metabolites screened from both the dwarf and tall mutants. A total of 8 significantly different flavonoid compounds were annotated to LIPID MAPS, and three metabolites (chlorogenic acid, kaempferol and scopoletin) were involved in phenylpropanoid biosynthesis and flavonoid biosynthesis. These results shed light on the molecular mechanisms of plant height in S. davidii mutants and provide insight for further molecular breeding programs.


Assuntos
Sophora , Transcriptoma , Perfilação da Expressão Gênica , Metabolômica , Reguladores de Crescimento de Plantas/metabolismo , Sophora/genética , Sophora/metabolismo
3.
Artigo em Inglês | MEDLINE | ID: mdl-36421062

RESUMO

We report herein the synthesis of a stable plumbylone (3) by reduction of a bromodigermylplumbylene (2) with 2.2 equiv. of potassium graphite (KC8). The molecular structure of 3 was established by a single-crystal X-ray diffraction study and features a two-coordinated Pb center with an acute Ge-Pb-Ge bond angle. Computational studies showed that this complex (3) possesses a singlet electronic ground state with a Pb(0) center. Its high thermal stability can be most likely ascribed to the delocalization of π electrons over the Ge-Pb-Ge moiety. A preliminary reactivity study demonstrates that complex 3 can deliver Pb(0) atoms to an organic azide producing a tetrameric imido complex [(PbNDipp)4] (Dipp = 2,6- iPr-C6H3, 4) and perform a metathesis reaction with GeCl2·dioxane to produce a bis(germylene)-stabilized germylone (5), highlighting the synthetic utility of 3.

4.
Brain Behav ; : e2825, 2022 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-36423257

RESUMO

BACKGROUND: Patients with Parkinson's disease (PD) present various responsiveness to levodopa, but the cause of such differences in levodopa responsiveness is unclear. Previous studies related the damage of brain white matter (WM) to levodopa responsiveness in PD patients, but no study investigated the relationship between the structural brain network change in PD patients and their levodopa responsiveness. METHODS: PD patients were recruited and evaluated using the Unified Parkinson's Disease Rating Scale (UPDRS). Each patient received a diffusion tensor imaging (DTI) scan and an acute levodopa challenge test. The improvement rate of UPDRS-III was calculated. PD patients were grouped into irresponsive group (improvement rate < 30%) and responsive group (improvement rate ≥ 30%). Tract-based spatial statistics (TBSS), deterministic tracing (DT), region of interest (ROI) analysis, and automatic fiber identification (AFQ) analyses were performed. The structural brain network was also constructed and the topological parameters were calculated. RESULTS: Fifty-four PD patients were included. TBSS identified significant differences in fractional anisotropy (FA) values in the corpus callosum and other regions of the brain. DT and ROI analysis of the corpus callosum found a significant difference in FA between the two groups. Graph theory analysis showed statistical differences in global efficiency, local efficiency, and characteristic path length. CONCLUSION: PD patients with poor responsiveness to levodopa had WM damage in multiple brain areas, especially the corpus callosum, which might cause disruption of information integration of the structural brain network.

5.
Front Microbiol ; 13: 1040846, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36406423

RESUMO

Diabetes-specific microvascular disease is a leading cause of blindness, renal failure and nerve damage. Epidemiological data demonstrated that the high morbidity of T2DM occurs as a result of obesity and gradually develops into serious complications. To date, the mechanisms that underlie this observation are still ill-defined. In view of the effect of obesity on the gut microflora, Leprdb/db mice underwent antibiotic treatment and microbiota transplants to modify the gut microbiome to investigate whether microbes are involved in the development of diabetic nephropathy (DN) and/or diabetic retinopathy (DR). The mouse feces were collected for bacterial 16S ribosomal RNA gene sequencing. Cytokines including TNF-α, TGF-ß1, IFN-γ, IL-1ß, IL-6, IL-17A, IL-10, and VEGFA were detected by enzyme-linked immunosorbent assay (ELISA), flow cytometry, real-time PCR and immunofluorescent assay. Eyes and kidney were collected for histopathological assay. Intestinal permeability was also detected using Evans Blue. The results showed that obesity influenced metabolic variables (including fast/fed glucose, insulin, and triglyceride), retinopathy and nephropathy, and the gut microbiota. Obesity mainly reduced the ratio of Bacteroidetes/Firmicutes and influenced relative abundance of Proteobacteria, Actinobacteria, and Spirochetes. Obesity also increased intestinal permeability, metabolic endotoxemia, cytokines, and VEGFA. Microbiota transplants confirm that obesity aggravates retinopathy and nephropathy through the gut microbiota. These findings suggest that obesity exacerbates retinopathy and nephropathy by inducing gut microbiota dysbiosis, which further enhanced intestinal permeability and chronic low-grade inflammation.

