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1.
BMC Musculoskelet Disord ; 25(1): 454, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38851696

RESUMO

BACKGROUND: Ulnar impingement syndrome is a prevalent source of ulnar carpal pain; however, there is ongoing debate regarding the specific location of shortening, the method of osteotomy, the extent of shortening, and the resulting biomechanical alterations. METHOD: To investigate the biomechanical changes in the distal radioulnar joint (DRUJ) resulting from different osteotomy methods, a cadaveric specimen was dissected, and the presence of a stable DRUJ structure was confirmed. Subsequently, three-dimensional data of the specimen were obtained using a CT scan, and finite element analysis was conducted after additional processing. RESULTS: The DRUJ stress did not change significantly at the metaphyseal osteotomy of 2-3 mm but increased significantly when the osteotomy length reached 5 mm. When the osteotomy was performed at the diaphysis, the DRUJ stress increased with the osteotomy length, and the increase was greater than that of metaphyseal osteotomy. Stress on the DRUJ significantly increases when the position is changed to pronation dorsi-extension. Similarly, the increase in stress in diaphyseal osteotomy was greater than that in metaphyseal osteotomy. When the model was subjected to a longitudinal load of 100 N, neither osteotomy showed a significant change in DRUJ stress at the neutral position. However, the 100 N load significantly increased stress on the DRUJ when the position was changed to pronation dorsi-extension, and the diaphyseal osteotomy significantly increased stress on the DRUJ. CONCLUSIONS: For patients with distal oblique bundle, metaphyseal osteotomy result in a lower increase in intra-articular pressure in the DRUJ compared to diaphyseal osteotomy. However, it is crucial to note that regardless of the specific type of osteotomy employed, it is advisable to avoid a shortening length exceeding 5 mm.


Assuntos
Cadáver , Análise de Elementos Finitos , Osteotomia , Ulna , Articulação do Punho , Humanos , Osteotomia/métodos , Osteotomia/efeitos adversos , Articulação do Punho/cirurgia , Articulação do Punho/diagnóstico por imagem , Articulação do Punho/fisiopatologia , Ulna/cirurgia , Ulna/diagnóstico por imagem , Fenômenos Biomecânicos/fisiologia , Estresse Mecânico , Suporte de Carga/fisiologia , Masculino
2.
Front Microbiol ; 15: 1374458, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38827153

RESUMO

Background: Tuberculous meningitis (TBM) is the most severe form of tuberculosis (TB) and can be difficult to diagnose and treat. We aimed to describe the clinical presentation, diagnosis, disease spectrum, outcome, and prognostic factors of patients treated for TBM in China. Methods: A multicenter retrospective study was conducted from 2009 to 2019 enrolling all presumptive TBM patients referred to Xijing tertiary Hospital from 27 referral centers in and around Shaanxi province, China. Patients with clinical features suggestive of TBM (abnormal CSF parameters) were included in the study if they had adequate baseline information to be classified as "confirmed," "probable," or "possible" TBM according to international consensus TBM criteria and remained in follow-up. Patients with a confirmed alternative diagnosis or severe immune compromise were excluded. Clinical presentation, central nervous system imaging, cerebrospinal fluid (CSF) results, TBM score, and outcome-assessed using the modified Barthel disability index-were recorded and compared. Findings: A total of 341 presumptive TBM patients met selection criteria; 63 confirmed TBM (25 culture positive, 42 Xpert-MTB/RIF positive), 66 probable TBM, 163 possible TBM, and 49 "not TBM." Death was associated with BMRC grade III (OR = 5.172; 95%CI: 2.298-11.641), TBM score ≥ 15 (OR = 3.843; 95%CI: 1.372-10.761), age > 60 years (OR = 3.566; 95%CI: 1.022-12.442), and CSF neutrophil ratio ≥ 25% (OR = 2.298; 95%CI: 1.027-5.139). Among those with confirmed TBM, nearly one-third (17/63, 27.0%) had a TBM score < 12; these patients exhibited less classic meningitis symptoms and signs and had better outcomes compared with those with a TBM score ≥ 12. In this group, signs of disseminated/miliary TB (OR = 12.427; 95%CI: 1.138-135.758) and a higher TBM score (≥15, OR = 8.437; 95%CI: 1.328-53.585) were most strongly associated with death. Conclusion: TBM patients who are older (>60 years) have higher TBM scores or CSF neutrophil ratios, have signs of disseminated/miliary TB, and are at greatest risk of death. In general, more effort needs to be done to improve early diagnosis and treatment outcome in TBM patients.

