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1.
Sci Rep ; 14(1): 13412, 2024 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-38862553

RESUMO

Previous studies have reported that the significant association between serum calcium and mortality substantially in patients, especially among those with intensive care unit (ICU). And In diabetes mellitus, congestive heart failure (CHF) is a significant comorbidity. We aim to evaluate the association between serum calcium levels and in-hospital mortality among patients with diabetes and congestive heart failure. The participants in this study were extracted from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. To scrutinize potential associations between serum calcium levels and in-hospital mortality, a comprehensive analysis encompassing multivariate logistic regression, cubic spline function model, threshold effect analysis, and subgroup analysis was performed. This retrospective cohort study encompassed 7063 patients, among whom the in-hospital mortality stood at 12.2%. In the multivariate logistic regression, adjusted odds ratios (ORs) were contrasted with the reference category Q6 (8.8-9.1 mg/dL) for serum calcium levels and in-hospital mortality. The adjusted ORs for Q1 (≤ 7.7 mg/dL), Q2 (7.7-8 mg/dL), and Q7 (≥ 9.1 mg/dL) were 1.69 (95% CI 1.17-2.44, p = 0.005), 1.62 (95% CI 1.11-2.36, p = 0.013), and 1.57 (95% CI 1.1-2.24, p = 0.012) respectively. The dose-response analysis uncovered a U-shaped relationship between serum calcium levels and in-hospital mortality in diabetic patients with heart failure. Subgroup analyses confirmed result stability notwithstanding the influence of diverse factors. Our investigation revealed a U-shaped correlation between serum calcium levels and in-hospital mortality in diabetes patients with congestive heart failure, pinpointing a significant inflection point at 9.05 mg/dL.


Assuntos
Cálcio , Diabetes Mellitus , Insuficiência Cardíaca , Mortalidade Hospitalar , Humanos , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/sangue , Feminino , Masculino , Idoso , Cálcio/sangue , Pessoa de Meia-Idade , Estudos Retrospectivos , Diabetes Mellitus/sangue , Diabetes Mellitus/mortalidade , Idoso de 80 Anos ou mais
2.
J Nutr Biochem ; : 109678, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38844080

RESUMO

The solute carrier family 25 member 1 (Slc25a1)-dependent mitochondrial citrate shuttle is responsible for exporting citrate from the mitochondria to the cytoplasm for supporting lipid biosynthesis and protein acetylation. Previous studies on Slc25a1 concentrated on pathological models. However, the importance of Slc25a1 in maintaining metabolic homeostasis under normal nutritional conditions remains poorly understood. Here, we investigated the mechanism of mitochondrial citrate shuttle in maintaining lipid metabolism homeostasis in male Nile tilapia (Oreochromis niloticus). To achieve the objective, we blocked the mitochondrial citrate shuttle by inhibiting Slc25a1 under normal nutritional conditions. Slc25a1 inhibition was established by feeding Nile tilapia with 250 mg/kg 1,2,3-benzenetricarboxylic acid hydrate for six weeks or intraperitoneal injecting them with dsRNA to knockdown slc25a1b for seven days. The Nile tilapia with Slc25a1 inhibition exhibited an obesity-like phenotype accompanied by fat deposition, liver damage and hyperglycemia. Moreover, Slc25a1 inhibition decreased hepatic citrate-derived acetyl-CoA, but increased hepatic triglyceride levels. Furthermore, Slc25a1 inhibition replenished cytoplasmic acetyl-CoA through enhanced acetate pathway, which led to hepatic triglycerides accumulation. However, acetate-derived acetyl-CoA caused by hepatic Slc25a1 inhibition did not activate de novo lipogenesis, but rather modified protein acetylation. In addition, hepatic Slc25a1 inhibition enhanced fatty acids esterification through acetate-derived acetyl-CoA, which increased Lipin1 acetylation and its protein stability. Collectively, our results illustrate that inhibiting mitochondrial citrate shuttle triggers lipid anabolic remodeling and results in lipid accumulation, indicating the importance of mitochondrial citrate shuttle in maintaining lipid metabolism homeostasis.

