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1.
Carbohydr Polym ; 335: 122078, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38616098

RESUMO

Microbial polysaccharides (MPs) are biopolymers secreted by microorganisms such as bacteria and fungi during their metabolic processes. Compared to polysaccharides derived from plants and animals, MPs have advantages such as wide sources, high production efficiency, and less susceptibility to natural environmental influences. The most attractive feature of MPs lies in their diverse biological activities, such as antioxidative, anti-tumor, antibacterial, and immunomodulatory activities, which have demonstrated immense potential for applications in functional foods, cosmetics, and biomedicine. These bioactivities are precisely regulated by their sophisticated molecular structure. However, the mechanisms underlying this precise regulation are not yet fully understood and continue to evolve. This article presents a comprehensive review of the most representative species of MPs, including their fermentation and purification processes and their biomedical applications in recent years. In particular, this work presents an in-depth analysis into the structure-activity relationships of MPs across multiple molecular levels. Additionally, this review discusses the challenges and prospects of investigating the structure-activity relationships, providing valuable insights into the broad and high-value utilization of MPs.


Assuntos
Antibacterianos , Antioxidantes , Animais , Antibacterianos/farmacologia , Antioxidantes/farmacologia , Transporte Biológico , Fermentação , Alimento Funcional
2.
Quant Imaging Med Surg ; 14(4): 3131-3145, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38617169

RESUMO

Background: The MYCN copy number category is closely related to the prognosis of neuroblastoma (NB). Therefore, this study aimed to assess the predictive ability of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) radiomic features for MYCN copy number in NB. Methods: A retrospective analysis was performed on 104 pediatric patients with NB that had been confirmed by pathology. To develop the Bio-omics model (B-model), which incorporated clinical and biological aspects, PET/CT radiographic features, PET quantitative parameters, and significant features with multivariable stepwise logistic regression were preserved. Important radiomics features were identified through least absolute shrinkage and selection operator (LASSO) and univariable analysis. On the basis of radiomics features obtained from PET and CT scans, the radiomics model (R-model) was developed. The significant bio-omics and radiomics features were combined to establish a Multi-omics model (M-model). The above 3 models were established to differentiate MYCN wild from MYCN gain and MYCN amplification (MNA). The calibration curve and receiver operating characteristic (ROC) curve analyses were performed to verify the prediction performance. Post hoc analysis was conducted to compare whether the constructed M-model can distinguish MYCN gain from MNA. Results: The M-model showed excellent predictive performance in differentiating MYCN wild from MYCN gain and MNA, which was better than that of the B-model and R-model [area under the curve (AUC) 0.83, 95% confidence interval (CI): 0.74-0.92 vs. 0.81, 95% CI: 0.72-0.90 and 0.79, 95% CI: 0.69-0.89]. The calibration curve showed that the M-model had the highest reliability. Post hoc analysis revealed the great potential of the M-model in differentiating MYCN gain from MNA (AUC 0.95, 95% CI: 0.89-1). Conclusions: The M-model model based on bio-omics and radiomics features is an effective tool to distinguish MYCN copy number category in pediatric patients with NB.

3.
ACS Omega ; 9(14): 16063-16070, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38617677

RESUMO

The efficient and clean utilization of urban waste can substitute for partial fossil fuels and reduce total carbon emissions. Fuel combustion is divided into three stages. Before the fire, the fuel is put into the furnace to reach the preparation stage of the fire temperature, the combustion stage takes place after the ignition temperature is reached, and finally, the combustion is completed. This article employs numerical simulation methods to comprehensively study the effects of various factors on the combustion characteristics of waste in a mechanical grate incinerator, including the inclination angle of the front arch, fuel properties, height of the front and rear arches, air distribution methods, and speed of the grate chain rotation. The results indicate that when the rear arch angle is set at 25°, the airflow distribution within the furnace is uniform and the high-temperature flue gas exhibits an ideal "L" shaped flow, achieving favorable characteristics of airflow distribution inside the furnace. With this structure, the airflow from the rear arch can adequately penetrate deep into the front arch area, thereby forming an efficient T-shaped combustion flame.