3.
NPJ Precis Oncol ; 8(1): 99, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38831114

RESUMO

Fetal adenocarcinoma of the lung (FLAC) is a rare form of lung adenocarcinoma and was divided into high-grade (H-FLAC) and low-grade (L-FLAC) subtypes. Despite the existence of some small case series studies, a comprehensive multi-omics study of FLAC has yet to be undertaken. In this study, we depicted the multi-omics landscapes of this rare lung cancer type by performing multi-regional sampling on 20 FLAC cases. A comparison of multi-omics profiles revealed significant differences between H-FLAC and L-FLAC in a multi-omic landscape. Two subtypes also showed distinct relationships between multi-layer intratumor heterogeneity (ITH). We discovered that a lower genetic ITH was significantly associated with worse recurrence-free survival and overall survival in FLAC patients, whereas higher methylation ITH in H-FLAC patients suggested a short survival. Our findings highlight the complex interplay between genetic and transcriptional heterogeneity in FLAC and suggest that different types of ITH may have distinct implications for patient prognosis.

4.
Front Microbiol ; 15: 1356365, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38835484

RESUMO

Objective: To examine the effects of an intervention with fructooligosaccharides (FOS), Saccharomyces boulardii, and their combination in a mouse model of colitis and to explore the mechanisms underlying these effects. Methods: The effects of FOS, S. boulardii, and their combination were evaluated in a DSS-induced mouse model of colitis. To this end, parameters such as body weight, the disease activity index (DAI), and colon length were examined in model mice. Subsequently, ELISA was employed to detect the serum levels of proinflammatory cytokines. Histopathological analysis was performed to estimate the progression of inflammation in the colon. Gas chromatography was used to determine the content of short-chain fatty acids (SCFAs) in the feces of model mice. Finally, 16S rRNA sequencing technology was used to analyze the gut microbiota composition. Results: FOS was slight effective in treating colitis and colitis-induced intestinal dysbiosis in mice. Meanwhile, S. boulardii could significantly reduced the DAI, inhibited the production of IL-1ß, and prevented colon shortening. Nevertheless, S. boulardii treatment alone failed to effectively regulate the gut microbiota. In contrast, the combined administration of FOS/S. boulardii resulted in better anti-inflammatory effects and enabled microbiota regulation. The FOS/S. boulardii combination (109 CFU/ml and 107 CFU/ml) significantly reduced the DAI, inhibited colitis, lowered IL-1ß and TNF-α production, and significantly improved the levels of butyric acid and isobutyric acid. However, FOS/S. boulardii 109 CFU/ml exerted stronger anti-inflammatory effects, inhibited IL-6 production and attenuated colon shortening. Meanwhile, FOS/S. boulardii 107 CFU/ml improved microbial regulation and alleviated the colitis-induced decrease in microbial diversity. The combination of FOS and S. boulardii significantly increased the abundance of Parabacteroides and decreased the abundance of Escherichia-Shigella. Additionally, it promoted the production of acetic acid and propionic acid. Conclusion: Compared with single administration, the combination can significantly increase the abundance of beneficial bacteria such as lactobacilli and Bifidobacteria and effectively regulate the gut microbiota composition. These results provide a scientific rationale for the prevention and treatment of colitis using a FOS/S. boulardii combination. They also offer a theoretical basis for the development of nutraceutical preparations containing FOS and S. boulardii.

5.
Food Sci Nutr ; 12(6): 3893-3909, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38873488

RESUMO

In clinical flap practice, there are a lot of studies being done on how to promote the survival of distal random flap necrosis in the hypoxic and ischemic state. As a traditional Chinese medicine, dihydromyricetin (DHM) is crucial in preventing oxidative stress and apoptosis in a number of disorders. In this work, we examined the impact of DHM on the ability to survive of ischemia flaps and looked into its fundamental mechanism. Our results showed that DHM significantly increased the ischemic flaps' survival area, encouraged angiogenesis and blood flow, reduced oxidative stress and apoptosis, and stimulated KEAP1-Nrf2 (Kelch-like ECH-associated protein 1-nuclear factor erythroid 2-related factor) signaling pathways. Adeno-associated virus (AAV) upregulation of KEAP1 expression also negated the favorable effects of DHM on flap survival. By activating KEAP1-Nrf2 signaling pathways, DHM therapy promotes angiogenesis while reducing oxidative stress and apoptosis.