3.
Chem Commun (Camb) ; 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38845407

RESUMO

Herein, a novel strategy is presented for the photoinduced decarboxylative and dehydrogenative cross-coupling of a wide range of α-fluoroacrylic acids with hydrogermanes. This methodology provides an efficient and robust approach for producing various germylated monofluoroalkenes with excellent stereoselectivity within a brief photoirradiation period. The feasibility of this reaction has been demonstrated through gram-scale reaction, conversion of germylated monofluoroalkenes, and modification of complex organic molecules.

4.
Int J Ophthalmol ; 17(3): 537-544, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38721498

RESUMO

AIM: To identify the differential methylation sites (DMS) and their according genes associated with diabetic retinopathy (DR) development in type 1 diabetes (T1DM) children. METHODS: This study consists of two surveys. A total of 40 T1DM children was included in the first survey. Because no participant has DR, retina thinning was used as a surrogate indicator for DR. The lowest 25% participants with the thinnest macular retinal thickness were included into the case group, and the others were controls. The DNA methylation status was assessed by the Illumina methylation 850K array BeadChip assay, and compared between the case and control groups. Four DMS with a potential role in diabetes were identified. The second survey included 27 T1DM children, among which four had DR. The methylation patterns of the four DMS identified by 850K were compared between participants with and without DR by pyrosequencing. RESULTS: In the first survey, the 850K array revealed 751 sites significantly and differentially methylated in the case group comparing with the controls (|Δß|>0.1 and Adj.P<0.05), and 328 of these were identified with a significance of Adj.P<0.01. Among these, 319 CpG sites were hypermethylated and 432 were hypomethylated in the case group relative to the controls. Pyrosequencing revealed that the transcription elongation regulator 1 like (TCERG1L, cg07684215) gene was hypermethylated in the four T1DM children with DR (P=0.018), which was consistent with the result from the first survey. The methylation status of the other three DMS (cg26389052, cg25192647, and cg05413694) showed no difference (all P>0.05) between participants with and without DR. CONCLUSION: The hypermethylation of the TCERG1L gene is a risk factor for DR development in Chinese children with T1DM.

5.
Clin Nutr ; 43(6): 1544-1550, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38754306

RESUMO

Few prospective studies have investigated the joint effect of lifestyle factors and genetic susceptibility on the risk of irritable bowel syndrome (IBS). This study aims to evaluate the associations of lifestyle and genetic factors with incident IBS in the UK Biobank. We analyzed data from 481,057 participants (54% female) without prevalent IBS at enrollment in the UK Biobank. An overall healthy lifestyle was defined using six modifiable lifestyle factors, including smoking, body mass index (BMI), sleep duration, diet, physical activity, and alcohol consumption, and hence categorized into 'favorable', 'intermediate', and 'unfavorable' lifestyles. A Cox proportional hazard model was used to investigate the association between a healthy lifestyle and incident IBS. Furthermore, we constructed a polygenic risk score (PRS) for IBS and assessed whether lifestyle modified the effect of genetics on the development of IBS. During a median follow-up of 12.1 years, 8645 incident IBS were ascertained. Specifically, among the six modifiable lifestyle factors, adequate sleep demonstrates the greatest protective effect (hazard ratio [HR]: 0.72, 95% CI: 0.69,0.75) against IBS. Compared with a favorable lifestyle, an unfavorable lifestyle was associated with a 56% (95% CI: 46%-67%) increased risk of IBS (P = 8.99 × 10-40). The risk of incident IBS was 12% (95% CI: 4%-21%) higher among those at high genetic risk compared with those at low genetic risk (P = 0.005). When considering the joint effect of lifestyle and genetic susceptibility, the HR nearly doubled among individuals with high genetic risk and unfavorable lifestyle (HR: 1.80; 95% CI:1.51-2.15; P = 3.50 × 10-11) compared to those with low genetic risk and favorable lifestyle. No multiplicative or addictive interaction was observed between lifestyle and genetics. The findings from this study indicated that lifestyle and genetic factors were independently associated with the risk of incident IBS. All these results implicated a possible clinical strategy of lowering the incidence of IBS by advocating a healthy lifestyle.