6.
J Comput Chem ; 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36377670

RESUMO

Traditional π-covalent interactions have been proved in the non-metal halogen bond adducts formed by chloride and halogenated triphenylamine-based radical cations. In this study, we have rationally designed two metal-involving halogen bond adducts with π-covalency property, such as [L1-Pd···I-PTZ]+ (i.e., 1) and [L2-Pd···I-PTZ]+ (i.e., 2), in which the square-planar palladium complexes serve as halogen bond acceptor and 3,7-diiodo-10H-phenothiazine radical cation (i.e., [I-PTZ]•+ ) acts as halogen bond donor. Noncovalent interaction analysis and quantum theory of atoms in molecules analysis revealed that there are notable halogen bond interactions along the Pd···I direction without genuine chemical bond formed in both designed adducts. Energy decomposition analysis together with natural orbital for chemical valence calculations were performed to gain insight into their bonding nature, which demonstrated the presence of remarkable π-covalent interactions and σ-covalent interactions in both 1 and 2. We therefore proposed a new strategy for building the metal-involving halogen bonds with π-covalency property, which will help the further development of new types of halogen bonds.

7.
Medicine (Baltimore) ; 101(44): e31530, 2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36343041

RESUMO

Little is known about the association between serum alkaline phosphatase (ALP) levels and postoperative cognitive dysfunction (POCD) after general anesthesia. Thus, we investigated the association of serum ALP levels with POCD in patients who underwent surgery with general anesthesia in a retrospective cohort study. We retrospectively collected data from patients who underwent surgery with general anesthesia between May 2016 and June 2020. Serum ALP activity was detected using a p-nitrophenyl phosphate assay. Pre-and postoperative cognitive function were evaluated using the Chinese version of the Mini-Mental State Examination. Univariate and multivariate logistic regression were used to explore the effect of ALP on cognitive function. The incidence of POCD was 13.5%. Compared with the control group, the POCD group had higher ALP levels. The neuropsychological test results suggested that the scores of most items were lower in the POCD group than in the non-POCD group. Univariate logistic regression indicated that increased ALP levels were significantly associated with cognitive dysfunction (odds ratio = 1.15, 95% confidence interval: 1.13-1.18, P = .000). Multivariate regression showed that elevated ALP was still associated with POCD after adjusting for confounding factors (odds ratio = 1.16, 95% confidence interval: 1.13-1.18, P = .000). The spline regression model indicated the dose-response associations between ALP level and POCD risk (P for nonlinear trend < .001). Our study indicated that elevated serum ALP was an independent predictive factor of POCD at the 3-month follow-up. The occurrence of POCD could be associated with inflammatory status.


Assuntos
Disfunção Cognitiva , Complicações Cognitivas Pós-Operatórias , Humanos , Estudos Retrospectivos , Fosfatase Alcalina , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/diagnóstico , Anestesia Geral/métodos , Complicações Pós-Operatórias/diagnóstico , Testes Neuropsicológicos
8.
Int J Mol Sci ; 23(21)2022 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-36362450