6.
Mol Med Rep ; 30(2)2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38904199

RESUMO

Septic acute kidney injury (AKI) is considered as a severe and frequent complication that occurs during sepsis. Mounting evidence has confirmed the pivotal pathogenetic roles of microRNA (miRNA or miR) in sepsis­induced AKI; however, the role of miRNAs and their underlying mechanisms in sepsis­induced AKI have not been entirely understood. The present study aimed to elucidate the functions of special miRNAs during sepsis­induced AKI and its underlying mechanism. First, a number of differently expressed miRNAs was identified based on the microarray dataset GSE172044. Subsequently, lipopolysaccharide (LPS) was used to induce AKI in mice, and the role of miR­17­5p on AKI was clarified. Finally, the related molecular mechanisms were further examined by western blotting and immunohistochemical analysis. MiR­17­5p was found to be continuously decreased and reached the bottom at h 24 after AKI in mice. Functionally, injection of agomiR­17­5p could observably improve renal injury and survival rate, as well as inhibit inflammatory cytokine production and renal cell apoptosis in mice after AKI. On the contrary, injection of antagomiR­17­5p aggravated LPS­induced renal injury, inflammation and apoptosis in mice after AKI. Moreover, transforming growth factor ß receptor 2 (TGFßR2) was identified as a direct target of miR­17­5p, and its downstream phosphorylated Smad3 was also suppressed by miR­17­5p upregulation. Taken together, these results demonstrated that miR­17­5p overexpression may exhibit a beneficial effect by attenuating LPS­induced inflammation and apoptosis via regulating the TGFßR2/TGF­ß/Smad3 signaling pathway, indicating that miR­17­5p could act as a potential target for sepsis treatment.


Assuntos
Injúria Renal Aguda , Apoptose , Inflamação , MicroRNAs , Receptor do Fator de Crescimento Transformador beta Tipo II , Sepse , Animais , MicroRNAs/genética , MicroRNAs/metabolismo , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/genética , Sepse/complicações , Sepse/metabolismo , Sepse/genética , Apoptose/genética , Camundongos , Inflamação/genética , Inflamação/metabolismo , Masculino , Receptor do Fator de Crescimento Transformador beta Tipo II/genética , Receptor do Fator de Crescimento Transformador beta Tipo II/metabolismo , Lipopolissacarídeos , Modelos Animais de Doenças , Transdução de Sinais , Proteína Smad3/metabolismo , Proteína Smad3/genética , Camundongos Endogâmicos C57BL , Citocinas/metabolismo
7.
J Org Chem ; 89(12): 9056-9062, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38857440

RESUMO

A palladium(II)-catalyzed Markovnikov hydroboration of aryl alkenes with readily available bis(pinacolato)diboron (B2pin2) is reported. The reaction proceeded with low catalyst loading (0.5 mol %) in the absence of N- or P-containing ligands, affording the products in up to 90% yield. Trifluoracetic acid serves as the hydrogen source, enabling the synthesis of benzylic boronic esters under mild ambient conditions.

8.
Front Chem ; 12: 1398946, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38800577

RESUMO

Amino acid-derived quaternary ammonium salts were successfully applied in the asymmetric aza-Henry reaction of nitromethane to N-Boc trifluoromethyl ketimines. α-Trifluoromethyl ß-nitroamines were synthesized in good to excellent yields with moderate to good enantioselectivities. This reaction is distinguished by its mild conditions, low catalyst loading (1 mol%), and catalytic base. It also proceeded on a gram scale without loss of enantioselectivity. The products were transformed to a series of adamantane-type compounds containing chiral trifluoromethylamine fragments. The potent anticancer activities of these compounds against liver cancer HepG2 and melanoma B16F10 were evaluated. Six promising compounds with notable efficacy have potential for further development.

