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1.
Front Plant Sci ; 15: 1431097, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38947949

RESUMEN

Tender bamboo shoots undergo rapid senescence that influences their quality and commercial value after harvest. In this study, the tender sweet bamboo shoots ('Wensun') were packed by a passive modified atmosphere packaging (PMAP) to inhibit the senescence process, taking polyethylene package as control. The increase in CO2 and the decrease in O2 gas concentrations in the headspace atmosphere of the packages were remarkably modified by PMAP treatments. The modified gas atmosphere packaging inhibited the changes in firmness, as well as the content of cellulose, total pectin, and lignin in the cell walls of bamboo shoots. The enzymatic activities of cellulase, pectinase, and polygalacturonase that act on cell wall polysaccharides, and phenylalanine ammonia lyase, cinnamyl alcohol dehydrogenase, peroxidase, and laccase regulating the lignin biosynthesis were modified by PMAP treatment different from control during storage. The expression levels of the lignin biosynthesis genes PePAL3/4, PeCAD, Pe4CL5, PeC4H, PeCCOAOMT, PeCOMT, cellulose synthase PeCESA1, and related transcription factors PeSND2, PeKNAT7, PeMYB20, PeMYB63, and PeMYB85 were clearly regulated. These results suggest that PMAP efficiently retards the changes in lignin and cell wall polysaccharides, thus delaying the senescence of tender sweet bamboo shoots during storage.

2.
World J Gastrointest Oncol ; 16(6): 2271-2283, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38994170

RESUMEN

The morbidity and mortality of gastrointestinal (GI) malignancies are among the highest in the world, posing a serious threat to human health. Because of the insidious onset of the cancer, it is difficult for patients to be diagnosed at an early stage, and it rapidly progresses to an advanced stage, resulting in poor treatment and prognosis. Fusobacterium nucleatum (F. nucleatum) is a gram-negative, spore-free anaerobic bacterium that primarily colonizes the oral cavity and is implicated in the development of colorectal, esophageal, gastric, and pancreatic cancers via various intricate mechanisms. Recent development in novel research suggests that F. nucleatum may function as a biomarker in GI malignancies. Detecting the abundance of F. nucleatum in stool, saliva, and serum samples of patients may aid in the diagnosis, risk assessment, and prognosis monitoring of GI malignancies. This editorial systematically describes the biological roles and mechanisms of F. nucleatum in GI malignancies focusing on the application of F. nucleatum as a biomarker in the diagnosis and prognosis of GI malignancies to promote the clinical translation of F. nucleatum and GI tumors-related research.

3.
Res Sq ; 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38978583

RESUMEN

The rapid onset of innate immune defenses is critical for early control of viral replication in an infected host, yet it can also lead to irreversible tissue damage, especially in the respiratory tract. Intricate regulatory mechanisms must exist that modulate inflammation, while controlling the infection. Here, B cells expressing choline acetyl transferase (ChAT), an enzyme required for production of the metabolite and neurotransmitter acetylcholine (ACh) are identified as such regulators of the immediate early response to influenza A virus. Lung tissue ChAT + B cells are shown to interact with a7 nicotinic Ach receptor-expressing lung interstitial macrophages in mice within 24h of infection to control their production of TNFa, shifting the balance towards reduced inflammation at the cost of enhanced viral replication. Thus, innate-stimulated B cells are key participants of an immediate-early regulatory cascade that controls lung tissue damage after viral infection.