RESUMO

Rice is an important food crop all over the world. It can be infected by the rice blast fungus Magnaporthe oryzae, which results in a significant reduction in rice yield. The infection mechanism of M. oryzae has been an academic focus for a long time. It has been found that G protein, AMPK, cAMP-PKA, and MPS1-MAPK pathways play different roles in the infection process. Recently, the function of TOR signaling in regulating cell growth and autophagy by receiving nutritional signals generated by plant pathogenic fungi has been demonstrated, but its regulatory mechanism in response to the nutritional signals remains unclear. In this study, a yeast amino acid permease homologue MoGap1 was identified and a knockout mutant of MoGap1 was successfully obtained. Through a phenotypic analysis, a stress analysis, autophagy flux detection, and a TOR activity analysis, we found that the deletion of MoGap1 led to a sporulation reduction as well as increased sensitivity to cell wall stress and carbon source stress in M. oryzae. The ΔMogap1 mutant showed high sensitivity to the TOR inhibitor rapamycin. A Western blot analysis further confirmed that the TOR activity significantly decreased, which improved the level of autophagy. The results suggested that MoGap1, as an upstream regulator of TOR signaling, regulated autophagy and responded to adversities such as cell wall stress by regulating the TOR activity.


Assuntos
Magnaporthe , Oryza , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Oryza/metabolismo , Autofagia/genética , Saccharomyces cerevisiae/metabolismo , Sistemas de Transporte de Aminoácidos/metabolismo , Doenças das Plantas/genética , Doenças das Plantas/microbiologia
9.
Org Lett ; 24(45): 8277-8282, 2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36318227

RESUMO

The methodology for the synthesis of fluorene-based atropisomers was developed via the strategy of aromatic ring formation. By this strategy, an efficient benzannulation of indene-based diene with benzoylacetonitrile divergently promoted by DABCO and a chiral organocatalyst was established, and various atropisomeric fluorene-based skeletons were generated in good yields, which not only provide a new strategy for the construction of atropisomeric biaryls but also offer a new member to the atropisomeric family.

10.
Eur J Pharmacol ; 937: 175364, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36336012

RESUMO

BACKGROUND: Activation of the NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome contributes to heart failure (HF) pathogenesis. However, the effect of NLRP3 inhibition on ß-adrenergic receptor agonist-induced HF remains unknown. Here, we evaluated the role of MCC950, a selective NLRP3 inhibitor, in isoproterenol (ISO)-induced cardiac dysfunction. METHODS: Mice were administered ISO (30 mg/kg/day) for 14 days with or without MCC950 (10 mg/kg) injection every other day. Cardiac function and the extent of hypertrophy and fibrosis were measured by echocardiography, HE and Masson trichrome staining, respectively. Immunohistochemistry, quantitative real-time PCR and Western blotting were performed to investigate the impact of MCC950 on ISO-induced cardiac dysfunction. The levels of oxidative stress and cell senescence were detected in H9C2 cells to explore the mechanism of MCC950 on ISO-induced myocardial injury in vitro. RESULTS: We found that the NLRP3 inflammasome was significantly activated in response to ISO treatment in mice. Selective inhibition of the NLRP3 inflammasome by MCC950 ameliorated cardiac fibrosis, hypertrophy and inflammation in ISO-treated mice, ultimately improving heart function. Furthermore, MCC950 significantly inhibited ISO-induced oxidative stress in the myocardium, accompanied by increased superoxide dismutase 2 (SOD2) and nuclear factor erythroid 2-related factor 2 (Nrf2) protein. In addition, MCC950 attenuated cardiomyocyte death and senescence in ISO-treated H9C2 cells, which was attributed to the decreased oxidative stress. CONCLUSION: NLRP3 inhibition by MCC950 ameliorated ISO-induced cardiac dysfunction by inhibiting cardiomyocyte senescence and oxidative stress. Therefore, inhibition of the NLRP3 inflammasome may be a potential therapeutic strategy for preventing cardiac dysfunction, especially age-related HF.