9.
Theranostics ; 14(7): 2897-2914, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38773985

RESUMO

Background: IL-35 potently inhibits immune responses both in vivo and in vitro. However, the specific characteristics of IL-35-producing cells, including their developmental origin, cellular phenotype, and function, are unknown. Methods: By using a novel IL-35 reporter mouse (Ebi3-Dre-Thy1.1) and double transgenic fate-mapping reporter mice (35EbiT-Rosa26-rox-tdTomato reporter mice or Foxp3 fate-mapping system), we tracked and analyzed the differentiation and developmental trajectories of Tr35 cells in vivo. And then we investigated the therapeutic effects of OVA-specific Tr35 cells in an OVA-induced allergic airway disease model. Results: We identified a subset of cells, denoted Tr35 cells, that secrete IL-35 but do not express Foxp3. These cells have high expression of molecules associated with T-cell activation and can inhibit T-cell proliferation in vitro. Our analyses showed that Tr35 cells are a distinct subpopulation of cells that are independent of Tr1 cells. Tr35 cells exhibit a unique gene expression profile and tissue distribution. The presence of Thy1.1 (Ebi3) expression in Tr35 cells indicates their active secretion of IL-35. However, the proportion of ex-Tr35 cells (Thy1.1-) is significantly higher compared to Tr35 cells (Thy1.1+). This suggests that Tr35 cells possess the ability to regulate IL-35 expression rapidly in vivo. Tr35 cells downregulated the expression of the inflammatory cytokines IL-4, IFN-γ and IL-17A. However, once Tr35 cells lost IL-35 expression and became exTr35 cells, the expression of inflammatory cytokines was upregulated. Importantly, our findings indicate that Tr35 cells have therapeutic potential. In an OVA-induced allergic airway disease mouse model, Tr35 cell reinfusion significantly reduced airway hyperresponsiveness and histopathological airway and lung inflammation. Conclusions: We have identified a subset of Tregs, Tr35 cells, that are distinct from Tr1 cells. Tr35 cells can dynamically regulate the secretion of inflammatory cytokines by controlling IL-35 expression to regulate inflammatory immune responses.


Assuntos
Interleucinas , Camundongos Transgênicos , Linfócitos T Reguladores , Animais , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Interleucinas/metabolismo , Interleucinas/genética , Camundongos , Fatores de Transcrição Forkhead/metabolismo , Fatores de Transcrição Forkhead/genética , Modelos Animais de Doenças , Plasticidade Celular , Camundongos Endogâmicos C57BL , Ativação Linfocitária , Ovalbumina/imunologia , Proliferação de Células , Diferenciação Celular , Feminino
10.
Int J Biol Macromol ; 270(Pt 2): 132471, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38763235

RESUMO

Enantioselective antibodies have emerged as great potential biomaterials in the fields of immunoassays and chiral separation. However, cross-reactivity of antibodies to the distomer may severely restrict the application. Comprehending the interaction mechanism between antibodies and enantiomers could be beneficial to produce superior enantioselective antibodies. In this study, a pair of recombinant antibodies (RAbs) against metolachlor enantiomers at chiral carbon (αSS-MET and αSR-MET) were generated and characterized. The αSS-MET-RAb and αSR-MET-RAb showed comparable sensitivity and specificity to the parental monoclonal antibodies by icELISA, with IC50 values of 3.45 and 223.77 ng/mL, respectively. Moreover, the complex structures of RAbs and corresponding eutomer were constructed and analyzed, and site-specific mutagenesis was utilized to verify the reliability of the enantioselective mechanism elucidated. It demonstrated that the strength of the interaction between the chiral center region of eutomer and the antibody was the key factor for the enantioselectivity of antibody. Increasing this interaction could limit the conformational adjustment of the distomer in a specific chiral recognition cavity, thus decreasing the affinity of the antibody to the distomer. This work provided the in-depth analysis of enantioselective mechanism for two RAbs and paved the way to regulate antibody enantioselective performance for immunoassays of chiral compounds.