4.
Antioxidants (Basel) ; 13(7)2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-39061885

RESUMEN

Despite mounting evidence for dietary protease benefits, the mechanisms beyond enhanced protein degradation are poorly understood. This study aims to thoroughly investigate the impact of protease addition on the growth performance, intestinal function, and microbial composition of weaned piglets. Ninety 28-day-old weaned pigs were randomly assigned to the following three experimental diets based on their initial body weight for a 28-day experiment: (1) control (CC), a basic diet with composite enzymes without protease; (2) negative control (NC), a diet with no enzymes; and (3) dietary protease (PR), a control diet with protease. The results show that dietary proteases significantly enhanced growth performance and boosted antioxidant capacity, increasing the total antioxidant capacity (T-AOC) levels (p < 0.05) while reducing malonaldehyde levels (p < 0.05). Additionally, protease addition reduced serum levels of inflammatory markers TNF-α, IL-1ß, and IL-6 (p < 0.05), suppressed mRNA expression of pro-inflammatory factors in the jejunum (p < 0.01), and inhibited MAPK and NF-κB signaling pathways. Moreover, protease-supplemented diets improved intestinal morphology and barrier integrity, including zonula occludens protein 1(ZO-1), Occludin, and Claudin-1 (p < 0.05). Microbiota compositions were also significantly altered by protease addition with increased abundance of beneficial bacteria (Lachnospiraceae_AC2044_group and Prevotellaceae_UCG-001) (p < 0.05) and reduced harmful Terrisporobacter (p < 0.05). Further correlation analysis revealed a positive link between beneficial bacteria and growth performance and a negative association with inflammatory factors and intestinal permeability. In summary, dietary protease addition enhanced growth performance in weaned piglets, beneficial effects which were associated with improved intestinal barrier integrity, immunological response, and microbiota composition.

5.
Sci Rep ; 14(1): 16745, 2024 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-39033185

RESUMEN

Patchouli alcohol (PA) is a widely used pharmaceutical ingredient in various Chinese traditional herbal medicine (THM) formulations, known for its modulatory effects on the gut microbiota. The present study investigated PA's anti-inflammatory and regulatory effects on gut microbiota and its mode of action (MOA). Based on the assessments of ulcerative colitis (UC) symptoms, PA exhibited promising preventions against inflammatory response. In accordance, the expressions of pro-inflammatory factors, including interleukin (IL)-1ß, IL-6, tumor necrosis factor-α, and chemokine ligand 5 were significantly attenuated under PA treatment. Furthermore, PA enhanced the intestinal barrier damage caused by dextran sodium sulfate (DSS). Interestingly, PA exhibited negligible inventions on DSS-induced gut microbiota dysbiosis. PA did not affect the diversity of the DSS gut microbiota, it did alter the composition, as evidenced by a significant increase in the Firmicutes-Bacteroidetes (F/B) ratio. Finally, the MOA of PA against inflammation in DSS-treated mice was addressed by suppressing the expressions of heme oxygenase-1 (HO-1) and inducible nitric oxide synthase (iNOS). In conclusion, PA prevented inflammatory response in the DSS-induced UC mice model via directly suppressing HO-1 and iNOS-associated antioxidant signal pathways, independent of its effects on gut microbiota composition.


Asunto(s)
Colitis Ulcerosa , Sulfato de Dextran , Modelos Animales de Enfermedad , Microbioma Gastrointestinal , Sesquiterpenos , Animales , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/microbiología , Colitis Ulcerosa/metabolismo , Ratones , Microbioma Gastrointestinal/efectos de los fármacos , Sesquiterpenos/farmacología , Hemo-Oxigenasa 1/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Masculino , Antiinflamatorios/farmacología , Disbiosis/inducido químicamente , Disbiosis/microbiología , Ratones Endogámicos C57BL , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico
6.
Chem Sci ; 15(29): 11428-11434, 2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-39054998