Assuntos
Cardiopatias , Inflamassomos , Camundongos , Animais , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Isoproterenol , Miócitos Cardíacos/metabolismo , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Sulfonas/farmacologia , Sulfonas/uso terapêutico , Furanos/farmacologia , Furanos/uso terapêutico , Cardiopatias/tratamento farmacológico , Hipertrofia/tratamento farmacológico
11.
Biomaterials ; 291: 121901, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36356473

RESUMO

Diabetes has been associated with postoperative complications, such as increased risk of tissue infection and impaired tissue repair caused by destabilization of hypoxia-inducible factor-1α (HIF-1α). Consequently, it is imperative to fabricate anti-bacterial and pro-regenerative small-diameter vascular grafts for treating cardiovascular disease in diabetic patients. Herein, we developed electrospun cobalt ion (Co2+)-loaded poly (ε-caprolactone) (PCL) microfiber vascular grafts (PCL-Co grafts). The released Co2+ significantly increased the stabilization of HIF-1α in high-glucose (HG)-treated HUVECs (HG-HUVECs) and macrophages (HG-macrophages). This resulted in enhanced cell migration, nitric oxide production, and secretion of bioactive factors by HG-HUVECs, and polarization of HG-macrophages toward M2 phenotypes in vitro. The Co2+ also conferred anti-bacterial properties to the grafts, while not perturbing the inherent anti-bacterial activities of HG-macrophages. Following abdominal artery implantation into type 2 diabetes mellitus (T2DM) rats, PCL-Co grafts were evaluated for performance in infection (grafts pre-contaminated with Staphylococcus aureus) and prophylaxes models (grafts alone). PCL-Co grafts prevented the incidence of subsequent infection in prophylaxes model and effectively inhibited the bacterial growth in the infection model. PCL-Co grafts also significantly enhanced cellularization, vascularization, endothelialization, contractile SMC regeneration and macrophages polarization in both models. Collectively, PCL-Co grafts exhibited the potential to combat infection and improve tissue regeneration under diabetes conditions.


Assuntos
Cobalto , Diabetes Mellitus Tipo 2 , Ratos , Animais , Poliésteres , Prótese Vascular , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico
12.
Cell Signal ; 101: 110517, 2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36332797

RESUMO

Colorectal cancer (CRC) continues to represent one of the major causes of cancer-related mortality and morbidity. MicroRNAs (miRNAs) are confirmed to be involved in modulating substential biological processes by affecting the expression of targeted genes, including carcinogenesis. In the present study, the expression pattern and functional roles of microRNA-15a-5p (miR-15a-5p) in CRC cells were investigated. The data from TCGA database indicated that miR-15a-5p is highly expressed in CRC tissues. Moreover, ectopic expression of miR-15a-5p facilitated the proliferation, migration, and invasion of CRC cells. Furthermore, bioinformatic analysis combinating with dual-luciferase assay revealed that SIRT4 acts as a crucial target of miR-15a-5p. Accordingly, overexpression of SIRT4 suppresses the miR-15a-5p-mediated enhancement in the proliferation, migration, and invasion of CRC cells, while the opposite phenotypes were observed after inhibition of SIRT4. Moreover, we further revealed that miR-15a-5p restrained the expression of SIRT4 to exacerbate the malignant phenotypes by modulating STAT3/TWIST1 and PETN/AKT signaling in CRC cells. Alternatively, inhibition of the miR-15a-5p/SIRT4 axis enhanced the chemosensitivity of 5-fluorouracil- and oxaliplatin-resistant HCT116 cells. Altogether, our evidence suggests that miR-15a-5p plays an essential role in promoting the proliferation, migration, and chemoresistance of CRC cells via targeting SIRT4 to modulate STAT3/TWIST1 and PETN/AKT signaling, which may serve as a promising therapeutic target for CRC therapy.

13.
Materials (Basel) ; 15(22)2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36431674

RESUMO

Silicon carbide (SiC) is a wide-bandgap (WBG) semiconductor material, and its preparation process has strict requirements on the purity of raw materials. A self-developed medium-frequency induction heating furnace was used to carry out powder heat treatment and purification experiments on SiC powder to improve the purity of the powder. Samples with 3.5N purity were analyzed using XRD and GDMS characterization methods. It was found that under conditions of high-temperature (2200 °C) and long-time (50 h) processing, the impurity removal effect was quite good, but the powder loss was as high as 53.42%. The powder loss during the low-temperature (less than 2050 °C) and short-time process was less than 1.5%, but the purification effect was not substantial. After a prolonged processing time, the purification effect of low-temperature heat treatment conditions was improved, but the powder loss was also increased to 30%. In contrast, segmented purification processing at a low temperature in the early stage and a high temperature in the later stage achieved a good purification effect. On the premise of maintaining the utilization rate of raw materials, a 5N-purity SiC source was successfully prepared. The test results show that the contents of free Si, free C and free oxygen impurities were reduced to less than 0.01%, and the contents of Al, B, Fe, Mg, Na, Ti and other impurities were less than 1.15 ppm, which is close to the ppb level.