4.
Asian J Androl ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38624201

RESUMO

Knowledge about the effect of different prostate biopsy approaches on the prostate cancer detection rate (CDR) in patients with gray-zone prostate-specific antigen (PSA) is limited. We performed this study to compare the CDR among patients who underwent different biopsy approaches and had rising PSA levels in the gray zone. Two hundred and twenty-two patients who underwent transrectal prostate biopsy (TRB) and 216 patients who underwent transperineal prostate biopsy (TPB) between June 2016 and September 2022 were reviewed in this study. In addition, 110 patients who received additional targeted biopsies following the systematic TPB were identified. Clinical parameters, including age, PSA derivative, prostate volume (PV), and needle core count, were recorded. The data were fitted via propensity score matching (PSM), adjusting for potential confounders. TPB outperformed TRB in terms of the CDR (49.6% vs 28.3%, P = 0.001). The clinically significant prostate cancer (csPCa) detection rate was not significantly different between TPB and TRB (78.6% vs 68.8%, P = 0.306). In stratified analysis, TPB outperformed TRB in CDR when the age of patients was 65-75 years (59.0% vs 22.0%, P < 0.001), when PV was 25.00-50.00 ml (63.2% vs 28.3%, P < 0.001), and when needle core count was no more than 12 (58.5% vs 31.5%, P = 0.005). The CDR (P = 0.712) and detection rate of csPCa (P = 0.993) did not significantly differ among the systematic, targeted, and combined biopsies. TPB outperformed TRB in CDR for patients with gray-zone PSA. Moreover, performing target biopsy after systematic TPB provided no additional benefits in CDR.

5.
Food Sci Nutr ; 12(4): 2917-2931, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38628198

RESUMO

Sinapic acid (SA) is renowned for its many pharmacological activities as a polyphenolic compound. The cause of polycystic ovary syndrome (PCOS), a commonly encountered array of metabolic and hormonal abnormalities in females, has yet to be determined. The present experiment was performed to evaluate the antifibrotic properties of SA in rats with letrozole-induced PCOS-related ovarian fibrosis. SA treatment successfully mitigated the changes induced by letrozole in body weight (BW) (p < .01) and relative ovary weight (p < .05). Histological observation revealed that SA reduced the number of atretic and cystic follicles (AFs) and (CFs) (p < .01), as well as ovarian fibrosis, in PCOS rats. Additionally, SA treatment impacted the serum levels of sex hormones in PCOS rats. Luteinizing hormone (LH) and testosterone (T) levels were decreased (p < .01, p < .05), and follicle-stimulating hormone (FSH) levels were increased (p < .05). SA administration also decreased triglyceride (TG) (p < .01) and total cholesterol (TC) levels (p < .05) and increased high-density lipoprotein cholesterol (HDL-C) levels (p < .01), thereby alleviating letrozole-induced metabolic dysfunction in PCOS rats. Furthermore, SA treatment targeted insulin resistance (IR) and increased the messenger RNA (mRNA) levels of antioxidant enzymes in the ovaries of PCOS rats. Finally, SA treatment enhanced the activity of peroxisome proliferator-activated receptor-γ (PPAR-γ), reduced the activation of transforming growth factor-ß1 (TGF-ß1)/Smads, and decreased collagen I, α-smooth muscle actin (α-SMA), and connective tissue growth factor (CTGF) levels in the ovaries of PCOS rats. These observations suggest that SA significantly ameliorates metabolic dysfunction and oxidative stress and ultimately reduces ovarian fibrosis in rats with letrozole-induced PCOS.

6.
Food Sci Nutr ; 12(4): 2619-2633, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38628216

RESUMO

The present study aimed to prepare and evaluate a new probiotic functional beverage, using single-probiotic and compound probiotic fermentation on okara. Four different forms of fermentation microorganisms used were Lacticaseibacillus rhamnosus S24 (Lr), Lacticaseibacillus paracasei 6244 (Lp), Lactobacillus acidophilus 11,073 (La), and mixed fermentation (Lr + Lp + La). The physicochemical properties, antioxidant activity, flavor change, and storage period of fermented okara beverages with probiotics were investigated. The results showed that different fermentation schemes could significantly improve the physicochemical properties, antioxidant activity, and sensory quality of the okara beverages. The number of viable bacteria in the Lp group (3.53 × 108 CFU/mL), isoflavone content (0.514 µg/mL) were the highest; total phenol and flavonoid content were 3.32 and 5.68 times higher than in the CK group, respectively. DPPH and ABTS+ free radical scavenging rates were increased by 11.32% and 20%, respectively (p < .05). Through SPME/GC-MS analysis, 44 volatile compounds were identified in the Lr + Lp + La groups, mainly as a result of changes in alcohols and aldehydes produced by fermentation metabolism. It enhances the floral and fruity aroma of the okara beverage. All probiotic-fermented okara beverages can be stored at 4°C for 15 days, with probiotic activity greater than 107 CFU/mL. This study can obtain a probiotic okara beverage rich in soybean isoflavones and with good flavor. Overall, okara can be used to develop functional beverages containing probiotics and contribute to a zero-waste approach in the food industry.