RESUMEN

The mild catalytic generation of ketyl radicals for organic transformations remains an unsolved issue, although it facilitates the discovery of metal-catalyzed reactions with the features of high functional group tolerance. Here, we report the generation of the ketyl radicals and coupling with alkynes that was enabled by cost-effective chromium catalysis, allowing for the formation of valuable E-exocyclic allyl alcohols with high stereo- and chemoselectivity. A broad range of synthetically useful functional groups that are sensitive to strong reductants are compatible with the catalytic system, providing access to diverse substituted E-exocyclic allyl alcohols under mild conditions. Appended hydroxyl groups in products are facilely late-stage functionalized in accessing numerous derivatives, as well as the enantio-enrichment of exocyclic allyl alcohol using chiral ligands. Mechanistic studies suggest that bipyridine-ligated Cr(ii) complex serves as a reactive catalyst enabling the generation of the ketyl radical for coupling, giving vinyl radical, followed by the combination of Cr and transmetalation with Cp2ZrCl moiety in affording oxazirconiumacycle. This reaction provides a new opportunity for the mild formation of transient ketyl radicals from widely accessible aliphatic aldehydes for coupling with Earth-abundant metal catalysis.

7.
Nat Commun ; 15(1): 6455, 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39085244

RESUMEN

Coupling by metal-carbene transfer enables the formation of several different bonds at the carbenoid site, enabling prochiral Csp3 centers that are fundamental three-dimensional substructures for medicines to be forged with increased efficiency. However, strategies using bulk chemicals are rare because of the challenge of breaking two unactivated geminal bonds. Herein, we report the reactivity of ethers to form metal-carbene intermediate by cleavage of α-Csp3-H/Csp3-O bonds, which achieve selective coupling with arylmagnesium bromides and chlorosilanes. These couplings are catalysed by cyclic (alkyl)(amino)carbene-chromium complex and enable the one-step formation of 1,n-arylsilyl alcohols and α-arylated silanes. Mechanistic studies indicate that the in-situ formed low-valent Cr might react with iodobenzene to form phenyl radical species, which abstracts the α-H atom of ether in giving α-oxy radical. The latter combines with Cr by breaking α-Csp3-O bond to afford metal-carbene intermediate, which couples with aryl Grignard and chlorosilane to form two σ-bonds.

8.
Adv Mater ; : e2404734, 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39081101

RESUMEN

The van der Waals (vdW) interface provides two important degrees of freedom-twist and slip-to tune interlayer structures and inspire unique physics. However, constructing diversified high-quality slip stackings (i.e., lattice orientations between layers are parallel with only interlayer sliding) is more challenging than twisted stackings due to angstrom-scale structural discrepancies between different slip stackings, sparsity of thermodynamically stable candidates and insufficient mechanism understanding. Here, using transition metal dichalcogenide (TMD) homobilayers as a model system, this work theoretically elucidates that vdW materials with low lattice symmetry and weak interlayer coupling allow the creation of multifarious thermodynamically advantageous slip stackings, and experimentally achieves 13 and 9 slip stackings in 1T″-ReS2 and 1T″-ReSe2 bilayers via direct growth, which are systematically revealed by atomic-resolution scanning transmission electron microscopy (STEM), angle-resolved polarization Raman spectroscopy, and second harmonic generation (SHG) measurements. This work also develops modulation strategies to switch the stacking via grain boundaries (GBs) and to expand the slip stacking library from thermodynamic to kinetically favored structures via in situ thermal treatment. Finally, density functional theory (DFT) calculations suggest a prominent dependence of the pressure-induced electronic band structure transition on stacking configurations. These studies unveil a unique vdW epitaxy and offer a viable means for manipulating interlayer atomic registries.

9.
Theranostics ; 14(8): 3282-3299, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38855179

RESUMEN

Rationale: Pharmacological targeting of mitochondrial ion channels is developing as a new direction in cancer therapy. The opening or closing of these channels can impact mitochondrial function and structure by interfering with intracellular ion homeostasis, thereby regulating cell fate. Nevertheless, their abnormal expression or regulation poses challenges in eliminating cancer cells, and further contributes to metastasis, recurrence, and drug resistance. Methods: We developed an engineered mitochondrial targeted delivery system with self-reinforcing potassium ion (K+) influx via amphiphilic mitochondrial targeting polymer (TMP) as carriers to co-deliver natural K+ channel agonists (Dinitrogen oxide, DZX) and artificial K+ channel molecules (5F8). Results: Using this method, DZX specifically activated natural K+ channels, whereas 5F8 assembled artificial K+ channels on the mitochondrial membrane, leading to mitochondrial K+ influx, as well as oxidative stress and activation of the mitochondrial apoptotic pathway. Conclusion: The synergistic effect of 5F8 and DZX presents greater effectiveness in killing cancer cells than DZX alone, and effectively inhibited tumor recurrence and lung metastasis following surgical resection of breast cancer tumors in animal models. This strategy innovatively integrates antihypertensive drugs with artificial ion channel molecules for the first time to effectively inhibit tumor recurrence and metastasis by disrupting intracellular ion homeostasis, which will provide a novel perspective for postoperative tumor therapy.