Assuntos
Predisposição Genética para Doença , Síndrome do Intestino Irritável , Estilo de Vida , Humanos , Síndrome do Intestino Irritável/genética , Síndrome do Intestino Irritável/epidemiologia , Feminino , Masculino , Estudos Prospectivos , Pessoa de Meia-Idade , Incidência , Reino Unido/epidemiologia , Fatores de Risco , Adulto , Modelos de Riscos Proporcionais , Idoso , Sono/genética , Estilo de Vida Saudável , Dieta/estatística & dados numéricos
6.
Arch Insect Biochem Physiol ; 116(1): e22117, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38706214

RESUMO

More and more evidence shows that small noncoding RNAs (ncRNAs) play diverse roles in development, stress response and other cellular processes, but functional study of intermediate-size ncRNAs is still rare. Here, the expression profile of 16 intermediate-size ncRNAs in ovary and testis of silkworm Bombyx mori were analyzed. Twelve ncRNAs, including 5 small nucleolar RNAs (snoRNAs) and 7 unclassified ncRNAs, accumulated more in the testis than in the ovary of silkworm, especially Bm-163, Bm-51 and Bm-68. Four ncRNAs (including three orphan snoRNAs and one unclassified ncRNA) had higher expression level in the ovary than in the testis, especially Bm-86. Overexpression of the testis-enriched snoRNA Bm-68 in the female led to the accumulation of male-specific isoform of doublesex (BmdsxM) and increased the expression ratio of BmdsxM: BmdsxF. While overexpression of ovary-enriched snoRNA Bm-86 in the male decreased the expression ratio of BmdsxM: BmdsxF, indicating the roles of the two snoRNAs played in the alternative splicing of Bmdsx of silkworm, which will provide new clues for the functional study of snoRNAs in insects.


Assuntos
Processamento Alternativo , Bombyx , Proteínas de Ligação a DNA , Proteínas de Insetos , RNA Nucleolar Pequeno , Animais , Feminino , Masculino , Bombyx/genética , Bombyx/metabolismo , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Ovário/metabolismo , RNA Nucleolar Pequeno/genética , RNA Nucleolar Pequeno/metabolismo , Testículo/metabolismo
7.
Mol Divers ; 2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38762686

RESUMO

Monomethyl auristatin F (MMAF), a synthetic analogue of the natural compound dolastatin 10, has garnered significant attention in cancer research due to its high potency in vitro. While previous studies have focused on modifying the N-terminal extension of the amino group and the C-terminal modification of the carboxyl group, there has been limited exploration into modifying the P1 and P5 side chains. In this study, we substituted the valine residue at the P1 position with various natural or unnatural amino acids and introduced triazole functional groups at the P5 side chain. Compounds 11k and 18d exhibited excellent inhibition on tubulin. Additionally, compound 18d demonstrated enhanced cytotoxicity against HCT116 cells compared to the parent compound MMAF, suggesting its potential as a cytotoxic payload for further antibody-drug conjugates (ADCs) development.

8.
PLoS One ; 19(5): e0299522, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38696452

RESUMO

Hepatocellular carcinoma (HCC) is the most common primary liver cancer worldwide and no pharmacological treatment is available that can achieve complete remission of HCC. Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) is a recently identified HCC tumor suppressor gene which plays an important role in the development of HCC and its inactivation and reactivation has been shown to result in respectively HCC tumorigenesis and suppression. Small activating RNAs (saRNAs) have been used to achieve targeted activation of therapeutic genes for the restoration of their encoded protein through the RNAa mechanism. Here we designed and validated saRNAs that could activate LHPP expression at both the mRNA and protein levels in HCC cells. Activation of LHPP by its saRNAs led to the suppression of HCC proliferation, migration and the inhibition of Akt phosphorylation. When combined with targeted anticancer drugs (e.g., regorafenib), LHPP saRNA exhibited synergistic effect in inhibiting in vitro HCC proliferation and in vivo antitumor growth in a xenograft HCC model. Findings from this study provides further evidence for a tumor suppressor role of LHPP and potential therapeutic value of restoring the expression of LHPP by saRNA for the treatment of HCC.