Assuntos
Acetamidas , Herbicidas , Estereoisomerismo , Herbicidas/química , Acetamidas/química , Anticorpos Monoclonais/química , Animais , Proteínas Recombinantes/química
12.
Nat Commun ; 15(1): 4559, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38811653

RESUMO

Extreme within-lake conditions have the potential to exert detrimental effects on lakes. Here we use satellite observations to investigate how the occurrence of multiple types of extremes, notably algal blooms, lake heatwaves, and low lake levels, have varied in 2724 lakes since the 1980s. Our study, which focuses on bloom-affected lakes, suggests that 75% of studied lakes have experienced a concurrent increase in at least two of the extremes considered (27% defined as having a notable increase), with 25% experiencing an increase in frequency of all three extremes (5% had a notable increase). The greatest increases in the frequency of these extremes were found in regions that have experienced increases in agricultural fertilizer use, lake warming, and a decline in water availability. As extremes in lakes become more common, understanding their impacts must be a primary focus of future studies and they must be carefully considered in future risk assessments.

13.
J Chem Phys ; 160(18)2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38738613

RESUMO

Metal ion-induced water pollution is attracting increasing public attention. Perovskite quantum dots and metal-organic frameworks (MOFs), owing to their outstanding properties, hold promise as ideal probes for detecting metal ions. In this study, a composite material, MAPbBr3@PCN-221(Fe), was prepared by encapsulating MAPbBr3 quantum dots with PCN-221(Fe), demonstrating high chemical stability and good reusability. The composite material shows a sensitive fluorescence turn-on signal in the presence of silver ions. The fluorescence intensity of the composite material exhibits a linear relationship with the concentration of Ag+ in the solution, with a low detection limit of 8.68 µM. Moreover, the fluorescence signal exhibits a strong selectivity for Ag+, enabling the detection of Ag+ concentration. This fluorescence turn-on signal originates from the Ag+-bridged energy transfer from the conductive band of MAPbBr3 to the excited state of the MOF, which is directly proportional to the concentration of silver ions. Simultaneously, this finding may open up a new possibility in artificial controlled energy transfer from perovskite to MOF for future development.

14.
Biochim Biophys Acta Mol Basis Dis ; 1870(6): 167234, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38750769

RESUMO

The 5-year survival for non-small cell lung cancer (NSCLC) remains <20 %, primarily due to the early symptoms of lung cancer are inconspicuous. Prompt identification and medical intervention could serve as effective strategies for mitigating the death rate. We therefore set out to identify biomarkers to help diagnose NSCLC. CircRNA microarray and qRT-PCR reveal that sputum circ_0006949 is a potential biomarker for the early diagnosis and therapy of NSCLC, which can enhance the proliferation and clone formation, regulate the cell cycle, and accelerate the migration and invasion of NSCLC cells. Circ_0006949 and miR-4673 are predominantly co-localized in the cytoplasm of NSCLC cell lines and tissues; it upregulates GLUL by adsorption of miR-4673 through competing endogenous RNAs mechanism. The circ_0006949/miR-4673/GLUL axis exerts pro-cancer effects in vitro and in vivo. Circ_0006949 can boost GLUL catalytic activity, and they are highly expressed in NSCLC tissues and correlate with poor prognosis. In summary, circ_0006949 is a potential biomarker for the early diagnosis and therapy of NSCLC. This novel sputum circRNA is statistically more predictive than conventional serum markers for NSCLC diagnosis. Non-invasive detection of patients with early-stage NSCLC using sputum has shown good potential for routine diagnosis and possible screening.


Assuntos
Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares , MicroRNAs , RNA Circular , Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Animais , Linhagem Celular Tumoral , Camundongos , Masculino , Feminino , Movimento Celular/genética , Camundongos Nus , Escarro/metabolismo
15.
Biochem Pharmacol ; 225: 116251, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38701867