Asunto(s)
Homeostasis , Mitocondrias , Animales , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Humanos , Homeostasis/efectos de los fármacos , Ratones , Línea Celular Tumoral , Femenino , Recurrencia Local de Neoplasia/prevención & control , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Apoptosis/efectos de los fármacos , Potasio/metabolismo , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/secundario , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Ratones Endogámicos BALB C , Canales Iónicos/metabolismo , Canales de Potasio/metabolismo , Ratones Desnudos , Metástasis de la Neoplasia
10.
Cell Host Microbe ; 32(7): 1103-1113.e6, 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38838675

RESUMEN

Antibiotic treatment promotes the outgrowth of intestinal Candida albicans, but the mechanisms driving this fungal bloom remain incompletely understood. We identify oxygen as a resource required for post-antibiotic C. albicans expansion. C. albicans depleted simple sugars in the ceca of gnotobiotic mice but required oxygen to grow on these resources in vitro, pointing to anaerobiosis as a potential factor limiting growth in the gut. Clostridia species limit oxygen availability in the large intestine by producing butyrate, which activates peroxisome proliferator-activated receptor gamma (PPAR-γ) signaling to maintain epithelial hypoxia. Streptomycin treatment depleted Clostridia-derived butyrate to increase epithelial oxygenation, but the PPAR-γ agonist 5-aminosalicylic acid (5-ASA) functionally replaced Clostridia species to restore epithelial hypoxia and colonization resistance against C. albicans. Additionally, probiotic Escherichia coli required oxygen respiration to prevent a post-antibiotic bloom of C. albicans, further supporting the role of oxygen in colonization resistance. We conclude that limited access to oxygen maintains colonization resistance against C. albicans.


Asunto(s)
Candida albicans , Oxígeno , Candida albicans/efectos de los fármacos , Animales , Ratones , Oxígeno/metabolismo , PPAR gamma/metabolismo , Antibacterianos/farmacología , Escherichia coli/efectos de los fármacos , Candidiasis/microbiología , Anaerobiosis , Hipoxia/metabolismo , Ratones Endogámicos C57BL , Estreptomicina/farmacología , Humanos , Ciego/microbiología , Mucosa Intestinal/microbiología , Mucosa Intestinal/metabolismo , Vida Libre de Gérmenes
11.
J Steroid Biochem Mol Biol ; 242: 106547, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38754522