14.
Injury ; 53(12): 3920-3929, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36357245

RESUMO

Mesenchymal stem cells (MSCs) play a key role in wound healing, and the advantages of pretreated MSCs in wound healing have previously been reported. In the present study, we investigated the impact of LPS pretreated human adipose-derived MSCs on skin wound healing in diabetic rats. We found that some improvements occurred through improving angiogenesis. Then, we scrutinized the impact of lipopolysaccharide (LPS) treatment on human adipose-derived MSCs in a high-glucose (HG) medium, as an in vitro diabetic model. In vivo findings revealed significant improvements in epithelialization and angiogenesis of diabetic wounds which received LPS pre-MSCs. Particularly, LPS pre-MSCs-treated diabetic wounds reached considerably higher percentages of wound closure. Also, the granulation tissue of these wounds had higher pronounced epithelialization and more vascularization compared with PBS-treated and MSCs-treated diabetic ones by CD31, VEGF, CD90, collagen 1, and collagen 3 immunostaining. Western-blots analyses indicated that LPS pre-MSCs led to the upregulation of vascular endothelial growth factor (VEGF) and DNMT1. In addition, significantly higher cell viability (proliferation/colonie), and elevated VEGF and DNMT1 protein expression were observed when MSCs were treated with LPS (10 ng/ml, 6 h) in HG culture media. Based on these findings, it is suggested that LPS pre-MSCs could promote wound repair and skin regeneration, in some major processes, via the improvement of cellular behaviors of MSCs in the diabetic microenvironment. The beneficial advantages of LPS treated with mesenchymal stem cells on wound healing may lead to establishing a novel approach as an alternative therapeutic procedure to cure chronic wounds in diabetic conditions.


Assuntos
Diabetes Mellitus Experimental , Células-Tronco Mesenquimais , Ratos , Humanos , Animais , Lipopolissacarídeos/farmacologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Diabetes Mellitus Experimental/terapia , Diabetes Mellitus Experimental/metabolismo , Cicatrização , Colágeno/metabolismo
15.
BMC Oral Health ; 22(1): 481, 2022 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-36357898

RESUMO

The environment of healthcare institutes (HCIs) potentially affects the internal microecology of medical workers, which is reflected not only in the well-studied gut microbiome but also in the more susceptible oral microbiome. We conducted a prospective cross-sectional cohort study in four hospital departments in Central China. Oropharyngeal swabs from 65 healthcare workers were collected and analyzed using 16S rRNA gene amplicon sequencing. The oral microbiome of healthcare workers exhibited prominent deviations in diversity, microbial structure, and predicted function. The coronary care unit (CCU) samples exhibited robust features and stability, with significantly higher abundances of genera such as Haemophilus, Fusobacterium, and Streptococcus, and a lower abundance of Prevotella. Functional prediction analysis showed that vitamin, nucleotide, and amino acid metabolisms were significantly different among the four departments. The CCU group was at a potential risk of developing periodontal disease owing to the increased abundance of F. nucleatum. Additionally, oral microbial diversification of healthcare workers was related to seniority. We described the oral microbiome profile of healthcare workers in different clinical scenarios and demonstrated that community diversity, structure, and potential functions differed markedly among departments. Intense modulation of the oral microbiome of healthcare workers occurs because of their original departments, especially in the CCU.