Assuntos
Carcinoma Hepatocelular , Proliferação de Células , Pirofosfatase Inorgânica , Neoplasias Hepáticas , Humanos , Pirofosfatase Inorgânica/metabolismo , Pirofosfatase Inorgânica/genética , Proliferação de Células/efeitos dos fármacos , Animais , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/genética , Camundongos , Linhagem Celular Tumoral , Regulação para Cima/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Movimento Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Camundongos Nus
9.
Phytochemistry ; 224: 114163, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38815883

RESUMO

Stereochemical investigations on the twigs and leaves of Solanum erianthum afforded five pairs of lignanamide enantiomers and a previously undescribed phenolic amide (3). Particularly, two pairs of previously undescribed lignanamide racemates (1a/1b-2a/2b) represent the first case of natural products that feature an unreported 5/5-fused N/O-biheterocyclic core. Their structures, including the absolute configurations, were determined unambiguously by using spectroscopic analyses and electronic circular dichroism calculations. A speculative biogenetic pathway for 1-3 was proposed. Interestingly, these lignanamides exhibited enantioselective antiplasmodial activities against drug-sensitive Plasmodium falciparum 3D7 strain and chloroquine-resistant Plasmodium falciparum Dd2 strain, pointing out that chirality plays an important role in drug development.


Assuntos
Antimaláricos , Folhas de Planta , Plasmodium falciparum , Solanum , Plasmodium falciparum/efeitos dos fármacos , Antimaláricos/química , Antimaláricos/farmacologia , Antimaláricos/isolamento & purificação , Folhas de Planta/química , Solanum/química , Estereoisomerismo , Estrutura Molecular , Lignanas/química , Lignanas/farmacologia , Lignanas/isolamento & purificação , Amidas/química , Amidas/farmacologia , Amidas/isolamento & purificação , Relação Estrutura-Atividade , Testes de Sensibilidade Parasitária
10.
J Am Chem Soc ; 146(23): 15908-15916, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38809425

RESUMO

Efficient transformation of platform chemicals into key intermediates has been increasingly important for the pharmaceutical industry. The development of the catalytic reduction of abundant carboxylic acids with molecular hydrogen has been of both practical and theoretical value. We herein report the homogeneous hydrogenation of dicarboxylic acids with the strategy of desymmetrization. Using a rhodium/bisphosphine catalyst, one carboxyl group of meso-diacids was selectively reduced to yield chiral lactones with satisfactory enantioselectivity. This method provides a straightforward approach to produce chiral lactone intermediates for the manufacture of biotin, telaprevir, and other antivirus drugs. Both experimental and computational investigations were carried out, revealing a novel neighboring group coordination mechanism in the catalytic cycle.

11.
Biomaterials ; 309: 122613, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38759485

RESUMO

Vascular restenosis following angioplasty continues to pose a significant challenge. The heterocyclic trioxirane compound [1, 3, 5-tris((oxiran-2-yl)methyl)-1, 3, 5-triazinane-2, 4, 6-trione (TGIC)], known for its anticancer activity, was utilized as the parent ring to conjugate with a non-steroidal anti-inflammatory drug, resulting in the creation of the spliced conjugated compound BY1. We found that BY1 induced ferroptosis in VSMCs as well as in neointima hyperplasia. Furthermore, ferroptosis inducers amplified BY1-induced cell death, while inhibitors mitigated it, indicating the contribution of ferroptosis to BY1-induced cell death. Additionally, we established that ferritin heavy chain1 (FTH1) played a pivotal role in BY1-induced ferroptosis, as evidenced by the fact that FTH1 overexpression abrogated BY1-induced ferroptosis, while FTH1 knockdown exacerbated it. Further study found that BY1 induced ferroptosis by enhancing the NCOA4-FTH1 interaction and increasing the amount of intracellular ferrous. We compared the effectiveness of various administration routes for BY1, including BY1-coated balloons, hydrogel-based BY1 delivery, and nanoparticles targeting OPN loaded with BY1 (TOP@MPDA@BY1) for targeting proliferated VSMCs, for prevention and treatment of the restenosis. Our results indicated that TOP@MPDA@BY1 was the most effective among the three administration routes, positioning BY1 as a highly promising candidate for the development of drug-eluting stents or treatments for restenosis.