RESUMEN

Premature ovarian insufficiency (POI) presents a substantial challenge to women's physiological and psychological well-being. Hormone replacement therapy, as the preferred therapeutic approach, involves solely exogenous supplementation of estrogen. Moxibustion, a traditional Chinese external treatment, has been investigated in our previous studies. It not only improves hormone levels and clinical symptoms in POI patients but also safeguards ovarian reserve. This study aims to explore the regulatory mechanisms by which moxibustion modulates hormone levels and restores ovarian function in POI. A POI rat model was established using cyclophosphamide, and moxibustion treatment was applied at acupoints "CV4" and "SP6" for a total of four courses. Subsequently, ovaries from each group were subjected to transcriptome sequencing (Bulk RNA-seq). Target pathways and key genes were selected through enrichment analysis and GSVA scoring, with validation using various techniques including electron microscopy, ELISA, Western blot, and immunohistochemistry. The results demonstrated that moxibustion restored the estrous cycle in POI rats, improved sex hormone levels, reduced the number of atretic follicles, and increased the count of dominant follicles (P<0.05). Bulk RNA-seq analysis revealed that moxibustion downregulated pathways associated with ovarian dysfunction, infertility, and immune responses, upregulated pathways related to follicular development and ovarian steroidogenesis. Furthermore, our data confirmed that moxibustion significantly increased the number of ovarian granulosa cells (GCs) and upregulated the expression of proteins related to steroidogenesis in GCs, including FSHR, P450 arom, cAMP, PKA, and CREB (P<0.05), with no significant effect observed on proteins related to steroidogenesis in theca cells. These outcomes aligned with the RNA-seq results. In conclusion, these findings propose that moxibustion enhances steroidogenesis in GCs through the activation of the cAMP/PKA/CREB pathway, consequently improving impaired ovarian function in POI rats. This study provides robust evidence supporting moxibustion as a targeted intervention for treating POI by specifically regulating steroidogenesis in GCs.


Asunto(s)
Proteína de Unión a Elemento de Respuesta al AMP Cíclico , Proteínas Quinasas Dependientes de AMP Cíclico , AMP Cíclico , Células de la Granulosa , Moxibustión , Insuficiencia Ovárica Primaria , Animales , Femenino , Ratas , AMP Cíclico/metabolismo , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/genética , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Proteínas Quinasas Dependientes de AMP Cíclico/genética , Células de la Granulosa/metabolismo , Ovario/metabolismo , Insuficiencia Ovárica Primaria/terapia , Insuficiencia Ovárica Primaria/metabolismo , Insuficiencia Ovárica Primaria/genética , Ratas Sprague-Dawley , Transducción de Señal
12.
Zhongguo Zhong Yao Za Zhi ; 49(8): 2178-2187, 2024 Apr.
Artículo en Chino | MEDLINE | ID: mdl-38812233

RESUMEN

This paper aims to explore the effect of Xuming Decoction in the Records of Proved Prescriptions, Ancient and Modern on cerebral ischemic injury and angiogenesis in the rat model of acute cerebral infarction. SD rats were randomized into 6 groups: sham group, model group, low-, medium-, and high-dose(5.13, 10.26, and 20.52 g·kg~(-1), respectively) Xuming Decoction groups, and butylphthalide(0.06 g·kg~(-1)) group. After the successful establishment of the rat model by middle cerebral artery occlusion(MCAO), rats in the sham and model groups were administrated with distilled water and those in other groups with corresponding drugs for 7 consecutive days. After the neurological function was scored, all the rats were sacrificed, and the brain tissue samples were collected. The degree of cerebral ischemic injury was assessed by the neurological deficit score and staining with 2,3,5-triphenyltetrazolium chloride. Hematoxylin-eosin staining was performed to observe the pathological changes in the brain. Transmission electron microscopy was employed to observe the ultrastructures of neurons and microvascular endothelial cells(ECs) on the ischemic side of the brain tissue. Immunofluorescence assay was employed to detect the expression of von Willebrand factor(vWF) and hematopoietic progenitor cell antigen CD34(CD34) in the ischemic brain tissue. Real-time PCR and Western blot were employed to determine the mRNA and protein levels, respectively, of Runt-related transcription factor 1(RUNX1), vascular endothelial growth factor(VEGF), angiopoietin-1(Ang-1), angiopoietin-2(Ang-2), and VEGF receptor 2(VEGFR2) in the ischemic brain tissue. The results showed that compared with the sham group, the model group showed increased neurological deficit score and cerebral infarction area(P<0.01), pathological changes, and damaged ultrastructure of neurons and microvascular ECs in the ischemic brain tissue. Furthermore, the modeling up-regulated the mRNA levels of RUNX1, VEGF, Ang-1, Ang-2, and VEGFR2(P<0.01) and the protein levels of vWF, CD34, RUNX1, VEGF, Ang-1, Ang-2, and VEGFR2(P<0.05 or P<0.01). Compared with the model group, high-dose Xuming Decoction and butylphthalide decreased the neurological deficit score and cerebral infarction area(P<0.01) and alleviated the pathological changes and damage of the ultrastructure of neurons and microvascular ECs in the ischemic brain tissue. Moreover, they up-regulated the mRNA levels of RUNX1, VEGF, Ang-1, Ang-2, and VEGFR2(P<0.01) and the protein levels of vWF, CD34, RUNX1, VEGF, Ang-1, Ang-2, and VEGFR2(P<0.01). The results suggest that Xuming Decoction in the Records of Proved Prescriptions, Ancient and Modern can promote the angiogenesis and collateral circulation establishment to alleviate neurological dysfunction of the ischemic brain tissue in MCAO rats by regulating the RUNX1/VEGF pathway.