7.
Acta Pharmacol Sin ; 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38632318

RESUMO

Frizzled receptors (FZDs) are key contributors intrinsic to the Wnt signaling pathway, activation of FZDs triggering the Wnt signaling cascade is frequently observed in human tumors and intimately associated with an aggressive carcinoma phenotype. It has been shown that the abnormal expression of FZD receptors contributes to the manifestation of malignant characteristics in human tumors such as enhanced cell proliferation, metastasis, chemotherapy resistance as well as the acquisition of cancer stemness. Given the essential roles of FZD receptors in the Wnt signaling in human tumors, this review aims to consolidate the prevailing knowledge on the specific status of FZD receptors (FZD1-10) and elucidate their respective functions in tumor progression. Furthermore, we delineate the structural basis for binding of FZD and its co-receptors to Wnt, and provide a better theoretical foundation for subsequent studies on related mechanisms. Finally, we describe the existing biological classes of small molecule-based FZD inhibitors in detail in the hope that they can provide useful assistance for design and development of novel drug candidates targeted FZDs.

8.
J Am Chem Soc ; 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38632847

RESUMO

Lithium metal batteries (LMB) have high energy densities and are crucial for clean energy solutions. The characterization of the lithium metal interphase is fundamentally and practically important but technically challenging. Taking advantage of synchrotron X-ray, which has the unique capability of analyzing crystalline/amorphous phases quantitatively with statistical significance, we study the composition and dynamics of the LMB interphase for a newly developed important LMB electrolyte that is based on fluorinated ether. Pair distribution function analysis revealed the sequential roles of the anion and solvent in interphase formation during cycling. The relative ratio between Li2O and LiF first increases and then decreases during cycling, suggesting suppressed Li2O formation in both initial and long extended cycles. Theoretical studies revealed that in initial cycles, this is due to the energy barriers in many-electron transfer. In long extended cycles, the anion decomposition product Li2O encourages solvent decomposition by facilitating solvent adsorption on Li2O which is followed by concurrent depletion of both. This work highlights the important role of Li2O in transitioning from an anion-derived interphase to a solvent-derived one.

9.
Bioresour Technol ; 400: 130697, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38614145

RESUMO

Effects of a phosphorus-solubilizing bacteria (PSB) Bacillus megatherium on growth and lipid production of Chlorella sorokiniana were investigated in synthesized swine wastewater with dissolved inorganic phosphorus (DIP), insoluble inorganic phosphorus (IIP), and organic phosphorus (OP). The results showed that the PSB significantly promoted the algal growth in OP and IIP, by 1.10 and 1.78-fold, respectively. The algal lipid accumulation was also greatly triggered, respectively by 4.39, 1.68, and 1.38-fold in DIP, IIP, and OP. Moreover, compared with DIP, OP improved the oxidation stability of algal lipid by increasing the proportion of saturated fatty acids (43.8 % vs 27.9 %), while the PSB tended to adjust it to moderate ranges (30.2-41.6 %). Further, the transcriptome analysis verified the OP and/or PSB-induced up-regulated genes involving photosynthesis, lipid metabolism, signal transduction, etc. This study provided novel insights to enhance microalgae-based nutrient removal combined with biofuel production in practical wastewater, especially with complex forms of phosphorus.