RESUMO

Hepatocellular carcinoma (HCC) is the main histological subtype of primary liver cancer and remains one of the most common solid malignancies globally. Ferroptosis was recently defined as an iron-catalyzed form of regulated necrosis. Because cancer cells exhibit higher iron requirements than noncancer cells, treatment with ferroptosis-inducing compounds may be a feasible strategy for cancer therapy. However, cancer cells develop acquired resistance to evade ferroptosis, and the mechanisms responsible for ferroptosis resistance are not fully clarified. In the current study, we reported that DDX39B was downregulated during sorafenib-induced ferroptosis in a dose- and time-dependent manner. Exogenous introduction of DDX39B ensured the survival of HCC cells upon exposure to sorafenib, while the opposite phenomenon was observed in DDX39B-silenced HCC cells. Mechanistically, we demonstrated that DDX39B increased GPX4 levels by promoting the splicing and cytoplasmic translocation of GPX4 pre-mRNA, which was sufficient to detoxify sorafenib-triggered excess lipid ROS production, lipid peroxidation accumulation, ferrous iron levels, and mitochondrial damage. Inhibition of DDX39B ATPase activity by CCT018159 repressed the splicing and cytoplasmic export of GPX4 pre-mRNA and synergistically assisted sorafenib-induced ferroptotic cell death in HCC cells. Taken together, our data uncover a novel role for DDX39B in ferroptosis resistance by modulating the maturation of GPX4 mRNA via a posttranscriptional approach and suggest that DDX39B inhibition may be a promising therapeutic strategy to enhance the sensitivity and vulnerability of HCC cells to sorafenib.


Assuntos
Antineoplásicos , Carcinoma Hepatocelular , RNA Helicases DEAD-box , Ferroptose , Neoplasias Hepáticas , Fosfolipídeo Hidroperóxido Glutationa Peroxidase , Precursores de RNA , Sorafenibe , Ferroptose/efeitos dos fármacos , Ferroptose/fisiologia , Sorafenibe/farmacologia , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/genética , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , RNA Helicases DEAD-box/metabolismo , RNA Helicases DEAD-box/genética , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/genética , Precursores de RNA/metabolismo , Precursores de RNA/genética , Antineoplásicos/farmacologia , Animais , Camundongos , Splicing de RNA/efeitos dos fármacos , Camundongos Nus , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Camundongos Endogâmicos BALB C , Masculino , Citoplasma/metabolismo , Citoplasma/efeitos dos fármacos
16.
J Hazard Mater ; 471: 134428, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38691928

RESUMO

Individual application of sulfide modification and electromagnetic field (EMF) can enhance the reactivity of nanoscale zero-valent iron (nZVI), yet the potential of both in combination is not clear. This work found that the reactivity of nZVI towards decabromodiphenyl ether was significantly enhanced by the combined effect of sulfidation and EMF. The specific reaction rate constant of nZVI increased by 7 to 10 times. A series of characterization results revealed that the sulfidation level not only affects the inherent reactivity but also the magnetic-induced heating (MIH) and corrosion (MIC) of nZVI. These collectively influence the degradation efficiency of nZVI under EMF. Sulfidation generally diminished the MIH effect. The low degree of sulfidation (S/Fe = 0.1) slightly reduced the MIC effect by 21.4%. However, the high degree of sulfidation (S/Fe = 0.4) led to significantly enhanced MIC effect by 107.1%. For S/Fe = 0.1 and 0.4, the overall enhancement in the reactivity resulting from EMF was alternately dominated by the contributions of MIH and MIC. This work provides valuable insights into the MIH and MIC effects about the sulfidation level of nZVI, which is needed for further exploration and optimization of this combined technology.

17.
Cell Biol Int ; 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38706122

RESUMO

Cisplatin is commonly used for the chemotherapy of tongue squamous cell carcinoma (TSCC); however, adverse side effects and drug resistance impact its therapeutic efficacy. Capsaicin is an active ingredient in chili peppers that exerts antitumor effects, whether it exerts antitumor effects on cisplatin-resistant cells remains unknown. Therefore, in this study, we investigated the effect of capsaicin on cisplatin resistance in TSCC cells and explored the underlying mechanisms. A cisplatin-resistant TSCC cell line was established by treated with increasing cisplatin concentrations. Combined treatment with cisplatin and capsaicin decreased the glucose consumption and lactate dehydrogenase activity and increased the adenosine triphosphate production both in vitro and in vivo, suggesting the inhibition of the Warburg effect. Moreover, this combined treatment induced cell apoptosis and significantly upregulated the levels of proapoptotic proteins, such as Bax, cleaved caspase-3, -7, and -9, and apoptosis-inducing factor. In contrast, levels of the antiapoptotic protein, Bcl-2, were downregulated. Additionally, LKB1 and AMPK activities were stimulated, whereas those of AKT and mTOR were suppressed. Notably, AMPK knockdown abolished the inhibitory effects of capsaicin and cisplatin on the AKT/mTOR signaling pathway and Warburg effect. Overall, combined treatment with capsaicin and cisplatin reversed cisplatin resistance by inhibiting the Warburg effect and facilitating mitochondrial-dependent apoptosis via the AMPK/AKT/mTOR axis. Our findings suggest combination therapy with capsaicin and cisplatin as a potentially novel strategy and highlight capsaicin as a promising adjuvant drug for TSCC treatment.