Asunto(s)
Isquemia Encefálica , Infarto Cerebral , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos , Ratas Sprague-Dawley , Animales , Ratas , Masculino , Medicamentos Herbarios Chinos/farmacología , Infarto Cerebral/tratamiento farmacológico , Infarto Cerebral/metabolismo , Infarto Cerebral/genética , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/metabolismo , Isquemia Encefálica/genética , Humanos , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismo , Neovascularización Fisiológica/efectos de los fármacos , Angiopoyetina 2/genética , Angiopoyetina 2/metabolismo , Angiogénesis
13.
Mycopathologia ; 189(3): 32, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38622365

RESUMEN

The rare fungus Candida saopaulonensis has never been reported to be associated with human infection. We report the draft genome sequence of the first clinical isolate of C. saopaulonensis, which was isolated from a very premature infant with sepsis. This is the first genome assembly reaching the near-complete chromosomal level with structural annotation for this species, opening up avenues for exploring evolutionary patterns and genetic mechanisms of pathogenesis.


Asunto(s)
Candida , Sepsis , Humanos , Recién Nacido , Candida/genética , Genoma Fúngico , Recien Nacido Prematuro
14.
Int J Pharm ; 657: 124126, 2024 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-38626845

RESUMEN

As the monotherapy of available analgesics is usually accompanied by serious side effects or limited efficacy in the management of chronic pain, multimodal analgesia is widely used to achieve improved benefit-to-risk ratios in clinic. Drug-drug salts are extensively researched to optimize the physicochemical properties of active pharmaceutical ingredients (APIs) and achieve clinical benefits compared with individual APIs or their combination. New drug-drug salt crystals metformin-ibuprofen (MET-IBU) and metformin-naproxen (MET-NAP) were prepared from metformin (MET) and two poorly water-soluble anti-inflammatory drugs (IBU and NAP) by the solvent evaporation method. The structures of these crystals were confirmed by single crystal and powder X-ray diffraction, Hirshfeld surface, Fourier transform infrared spectroscopy and thermal analysis. Both MET-IBU and MET-NAP showed significantly improved solubility and intrinsic dissolution rate than the pure IBU or NAP. The stability test indicated that MET-IBU and MET-NAP have excellent physical stability under stressing test (10 days) and accelerated conditions (3 months). Moreover, isobolographic analysis suggested that MET-IBU and MET-NAP exerted potent and synergistic antinociceptive effects in λ-Carrageenan-induced inflammatory pain in mice, and both of them had an advantage in rapid pain relief. These results demonstrated the potential of MET-IBU and MET-NAP to achieve synergistic antinociceptive effects by developing drug-drug salt crystals.