10.
Enzyme Microb Technol ; 178: 110447, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38626534

RESUMO

Clostridium butyricum (C. butyricum) represents a new generation of probiotics, which is beneficial because of its good tolerance and ability to produce beneficial metabolites, such as short-chain fatty acids and enzymes; however, its low enzyme activity limits its probiotic efficacy. In this study, a mutant strain, C. butyricum FZM 240 was obtained using carbon ion beam irradiation, which exhibited greatly improved enzyme production and tolerance. The highest filter paper, endoglucanase, and amylase activities produced by C. butyricum FZM 240 were 125.69 U/mL, 225.82 U/ mL, and 252.28 U/mL, which were 2.58, 1.95, and 2.21-fold higher, respectively, than those of the original strain. The survival rate of the strain increased by 11.40 % and 5.60 % after incubation at 90 °C for 5 min and with simulated gastric fluid at pH 2.5 for 2 h, respectively, compared with that of the original strain. Whole-genome resequencing and quantitative real-time PCR(qRT-PCR) analysis showed that the expression of genes related to enzyme synthesis (GE000348, GE001963 and GE003123) and tolerance (GE001114) was significantly up-regulated, while that of genes related to acid metabolism (GE003450) was significantly down-regulated. On this basis, homology modeling and functional prediction of the proteins encoded by the mutated genes were performed. According to the results, the properties related to the efficacy of C. butyricum as a probiotic were significantly enhanced by carbon ion beam irradiation, which is a novel strategy for the application of Clostridium spp. as feed additives.

11.
Structure ; 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38626767

RESUMO

Nectin and nectin-like (Necl) co-receptor axis, comprised of receptors DNAM-1, TIGIT, CD96, PVRIG, and nectin/Necl ligands, is gaining prominence in immuno-oncology. Within this axis, the inhibitory receptor PVRIG recognizes Nectin-2 with high affinity, but the underlying molecular basis remains unknown. By determining the crystal structure of PVRIG in complex with Nectin-2, we identified a unique CC' loop in PVRIG, which complements the double-lock-and-key binding mode and contributes to its high affinity for Nectin-2. The association of the corresponding charged residues in the F-strands explains the ligand selectivity of PVRIG toward Nectin-2 but not for Necl-5. Moreover, comprehensive comparisons of the binding capacities between co-receptors and ligands provide innovative insights into the intra-axis immunoregulatory mechanism. Taken together, these findings broaden our understanding of immune recognition and regulation mediated by nectin/Necl co-receptors and provide a rationale for the development of immunotherapeutic strategies targeting the nectin/Necl axis.

12.
Phys Chem Chem Phys ; 26(15): 11722-11730, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38563575

RESUMO

Ferrovalley materials hold great promise for implementation of logic and memory devices in valleytronics. However, there have so far been limited ferrovalley materials exhibiting significant valley polarization and high Curie temperature (TC). Using first-principles calculations, we predict that the TiTeBr monolayer is a promising ferrovalley candidate. It exhibits intrinsic ferromagnetism with TC as high as 220 K. It is indicated that an out-of-plane alignment of magnetization demonstrates a valley polarization up to 113 meV in the topmost valence band, as further verified by perturbation theory considering both the spin polarization and spin-orbit coupling. Under an in-plane electric field, the valley-dependent Berry curvature results in the anomalous valley Hall effect (AVHE). Moreover, under a suitable in-plane biaxial strain, the TiTeBr monolayer transforms into a Chern insulator with a nonzero Chern number, yet retains its ferrovalley characters and thus the emergent quantum anomalous valley Hall effect (QAVHE). Our study indicates that the TiTeBr monolayer is a promising ferrovalley material, and it provides a platform for investigating the valley-dependent Hall effect.

13.
Bioorg Med Chem Lett ; 105: 129741, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38599296

RESUMO

ZJ-101, a structurally simplified analog of marine natural product superstolide A, was previously designed and synthesized in our laboratory. In the present study four new analogs of ZJ-101 were designed and synthesized to investigate the structure-activity relationship of the acetamide moiety of the molecule. The biological evaluation showed that the amide moiety is important for the molecule's anticancer activity. Replacing the amide with other functional groups such as a sulfonamide group, a carbamate group, and a urea group resulted in the decrease in anticancer activity.