18.
Hum Reprod ; 39(6): 1275-1290, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38592717

RESUMO

STUDY QUESTION: Can the addition of late embryogenesis-abundant (LEA) proteins as a cryoprotective agent during the vitrification cryopreservation of in vitro matured oocytes enhance their developmental potential after fertilization? SUMMARY ANSWER: LEA proteins improve the developmental potential of human in vitro matured oocytes following cryopreservation, mostly by downregulating FOS genes, reducing oxidative stress, and inhibiting the formation of ice crystals. WHAT IS KNOWN ALREADY: Various factors in the vitrification process, including cryoprotectant toxicity, osmotic stress, and ice crystal formation during rewarming, can cause fatal damage to oocytes, thereby affecting the oocytes developmental potential and subsequent clinical outcomes. Recent studies have shown that LEA proteins possess high hydrophilicity and inherent stress tolerance, and can reduce low-temperature damage, although the molecular mechanism it exerts protective effects is still unclear. STUDY DESIGN, SIZE, DURATION: Two LEA proteins extracted and purified by us were added to solutions for vitrification-warming of oocytes at concentrations of 10, 100, and 200 µg/mL, to determine the optimal protective concentration for each protein. Individual oocyte samples were collected for transcriptomic analysis, with each group consisting of three sample replicates. PARTICIPANTS/MATERIALS, SETTING, METHODS: Immature oocytes were collected from patients who were undergoing combined in vitro fertilization (IVF) treatment and who had met the designated inclusion and exclusion criteria. These oocytes underwent in vitro maturation (IVM) culture for experimental research. A fluorescence microscope was used to detect the levels of mitochondrial membrane potential (MMP), reactive oxygen species (ROS), and calcium in the mitochondria of vitrified-warmed human oocytes treated with different concentrations of LEA proteins, and the protective effect of the protein on mitochondrial function was assessed. The levels of intracellular ice recrystallization inhibition (IRI) in human oocytes after vitrification-warming were characterized by the cryomicroscope, to determine the LEA proteins inhibitory effect on recrystallization. By analyzing transcriptome sequencing data to investigate the potential mechanism through which LEA proteins exert their cryoprotective effects. MAIN RESULTS AND THE ROLE OF CHANCE: The secondary structures of AfrLEA2 and AfrLEA3m proteins were shown to consist of a large number of α-helices and the proteins were shown to be highly hydrophilic, in agreement with previous reports. Confocal microscopy results showed that the immunofluorescence of AfrLEA2-FITC and AfrLEA3m-FITC-labeled proteins appeared to be extracellular and did not penetrate the cell membrane compared with the fluorescein isothiocyanate (FITC) control group, indicating that both AfrLEA2 and AfrLEA3m proteins were extracellular. The group treated with 100 µg/mL AfrLEA2 or AfrLEA3m protein had more uniform cytoplasmic particles and fewer vacuoles compared to the 10 and 200 µg/mL groups and were closest to the fresh group. In the 100 µg/mL groups, MMPs were significantly higher while ROS and calcium levels were significantly lower than those in the control group and were closer to the levels observed in fresh oocytes. Meanwhile, 100 µg/mL of AfrLEA2 or AfrLEA3m protein caused smaller ice crystal formation in the IRI assay compared to the control group treated with dimethylsulphoxide (DMSO) and ethylene glycol (EG); thus, the recrystallization inhibition was superior to that with the conventional cryoprotectants DMSO and EG. Further results revealed that the proteins improved the developmental potential of human oocytes following cryopreservation, likely by downregulating FOS genes and reducing oxidative stress. LIMITATIONS, REASONS FOR CAUTION: The in vitro-matured metaphase II (IVM-MII) oocytes used in the study, due to ethical constraints, may not accurately reflect the condition of MII oocytes in general. The AfrLEA2 and AfrLEA3m proteins are recombinant proteins and their synthetic stability needs to be further explored. WIDER IMPLICATIONS OF THE FINDINGS: LEA proteins, as a non-toxic and effective cryoprotectant, can reduce the cryoinjury of oocytes during cryopreservation. It provides a new promising method for cryopreservation of various cell types. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the National Key Research and Development Program of China (2022YFC2703000) and the National Natural Science Foundation of China (52206064). The authors declare no competing interest. TRIAL REGISTRATION NUMBER: N/A.