Asunto(s)
Analgésicos , Cristalización , Sinergismo Farmacológico , Ibuprofeno , Metformina , Naproxeno , Solubilidad , Metformina/química , Metformina/administración & dosificación , Metformina/farmacología , Animales , Naproxeno/química , Naproxeno/administración & dosificación , Ibuprofeno/química , Ibuprofeno/administración & dosificación , Ibuprofeno/farmacología , Analgésicos/química , Analgésicos/administración & dosificación , Analgésicos/farmacología , Ratones , Masculino , Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/farmacología , Dolor/tratamiento farmacológico , Estabilidad de Medicamentos , Carragenina , Liberación de Fármacos , Sales (Química)/química
15.
Chem Commun (Camb) ; 60(39): 5201-5204, 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38651837

RESUMEN

The defluoroborylation of fluoroarenes by chromium-catalyzed cleavage of unactivated C-F bonds is described. The reaction uses HBpin as the boron source, low-cost and commercially available chromium salt as the precatalyst, and terpyridine as a crucial ligand, providing a protocol with atom-efficient benefits and a wide range of applicable substrates for the functionalization of aryl C-F bonds. Preliminary mechanistic studies indicate that an unprecedented Cr-catalyzed magnesiation of the unactivated C-F bond occurred. The generated arylmagnesium intermediates then participated in the subsequent borylation reaction. The application of the strategy in the preparation of valuable derivatives is demonstrated by the late-stage functionalization of boronate ester groups.

16.
World J Gastrointest Oncol ; 16(3): 979-990, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38577474

RESUMEN

BACKGROUND: Helicobacter pylori (H. pylori) is the primary risk factor for gastric cancer (GC), the Wnt/ß-Catenin signaling pathway is closely linked to tumourigenesis. GC has a high mortality rate and treatment cost, and there are no drugs to prevent the progression of gastric precancerous lesions to GC. Therefore, it is necessary to find a novel drug that is inexpensive and preventive to against GC. AIM: To explore the effects of H. pylori and Moluodan on the Wnt/ß-Catenin signaling pathway and precancerous lesions of GC (PLGC). METHODS: Mice were divided into the control, N-methyl-N-nitrosourea (MNU), H. pylori + MNU, and Moluodan groups. We first created an H. pylori infection model in the H. pylori + MNU and Moluodan groups. A PLGC model was created in the remaining three groups except for the control group. Moluodan was fed to mice in the Moloudan group ad libitum. The general condition of mice were observed during the whole experiment period. Gastric tissues of mice were grossly and microscopically examined. Through quantitative real-time PCR (qRT-PCR) and Western blotting analysis, the expression of relevant genes were detected. RESULTS: Mice in the H. pylori + MNU group showed the worst performance in general condition, gastric tissue visual and microscopic observation, followed by the MNU group, Moluodan group and the control group. QRT-PCR and Western blotting analysis were used to detect the expression of relevant genes, the results showed that the H. pylori + MNU group had the highest expression, followed by the MNU group, Moluodan group and the control group. CONCLUSION: H. pylori can activate the Wnt/ß-catenin signaling pathway, thereby facilitating the development and progression of PLGC. Moluodan suppressed the activation of the Wnt/ß-catenin signaling pathway, thereby decreasing the progression of PLGC.

17.
Ecotoxicol Environ Saf ; 276: 116334, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38626607

RESUMEN

Thioacetamide (TAA) within the liver generates hepatotoxic metabolites that can be induce hepatic fibrosis, similar to the clinical pathological features of chronic human liver disease. The potential protective effect of Albiflorin (ALB), a monoterpenoid glycoside found in Paeonia lactiflora Pall, against hepatic fibrosis was investigated. The mouse hepatic fibrosis model was induced with an intraperitoneal injection of TAA. Hepatic stellate cells (HSCs) were subjected to treatment with transforming growth factor-beta (TGF-ß), while lipopolysaccharide/adenosine triphosphate (LPS/ATP) was added to stimulate mouse peritoneal macrophages (MPMs), leading to the acquisition of conditioned medium. For TAA-treated mice, ALB reduced ALT, AST, HYP levels in serum or liver. The administration of ALB reduced histopathological abnormalities, and significantly regulated the expressions of nuclear receptor-related 1 protein (NURR1) and the P2X purinoceptor 7 receptor (P2×7r) in liver. ALB could suppress HSCs epithelial-mesenchymal transition (EMT), extracellular matrix (ECM) deposition, and pro-inflammatory factor level. ALB also remarkably up-regulated NURR1, inhibited P2×7r signaling pathway, and worked as working as C-DIM12, a NURR1 agonist. Moreover, deficiency of NURR1 in activated HSCs and Kupffer cells weakened the regulatory effect of ALB on P2×7r inhibition. NURR1-mediated inhibition of inflammatory contributed to the regulation of ALB ameliorates TAA-induced hepatic fibrosis, especially based on involving in the crosstalk of HSCs-macrophage. Therefore, ALB plays a significant part in the mitigation of TAA-induced hepatotoxicity this highlights the potential of ALB as a protective intervention for hepatic fibrosis.