Assuntos
Bactérias , Microbiota , Humanos , RNA Ribossômico 16S/genética , Estudos Transversais , Bactérias/genética , Estudos Prospectivos , Pessoal de Saúde
16.
Nat Chem ; 2022 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-36344822

RESUMO

Carbynes (R-[Formula: see text]), species that bear a monovalent carbon atom with three non-bonding valence electrons, are important intermediates and potentially useful in organic synthetic chemistry. However, free species of the type R-[Formula: see text] of any group 14 element (E) have eluded isolation in the condensed phase due to their high reactivity. Here we report the isolation, characterization and reactivity of a crystalline germylyne radical by using a sterically hindered hydrindacene ligand. The germylyne radical bears an essentially one-coordinate germanium atom as shown by single-crystal X-ray diffraction analysis. Electron paramagnetic resonance spectroscopic studies and theoretical calculations show that the germylyne radical features a doublet ground state, and the three non-bonding valence electrons at the germanium atom contribute to the lone pair of electrons as the highest occupied molecular orbital-3 and one unpaired electron as the singly occupied molecular orbital.

17.
Neurol Sci ; 2022 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-36445542

RESUMO

BACKGROUND AND PURPOSE: Preclinical studies have shown that metformin has neuroprotective actions in stroke. However, the optimal treatment timing and duration remain unknown. Herein, we examined the efficacy of metformin treatment on prognosis in acute ischemic stroke (AIS) patients, and assessed the optimal treatment timing and duration. METHODS: AIS patients with type 2 diabetes mellitus were retrospectively enrolled. Patients were grouped into those who never received metformin (MET - group), those who received metformin continuously before stroke and after admission (pre-stroke + /post-stroke + group), those who only received metformin before stroke onset (pre-stroke + /post-stroke - group), and those who only received metformin after admission (pre-stroke - /post-stroke + group). The all MET + group represents the sum of the three metformin treatment groups. The efficacy outcome was the 90-day modified Rankin Scale (mRS) score. RESULTS: In total, 309 eligible patients were included (MET - [N = 130], pre-stroke + /post-stroke + [N = 94], pre-stroke + /post-stroke - [N = 30], pre-stroke - /post-stroke + [N = 55]; all MET + [N = 179]). The all MET + group had a trend toward a lower 90-day mRS score compared with that in the MET - group (1 [0-2] vs 1 [0-3], unadjusted odds ratio [OR] = 0.652, P = 0.041; adjusted OR = 0.752, P = 0.218). In the three metformin treatment groups, only the pre-stroke + /post-stroke + group had a significantly lower 90-day mRS score (1 [0-1] vs 1 [0-3], adjusted OR = 0.497, 95%CI = 0.289-0.854; P = 0.011) and higher proportion of mRS score 0-1 (78.7% vs. 61.5%, adjusted OR = 2.278, 95%CI = 1.108-4.680; P = 0.025) than the MET - group. CONCLUSION: AIS patients with type 2 diabetes mellitus who receive continuous metformin treatment before stroke onset and after admission have improved functional outcome at 90 days.

18.
Front Immunol ; 13: 996469, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36211343

RESUMO

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) characterized by destruction of the myelin sheath structure. The loss of myelin leads to damage of a neuron's axon and cell body, which is identified as brain lesions on magnetic resonance image (MRI). The pathogenesis of MS remains largely unknown. However, immune mechanisms, especially those linked to the aberrant lymphocyte activity, are mainly responsible for neuronal damage. Th1 and Th17 populations of lymphocytes were primarily associated with MS pathogenesis. These lymphocytes are essential for differentiation of encephalitogenic CD8+ T cell and Th17 lymphocyte crossing the blood brain barrier and targeting myelin sheath in the CNS. B-lymphocytes could also contribute to MS pathogenesis by producing anti-myelin basic protein antibodies. In later studies, aberrant function of Treg and Th9 cells was identified as contributing to MS. This review summarizes the aberrant function and count of lymphocyte, and the contributions of these cell to the mechanisms of MS. Additionally, we have outlined the novel MS therapeutics aimed to amend the aberrant function or counts of these lymphocytes.