Assuntos
Ferroptose , Músculo Liso Vascular , Nanopartículas , Ferroptose/efeitos dos fármacos , Animais , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/citologia , Humanos , Nanopartículas/química , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Oxirredutases/metabolismo , Ferritinas
12.
Biomacromolecules ; 25(6): 3373-3383, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38713187

RESUMO

The control over secondary structure has been widely studied to regulate the properties of polypeptide materials, which is used to change their functions in situ for various biomedical applications. Herein, we designed and constructed enzyme-responsive polypeptides as gating materials for mesoporous silica nanoparticles (MSNs), which underwent a distorted structure-to-helix transition to promote the release of encapsulated drugs. The polypeptide conjugated on the MSN surface adopted a negatively charged, distorted, flexible conformation, covering the pores of MSN to prevent drug leakage. Upon triggering by alkaline phosphatase (ALP) overproduced by tumor cells, the polypeptide transformed into positively charged, α-helical, rigid conformation with potent membrane-penetrating capabilities, which protruded from the MSN surface to uncover the pores. Such a transition thus enabled cancer-selective drug release and cellular internalization to efficiently kill tumor cells. This study highlights the important role of chain flexibility in modulating the biological function of polypeptides and provides a new application paradigm for synthetic polypeptides with secondary-structure transition.


Assuntos
Liberação Controlada de Fármacos , Nanopartículas , Peptídeos , Dióxido de Silício , Humanos , Peptídeos/química , Nanopartículas/química , Dióxido de Silício/química , Doxorrubicina/química , Doxorrubicina/farmacologia , Fosfatase Alcalina/metabolismo , Fosfatase Alcalina/química , Preparações de Ação Retardada/química , Porosidade , Antineoplásicos/química , Antineoplásicos/farmacologia , Estrutura Secundária de Proteína
13.
J Am Chem Soc ; 146(19): 13306-13316, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38690945

RESUMO

Traditional superwettable membranes for demulsification of oil/water emulsions could not maintain their separation performance for long because of low demulsification capacity and surface fouling during practical applications. A charging membrane could repel the contaminants for a while, the charge of which would gradually be neutralized during the separation progress. Here, a superhydrophilic piezoelectric membrane (SPM) with sustained demulsification and antifouling capacity is proposed for achieving prolonged emulsion separation, which is capable of converting inherent pulse hydraulic filtration pressure into pulse voltage. A pulse voltage up to -7.6 V is generated to intercept the oil by expediting the deformation and coalescence of emulsified oil droplets, realizing the demulsification. Furthermore, it repels negatively charged oil droplets, avoiding membrane fouling. Additionally, any organic foulants adhering to the membrane undergo degradation facilitated by the generated reactive oxygen species. The separation data demonstrate a 98.85% efficiency with a flux decline ratio below 14% during a 2 h separation duration and a nearly 100% flux recovery of SPM. This research opens new avenues in membrane separation, environmental remediation, etc.