14.
Zhongguo Zhong Yao Za Zhi ; 49(4): 1007-1016, 2024 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-38621908

RESUMO

Chondrocytes are unique resident cells in the articular cartilage, and the pathological changes of them can lead to the occurrence of osteoarthritis(OA). Ligusticum cycloprolactam(LIGc) are derivatives of Z-ligustilide(LIG), a pharmacodynamic marker of Angelica sinensis, which has various biological functions such as anti-inflammation and inhibition of cell apoptosis. However, its protective effect on chondrocytes in the case of OA and the underlying mechanism remain unclear. This study conducted in vitro experiments to explore the molecular mechanism of LIGc in protecting chondrocytes from OA. The inflammation model of rat OA chondrocyte model was established by using interleukin-1ß(IL-1ß) to induce. LIGc alone and combined with glycyrrhizic acid(GA), a blocker of the high mobility group box-1 protein(HMGB1)/Toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB) signaling pathway, were used to intervene in the model, and the therapeutic effects were systematically evaluated. The viability of chondrocytes treated with different concentrations of LIGc was measured by the cell counting kit-8(CCK-8), and the optimal LIGc concentration was screened out. Annexin V-FITC/PI apoptosis detection kit was employed to examine the apoptosis of chondrocytes in each group. The enzyme-linked immunosorbent assay(ELISA) was employed to measure the expression of cyclooxygenase-2(COX-2), prostaglandin-2(PGE2), and tumor necrosis factor-alpha(TNF-α) in the supernatant of chondrocytes in each group. Western blot was employed to determine the protein levels of B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), caspase-3, HMGB1, TLR4, and NF-κB p65. The mRNA levels of HMGB1, TLR4, NF-κB p65, and myeloid differentiation factor 88(MyD88) in chondrocytes were determined by real-time fluorescent quantitative PCR(RT-qPCR). The safe concentration range of LIGc on chondrocytes was determined by CCK-8, and then the optimal concentration of LIGc for exerting the effect was clarified. Under the intervention of IL-1ß, the rat chondrocyte model of OA was successfully established. The modeled chondrocytes showed increased apoptosis rate, promoted expression of COX-2, PGE2, and TNF-α, up-regulated protein levels of Bax, caspase-3, HMGB1, TLR4, and NF-κB p65 and mRNA levels of HMGB1, TLR4, NF-κB p65, and MyD88, and down-regulated protein level of Bcl-2. However, LIGc reversed the IL-1ß-induced changes of the above factors. Moreover, LIGc combined with GA showed more significant reversal effect than LIGc alone. These fin-dings indicate that LIGc extracted and derived from the traditional Chinese medicine A. sinensis can inhibit the inflammatory response of chondrocytes and reduce the apoptosis of chondrocytes, and this effect may be related to the HMGB1/TLR4/NF-κB signaling pathway. The pharmacological effect of LIGc on protecting chondrocytes has potential value in delaying the progression of OA and improving the clinical symptoms of patients, and deserves further study.


Assuntos
Proteína HMGB1 , Ligusticum , Osteoartrite , Humanos , Ratos , Animais , NF-kappa B/genética , NF-kappa B/metabolismo , Condrócitos , Caspase 3/metabolismo , Proteína X Associada a bcl-2/metabolismo , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Proteína HMGB1/genética , Proteína HMGB1/metabolismo , Proteína HMGB1/farmacologia , Dinoprostona , Fator 88 de Diferenciação Mieloide/metabolismo , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Transdução de Sinais , Inflamação/metabolismo , Osteoartrite/tratamento farmacológico , Osteoartrite/genética , Apoptose , RNA Mensageiro/metabolismo
15.
Cell Stem Cell ; 31(4): 554-569.e17, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38579685

RESUMO

The YAP/Hippo pathway is an organ growth and size regulation rheostat safeguarding multiple tissue stem cell compartments. LATS kinases phosphorylate and thereby inactivate YAP, thus representing a potential direct drug target for promoting tissue regeneration. Here, we report the identification and characterization of the selective small-molecule LATS kinase inhibitor NIBR-LTSi. NIBR-LTSi activates YAP signaling, shows good oral bioavailability, and expands organoids derived from several mouse and human tissues. In tissue stem cells, NIBR-LTSi promotes proliferation, maintains stemness, and blocks differentiation in vitro and in vivo. NIBR-LTSi accelerates liver regeneration following extended hepatectomy in mice. However, increased proliferation and cell dedifferentiation in multiple organs prevent prolonged systemic LATS inhibition, thus limiting potential therapeutic benefit. Together, we report a selective LATS kinase inhibitor agonizing YAP signaling and promoting tissue regeneration in vitro and in vivo, enabling future research on the regenerative potential of the YAP/Hippo pathway.