Assuntos
Encefalomielite Autoimune Experimental , Esclerose Múltipla , Animais , Sistema Nervoso Central , Esclerose Múltipla/etiologia , Esclerose Múltipla/terapia , Bainha de Mielina , Células Th17
19.
Front Immunol ; 13: 954653, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36189204

RESUMO

Intratumoral copper levels are closely associated with immune escape from diverse cancers. Cuproptosis-related lncRNAs (CRLs), however, have an unclear relationship with hepatocellular carcinoma (HCC). Gene expression data from 51 normal tissues and 373 liver cancer tissues from the Cancer Genome Atlas (TCGA) database were collected and analyzed. To identify CRLs, we employed differentially expressed protein-coding genes (DE-PCGs)/lncRNAs (DE-lncRNAs) analysis, Kaplan-Meier (K-M) analysis, and univariate regression. By univariate and Lasso Cox regression analyses, we screened 10 prognosis-related lncRNAs. Subsequently, five CRLs were identified by multivariable Cox regression analysis to construct the prognosis model. This feature is an independent prognostic indicator to forecast overall survival. According to Gene Set Variation Analysis (GSVA) and Gene Ontology (GO), both immune-related biological processes (BPS) and pathways have CRL participation. In addition, we found that the characteristics of CRLs were associated with the expression of the tumor microenvironment (TME) and crucial immune checkpoints. CRLs could predict the clinical response to immunotherapy based on the studies of tumor immune dysfunction and rejection (TIDE) analysis. Additionally, it was verified that tumor mutational burden survival and prognosis were greatly different between high-risk and low-risk groups. Finally, we screened potential sensitive drugs for HCC. In conclusion, this study provides insight into the TME status in patients with HCC and lays a basis for immunotherapy and the selection of sensitive drugs.


Assuntos
Fenômenos Biológicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , RNA Longo não Codificante , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Cobre/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Prognóstico , RNA Longo não Codificante/metabolismo , Microambiente Tumoral/genética
20.
Gastrointest Endosc ; 2022 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-36252870

RESUMO

BACKGROUND AND AIMS: The prevalence of high-risk varices (HRV) is low among compensated cirrhotic patients undergoing esophagogastroduodenoscopy (EGD). Our study aimed to identify a novel machine learning-based model, named ML EGD, for ruling out HRV and avoiding unnecessary EGDs in patients with compensated cirrhosis. METHODS: An international cohort from 17 institutions from China, Singapore, and India were enrolled (CHESS2001, NCT04307264). The variables with the top three importance scores (liver stiffness, platelet count, and total bilirubin) were selected by shapley additive explanation and inputted into light gradient boosting machine algorithm to develop ML EGD for identification of HRV. Furthermore, we built a web-based calculator of ML EGD and it was free with open access at http://www.pan-chess.cn/calculator/MLEGD_score. Spared EGDs and the rates of missed HRV were used to assess the efficacy and safety for varices screening. RESULTS: A total of 2,794 patients were enrolled. Of them, 1,283 patients in a real-world cohort from one university hospital in China were to develop and internally validate the performance of ML EGD for varices screening. They were randomly assigned into the training (n = 1154) and validation (n = 129) cohorts with a ratio of 9:1. In the training cohort, ML EGD spared 607 (52.6%) unnecessary EGDs with a missed HRV rate of 3.6%. In the validation cohort, ML EGD spared 75 (58.1%) EGDs with a missed HRV rate of 1.4%. To externally test the performance of ML EGD, 966 patients from 14 university hospitals in China (test cohort 1) and 545 from two hospitals in Singapore and India (test cohort 2) comprised two test cohorts. In the test cohort 1, ML EGD spared 506 (52.4%) EGDs with a missed HRV rate of 2.8%. In the test cohort 2, ML EGD spared 224 (41.1%) EGDs with a missed HRV rate of 3.1%. Comparing with Baveno VI criteria, ML EGD spared more screening EGDs in all cohorts (training cohort, 52.6% vs 29.4%; validation cohort, 58.1% vs 44.2%; test cohort 1, 52.4% vs 26.5%; test cohort 2, 41.1% vs 21.1%) (p < 0.001). CONCLUSIONS: We identified a novel model based on liver stiffness, platelet count, and total bilirubin, named ML EGD, as a free web-based calculator. ML EGD could efficiently help rule out HRV and avoid unnecessary EGDs in patients with compensated cirrhosis.

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