14.
World J Gastrointest Oncol ; 16(5): 2219-2224, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38764824

RESUMO

BACKGROUND: According to the latest report, colorectal cancer is still one of the most prevalent cancers, with the third highest incidence and mortality worldwide. Treatment of advanced rectal cancer with distant metastases is usually unsatisfactory, especially for mismatch repair proficient (pMMR) rectal cancer, which leads to poor prognosis and recurrence. CASE SUMMARY: We report a case of a pMMR rectal adenocarcinoma with metastases of multiple lymph nodes, including the left supraclavicular lymph node, before treatment in a 70-year-old man. He received full courses of chemoradiotherapy (CRT) followed by 4 cycles of programmed death 1 inhibitor Tislelizumab, and a pathologic complete response (pCR) was achieved, and the lesion of the left supraclavicular lymph node also disappeared. CONCLUSION: pMMR advanced rectal cancer with preserved intact distant metastatic lymph nodes may benefit from full-course CRT combined with immunotherapy.

15.
Angew Chem Int Ed Engl ; : e202405560, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38787342

RESUMO

Radical-involved multicomponent difunctionalization of 1,3-dienes has recently emerged as a promising strategy for rapid synthesis of valuable allylic compounds in one-pot operation. However, the expansion of radical scope and enantiocontrol remain two major challenges. Herein, we describe an unprecedented photoinduced copper-catalyzed highly enantioselective three-component radical 1,2-azidooxygenation of 1,3-dienes with readily available azidobenziodazolone reagent and carboxylic acids. This mild protocol exhibits a broad substrate scope, high functional group tolerance, and exceptional control over chemo-, regio- and enantioselectivity, providing practical access to diverse valuable azidated chiral allylic esters. Mechanistic studies imply that the chiral copper complex is implicated as a bifunctional catalyst in both the photoredox catalyzed azidyl radical generation and enantioselective radical C-O cross-coupling.

16.
J Rheumatol ; 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38749557

RESUMO

OBJECTIVE: Although previous studies have explored the association of drinking with gout risk, the dose-response relationship was uncertain and the evidence between subtypes of alcoholic beverages and gout risk was limited. METHODS: The weekly alcoholic beverage consumption in the United Kingdom Biobank (UKB) was collected and calculated. The Cox regression model was applied to assess the impact of alcohol drinking and its subtypes on gout risk by calculating the hazard ratio (HR) and 95% confidence interval (CI). Besides, the restricted cubic splines were used to estimate the dose-response relationship between alcoholic drinking and gout risk. To evaluate the robustness, we performed subgroup analysis across various demographic characteristics. RESULTS: During a mean follow-up period of 11.70 years, a total of 5,728 newly incident gout cases were diagnosed among 331,865 participants. We found that light alcohol drinking was linked to a slight decrease in gout incidence among females (HR, 0.78; 95% CI, 0.65 to 0.94, P=0.01), whereas it showed no significant association in males. Moreover, the dose-response relationship showed that light red wine and fortified wine could reduce the gout risk, while beer, champagne plus white wine and spirits promoted the gout risk at any dose. CONCLUSION: Our study suggested a J-shaped dose-response relationship of drinking with gout risk in females rather than males. For specific alcoholic beverages, light consumption of red wine and fortified wine was associated with reduced gout risk. These findings offer new insights into the roles of alcoholic beverages in gout, while further validation is warranted.

17.
BMC Med Imaging ; 24(1): 108, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38745134

RESUMO

BACKGROUND: The purpose of this research is to study the sonographic and clinicopathologic characteristics that associate with axillary lymph node metastasis (ALNM) for pure mucinous carcinoma of breast (PMBC). METHODS: A total of 176 patients diagnosed as PMBC after surgery were included. According to the status of axillary lymph nodes, all patients were classified into ALNM group (n = 15) and non-ALNM group (n = 161). The clinical factors (patient age, tumor size, location), molecular biomarkers (ER, PR, HER2 and Ki-67) and sonographic features (shape, orientation, margin, echo pattern, posterior acoustic pattern and vascularity) between two groups were analyzed to unclose the clinicopathologic and ultrasonographic characteristics in PMBC with ALNM. RESULTS: The incidence of axillary lymph node metastasis was 8.5% in this study. Tumors located in the outer side of the breast (upper outer quadrant and lower outer quadrant) were more likely to have lymphatic metastasis, and the difference between the two group was significantly (86.7% vs. 60.3%, P = 0.043). ALNM not associated with age (P = 0.437). Although tumor size not associated with ALNM(P = 0.418), the tumor size in ALNM group (32.3 ± 32.7 mm) was bigger than non-ALNM group (25.2 ± 12.8 mm). All the tumors expressed progesterone receptor (PR) positively, and 90% of all expressed estrogen receptor (ER) positively, human epidermal growth factor receptor 2 (HER2) were positive in two cases of non-ALNM group. Ki-67 high expression was observed in 36 tumors in our study (20.5%), and it was higher in ALNM group than non-ALNM group (33.3% vs. 19.3%), but the difference wasn't significantly (P = 0.338). CONCLUSIONS: Tumor location is a significant factor for ALNM in PMBC. Outer side location is more easily for ALNM. With the bigger size and/or Ki-67 higher expression status, the lymphatic metastasis seems more likely to present.