Assuntos
Inibidores de Proteínas Quinases , Proteínas Serina-Treonina Quinases , Proteínas de Sinalização YAP , Animais , Humanos , Camundongos , Proliferação de Células , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/metabolismo , Células-Tronco/metabolismo , Fatores de Transcrição/metabolismo , Proteínas de Sinalização YAP/agonistas , Proteínas de Sinalização YAP/efeitos dos fármacos , Proteínas de Sinalização YAP/metabolismo , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacologia
16.
Sci Transl Med ; 16(741): eadj5705, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38569015

RESUMO

Cancer-associated fibroblasts (CAFs) are abundant stromal cells in the tumor microenvironment that promote cancer progression and relapse. However, the heterogeneity and regulatory roles of CAFs underlying chemoresistance remain largely unclear. Here, we performed a single-cell analysis using high-dimensional flow cytometry analysis and identified a distinct senescence-like tetraspanin-8 (TSPAN8)+ myofibroblastic CAF (myCAF) subset, which is correlated with therapeutic resistance and poor survival in multiple cohorts of patients with breast cancer (BC). TSPAN8+ myCAFs potentiate the stemness of the surrounding BC cells through secretion of senescence-associated secretory phenotype (SASP)-related factors IL-6 and IL-8 to counteract chemotherapy. NAD-dependent protein deacetylase sirtuin 6 (SIRT6) reduction was responsible for the senescence-like phenotype and tumor-promoting role of TSPAN8+ myCAFs. Mechanistically, TSPAN8 promoted the phosphorylation of ubiquitin E3 ligase retinoblastoma binding protein 6 (RBBP6) at Ser772 by recruiting MAPK11, thereby inducing SIRT6 protein destruction. In turn, SIRT6 down-regulation up-regulated GLS1 and PYCR1, which caused TSPAN8+ myCAFs to secrete aspartate and proline, and therefore proved a nutritional niche to support BC outgrowth. By demonstrating that TSPAN8+SIRT6low myCAFs were tightly associated with unfavorable disease outcomes, we proposed that the combined regimen of anti-TSPAN8 antibody and SIRT6 activator MDL-800 is a promising approach to overcome chemoresistance. These findings highlight that senescence contributes to CAF heterogeneity and chemoresistance and suggest that targeting TSPAN8+ myCAFs is a promising approach to circumvent chemoresistance.


Assuntos
Neoplasias da Mama , Fibroblastos Associados a Câncer , Sirtuínas , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Fibroblastos Associados a Câncer/metabolismo , Fibroblastos Associados a Câncer/patologia , Resistencia a Medicamentos Antineoplásicos , Recidiva Local de Neoplasia/patologia , Fibroblastos/patologia , Microambiente Tumoral , Proteínas de Ligação a DNA , Ubiquitina-Proteína Ligases , Tetraspaninas/genética , Tetraspaninas/metabolismo
17.
Biomed Pharmacother ; 174: 116523, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38574627

RESUMO

Inflammatory bowel disease is linked to a higher occurrence of bone loss. Oxyberberine can effectively improve experimental inflammatory bowel disease. However, no study has shown the effect of oxyberberine on inflammatory bowel disease induced bone loss. The present study was performed to investigate the role of oxyberberine in inflammatory bowel disease induced osteoporosis in chronic inflammatory bowel disease mice model. The inflammatory bowel disease mice were orally given two doses of oxyberberine daily. Blood, colon, and bone specimens were collected for biomarker assessments and histological examinations. Bone biomechanical properties and key proteins and genes involved in the receptor activator of nuclear factor kappa-B ligand/nuclear factor kappa-B signaling pathway were evaluated. Additionally, the binding characteristics of oxyberberine and receptor activator of nuclear factor kappa-B ligand were evaluated by in silico simulation. Results indicated that oxyberberine treatment significantly attenuated the macroscopic damage, colonic shortening, and histological injury from the colon. Furthermore, oxyberberine decreased serum inflammatory cytokine levels. The intervention with oxyberberine significantly mitigated the deterioration of bone mass, biomechanical properties, and microstructural parameters. Moreover, the upregulated osteoclast formation factors in model mice were significantly abolished by oxyberberine. In silico simulation results also showed that oxyberberine was firmly bound with target protein. Hence, our findings indicated that oxyberberine had the potential to mitigate inflammatory bowel disease induced inflammation in bone, inhibit osteoclast formation through regulating the receptor activator of nuclear factor kappa-B ligand/nuclear factor kappa-B signaling pathway, and might be a valuable approach in preventing bone loss associated with inflammatory bowel disease.