Assuntos
Criopreservação , Técnicas de Maturação in Vitro de Oócitos , Oócitos , Vitrificação , Humanos , Oócitos/efeitos dos fármacos , Oócitos/metabolismo , Técnicas de Maturação in Vitro de Oócitos/métodos , Feminino , Criopreservação/métodos , Crioprotetores/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Fertilização in vitro/métodos
19.
Cancer Lett ; 591: 216860, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38583650

RESUMO

Cancer is the result of genetic abnormalities that cause normal cells to grow into neoplastic cells. Cancer is characterized by several distinct features, such as uncontrolled cell growth, extensive spreading to other parts of the body, and the ability to resist treatment. The scientists have stressed the development of nanostructures as novel therapeutic options in suppressing cancer, in response to the emergence of resistance to standard medicines. One of the specific mechanisms with dysregulation during cancer is autophagy. Nanomaterials have the ability to specifically carry medications and genes, and they can also enhance the responsiveness of tumor cells to standard therapy while promoting drug sensitivity. The primary mechanism in this process relies on autophagosomes and their fusion with lysosomes to break down the components of the cytoplasm. While autophagy was initially described as a form of cellular demise, it has been demonstrated to play a crucial role in controlling metastasis, proliferation, and treatment resistance in human malignancies. The pharmacokinetic profile of autophagy modulators is poor, despite their development for use in cancer therapy. Consequently, nanoparticles have been developed for the purpose of delivering medications and autophagy modulators selectively and specifically to the cancer process. Furthermore, several categories of nanoparticles have demonstrated the ability to regulate autophagy, which plays a crucial role in defining the biological characteristics and response to therapy of tumor cells.


Assuntos
Autofagia , Nanoestruturas , Neoplasias , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Neoplasias/genética , Neoplasias/metabolismo , Autofagia/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Nanopartículas , Resistencia a Medicamentos Antineoplásicos , Animais
20.
JACS Au ; 4(4): 1356-1364, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38665665

RESUMO

Steroidal pharmaceuticals with a 10α-methyl group or without the methyl group at C10-position are important medicines, but their synthesis is quite challenging, due to that the natural steroidal starting materials usually have a 10ß-methyl group which is difficult to be inverted to 10α-methyl group. In this study, 3-((1R,3aS,4S,7aR)-1-((S)-1-hydroxypropan-2-yl)-7a-methyl-5-oxooctahydro-1H-inden-4-yl) propanoic acid (HIP-IPA, 2e) was demonstrated as a valuable intermediate for the synthesis of this kind of active pharmaceutical ingredients (APIs) with a side chain at C17-position. Knockout of a ß-hydroxyacyl-CoA dehydrogenase gene and introduction of a sterol aldolase gene into the genetically modified strains of Mycobacterium fortuitum (ATCC 6841) resulted in strains N13Δhsd4AΩthl and N33Δhsd4AΩthl, respectively. Both strains transformed phytosterols into 2e. Compound 2e was produced in 62% isolated yield (25 g) using strain N13Δhsd4AΩthl, and further converted to (3S,3aS,9aS,9bS)-3-acetyl-3a,6-dimethyl-1,2,3,3a,4,5,8,9,9a,9b-decahydro-7H-cyclopenta[a]naphthalen-7-one, which is the key intermediate for the synthesis of dydrogesterone. This study not only overcomes a challenging synthetic problem by enabling an efficient synthesis of dydrogesterone-like steroidal APIs from phytosterols, the well-recognized cheap and readily available biobased raw materials, but also provides insights for redesigning the metabolic pathway of phytosterols to produce other new compounds of relevance to the steroidal pharmaceutical industry.

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