Assuntos
Adenocarcinoma Mucinoso , Axila , Neoplasias da Mama , Linfonodos , Metástase Linfática , Humanos , Feminino , Metástase Linfática/diagnóstico por imagem , Metástase Linfática/patologia , Pessoa de Meia-Idade , Neoplasias da Mama/patologia , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/metabolismo , Adulto , Idoso , Adenocarcinoma Mucinoso/diagnóstico por imagem , Adenocarcinoma Mucinoso/patologia , Adenocarcinoma Mucinoso/metabolismo , Adenocarcinoma Mucinoso/secundário , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Ultrassonografia/métodos , Biomarcadores Tumorais/metabolismo
18.
Sci Rep ; 14(1): 10934, 2024 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-38740841

RESUMO

Cyanobacteria bloom and the secondary metabolites released by the microorganism are extremely harmful to aquatic animals, yet study on their adverse effects in zoobenthos is rare. Corbicula fluminea widely distributed in freshwater environment with algal blooms. It is a typical filter feeding zoobenthos that may be affected by the secondary metabolites of cyanobacteria due to its high filtering rate. In this study, C. fluminea was exposed to Microcystis aeruginosa exudates (MaE) for 96 h, which was obtained from 5 × 105 cells/mL and 2.5 × 106 cells/mL exponential stage M. aeruginosa culture solution that represented cyanobacteria cell density needs environmental risk precaution control and emergent control, respectively. The responses of C. fluminea critical organs to MaE were analyzed and evaluated based on histopathological sections, antitoxicity biomarkers, and organ function biomarkers. The results showed that all the organs underwent structural disorders, cell vacuolization, apoptosis, and necrosis, and the damage levels increased as MaE concentration increased. The detoxification and antioxidant defense systems biomarkers in each organ response to MaE exposure differently and the level of reaction improved when MaE concentration increased. The siphon rate and acetylcholinesterase activity showed that the filtration function decreased significantly as the MaE concentration increased. Increased activity of glutathione S-transferase and amylase in the digestive gland indicate that it is the major detoxification organ of C. fluminea. Increased vitellogenin concentration and enlarged oocytes in the gonad indicate that MaE may have an estrogenic effect on C. fluminea. This study demonstrates that cyanobacteria threat benthic bivalves by inducing oxidative stress, inhibiting filtering feeding system, and disturbing digestion system and reproduction potential of C. fluminea.


Assuntos
Corbicula , Microcystis , Reprodução , Animais , Microcystis/metabolismo , Corbicula/metabolismo , Corbicula/microbiologia , Filtração , Biomarcadores/metabolismo
19.
Front Immunol ; 15: 1382449, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38745657