18.
JAMA Intern Med ; 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38558109

RESUMO

This case report describes a patient in their 70s presenting to the hospital with dyspnea and fatigue.

19.
Lung Cancer ; 191: 107558, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38569278

RESUMO

OBJECTIVES: Mediastinal neoplasms are typical but uncommon thoracic diseases with increasing incidence and unfavorable prognoses. A comprehensive understanding of their spatiotemporal distribution is essential for accurate diagnosis and timely treatment. However, previous studies are limited in scale and data coverage. Therefore, this study aims to elucidate the distribution of mediastinal lesions, offering valuable insights into this disease. MATERIALS AND METHODS: This multi-center, hospital-based observational study included 20 nationwide institutions. A retrospective search of electronic medical records from January 1st, 2009, to December 31st, 2020, was conducted, collecting sociodemographic data, computed tomography images, and pathologic diagnoses. Analysis focused on age, sex, time, location, and geographical region. Comparative assessments were made with global data from a multi-center database. RESULTS: Among 7,765 cases, thymomas (30.7%), benign mediastinal cysts (23.4%), and neurogenic tumors (10.0%) were predominant. Distribution varied across mediastinal compartments, with thymomas (39.6%), benign cysts (28.1%), and neurogenic tumors (51.9%) most prevalent in the prevascular, visceral, and paravertebral mediastinum, respectively. Age-specific variations were notable, with germ cell tumors prominent in patients under 18 and aged 18-29, while thymomas were more common in patients over 30. The composition of mediastinal lesions across different regions of China remained relatively consistent, but it differs from that of the global population. CONCLUSION: This study revealed significant heterogeneity in the spatiotemporal distribution of mediastinal neoplasms. These findings provide useful demographic data when considering the differential diagnosis of mediastinal lesions, and would be beneficial for tailoring disease prevention and control strategies.

20.
J Gastrointest Surg ; 2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38570232

RESUMO

BACKGROUND: Although preoperative neoadjuvant chemotherapy (NACT) or chemoradiation is the current standard of care for esophageal cancer in China, the impact of subsequent adjuvant therapy on patient prognosis remains unknown. This study aims to analyze the effect of adjuvant chemotherapy (ACT) on the survival rates of patients who have achieved a non-pathological complete response (non-pCR) after NACT and subsequent surgery. METHODS: We reviewed the data of 2193 patients with locally advanced thoracic esophageal squamous cell carcinoma (ESCC) who underwent radical surgery between January 2006 and January 2016. Of these patients, 46 received NACT and ACT, while 109 received NACT only. Propensity score matching was used to compare 86 patients, with 43 patients in the NACT + ACT group and 43 patients in the NACT group. Univariate analysis was performed using the Kaplan-Meier method and log-rank test, while Cox regression analysis was used for multivariate analysis. RESULTS: Multivariate analysis revealed that pathological lymph node status (positive vs negative) (P < .001) and treatment modalities (NACT + ACT vs NACT) (P = .005) were independent prognostic factors. There was a significant difference in long-term survival rates between the NACT + ACT and NACT groups, with 5-year survival rates of 55.8% vs 39.5%, respectively (c2 = 4.270, P = .039). In patients with ypN+ status, the 5-year survival rate was 31.8% for those who received ACT after NACT and surgery, compared to 10.0% for those who did not receive additional ACT (c2 = 6.101, P = .014). The corresponding percentages in patients with ypN- were 81.0% and 65.2%, respectively (c2 = 1.993, P = .158). CONCLUSION: Adjuvant chemotherapy should be recommended for locally advanced ESCC patients with residual cancer after NACT and surgery, especially for patients with nodal metastases after NACT.

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