RESUMO

Background: Acute Respiratory Distress Syndrome (ARDS) or its earlier stage Acute lung injury (ALI), is a worldwide health concern that jeopardizes human well-being. Currently, the treatment strategies to mitigate the incidence and mortality of ARDS are severely restricted. This limitation can be attributed, at least in part, to the substantial variations in immunity observed in individuals with this syndrome. Methods: Bulk and single cell RNA sequencing from ALI mice and single cell RNA sequencing from ARDS patients were analyzed. We utilized the Seurat program package in R and cellmarker 2.0 to cluster and annotate the data. The differential, enrichment, protein interaction, and cell-cell communication analysis were conducted. Results: The mice with ALI caused by pulmonary and extrapulmonary factors demonstrated differential expression including Clec4e, Retnlg, S100a9, Coro1a, and Lars2. We have determined that inflammatory factors have a greater significance in extrapulmonary ALI, while multiple pathways collaborate in the development of pulmonary ALI. Clustering analysis revealed significant heterogeneity in the relative abundance of immune cells in different ALI models. The autocrine action of neutrophils plays a crucial role in pulmonary ALI. Additionally, there was a significant increase in signaling intensity between B cells and M1 macrophages, NKT cells and M1 macrophages in extrapulmonary ALI. The CXCL, CSF3 and MIF, TGFß signaling pathways play a vital role in pulmonary and extrapulmonary ALI, respectively. Moreover, the analysis of human single-cell revealed DCs signaling to monocytes and neutrophils in COVID-19-associated ARDS is stronger compared to sepsis-related ARDS. In sepsis-related ARDS, CD8+ T and Th cells exhibit more prominent signaling to B-cell nucleated DCs. Meanwhile, both MIF and CXCL signaling pathways are specific to sepsis-related ARDS. Conclusion: This study has identified specific gene signatures and signaling pathways in animal models and human samples that facilitate the interaction between immune cells, which could be targeted therapeutically in ARDS patients of various etiologies.


Assuntos
Lesão Pulmonar Aguda , Comunicação Celular , Perfilação da Expressão Gênica , Animais , Lesão Pulmonar Aguda/genética , Lesão Pulmonar Aguda/imunologia , Camundongos , Humanos , Comunicação Celular/imunologia , Transcriptoma , Síndrome do Desconforto Respiratório/imunologia , Síndrome do Desconforto Respiratório/genética , Modelos Animais de Doenças , Análise de Célula Única , Camundongos Endogâmicos C57BL , Neutrófilos/imunologia , Neutrófilos/metabolismo , COVID-19/imunologia , COVID-19/genética , Transdução de Sinais , Masculino , Macrófagos/imunologia , Macrófagos/metabolismo
20.
Exp Neurol ; 377: 114803, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38679281

RESUMO

Disruption of corticospinal tracts (CST) is a leading factor for motor impairments following intracerebral hemorrhage (ICH) in the striatum. Previous studies have shown that therapeutic hypothermia (HT) improves outcomes of ICH patients. However, whether HT has a direct protection effect on the CST integrity and the underlying mechanisms remain largely unknown. In this study, we employed a chemogenetics approach to selectively activate bilateral warm-sensitive neurons in the preoptic areas to induce a hypothermia-like state. We then assessed effects of HT treatment on the integrity of CST and motor functional recovery after ICH. Our results showed that HT treatment significantly alleviated axonal degeneration around the hematoma and the CST axons at remote midbrain region, ultimately promoted skilled motor function recovery. Anterograde and retrograde tracing revealed that HT treatment protected the integrity of the CST over an extended period. Mechanistically, HT treatment prevented mitochondrial swelling in degenerated axons around the hematoma, alleviated mitochondrial impairment by reducing mitochondrial ROS accumulation and improving mitochondrial membrane potential in primarily cultured cortical neurons with oxyhemoglobin treatment. Serving as a proof of principle, our study provided novel insights into the application of HT to improve functional recovery after ICH.


Assuntos
Hemorragia Cerebral , Hipotermia Induzida , Mitocôndrias , Tratos Piramidais , Animais , Tratos Piramidais/patologia , Hemorragia Cerebral/patologia , Hemorragia Cerebral/complicações , Hemorragia Cerebral/metabolismo , Camundongos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Masculino , Hipotermia Induzida/métodos , Camundongos Endogâmicos C57BL , Recuperação de Função Fisiológica/fisiologia , Células Cultivadas
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