Asunto(s)
Células Estrelladas Hepáticas , Cirrosis Hepática , Miembro 2 del Grupo A de la Subfamilia 4 de Receptores Nucleares , Transducción de Señal , Tioacetamida , Animales , Tioacetamida/toxicidad , Células Estrelladas Hepáticas/efectos de los fármacos , Ratones , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/tratamiento farmacológico , Transducción de Señal/efectos de los fármacos , Masculino , Miembro 2 del Grupo A de la Subfamilia 4 de Receptores Nucleares/metabolismo , Miembro 2 del Grupo A de la Subfamilia 4 de Receptores Nucleares/genética , Hidrocarburos Aromáticos con Puentes/farmacología , Ratones Endogámicos C57BL , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Transición Epitelial-Mesenquimal/efectos de los fármacos
18.
Mol Plant Microbe Interact ; 37(6): 488-497, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38427716

RESUMEN

Gti1/Pac2 is a fungal-specific transcription factor family with a stable and conserved N-terminal domain. Generally, there are two members in this family, named Gti1/Wor1/Rpy1/Mit1/Reg1/Ros1/Sge1 and Pac2, which are involved in fungal growth, development, stress response, spore production, pathogenicity, and so on. The Gti1/Pac2 family proteins share some conserved and distinct functions. For example, in Schizosaccharomyces pombe, Gti1 promotes the initiation of gluconate uptake during glucose starvation, while Pac2 controls the onset of sexual development in a pathway independent of the cAMP cascade. In the last two decades, more attention was focused on the Gti1 and its orthologs because of their significant effect on morphological switching and fungal virulence. By contrast, limited work was published on the functions of Pac2, which is required for stress responses and conidiation, but plays a minor role in fungal virulence. In this review, we present an overview of our current understanding of the Gti1/Pac2 proteins that contribute to fungal development and/or pathogenicity and of the regulation mechanisms during infection related development. Understanding the working networks of the conserved Gti1/Pac2 transcription factors in fungal pathogenicity not only advances our knowledge of the highly elaborate infection process but may also lead to the development of novel strategies for the control of plant disease. [Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.


Asunto(s)
Proteínas Fúngicas , Estrés Fisiológico , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/genética , Virulencia , Hongos/patogenicidad , Hongos/metabolismo , Hongos/fisiología , Regulación Fúngica de la Expresión Génica , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Enfermedades de las Plantas/microbiología , Morfogénesis
19.
Heliyon ; 10(6): e27935, 2024 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-38515688

RESUMEN

Objectives: This study was aimed at analyzing the burden and trend of Alzheimer's disease and other dementias attributed to smoking (SADD) in the Belt and Road Initiative (BRI) countries during 1990-2019. Methods: Data from The 2019 Global Burden of Disease Study was used to extract information on the burden of SADD in terms of the numbers and age-standardized rate of mortality (ASMR) and disability-adjusted life years (ASDALR) in the BRI countries for 1990-2019. The average annual percent change (AAPC) was used to analyze the temporal trends of ASDALR from 1990 to 2019 and in the final decade by Joinpoint regression analysis. Results: The DALYs of SADD were the highest in China, India, and the Russian Federation in 1990 and in Lebanon, Montenegro and Bosnia, and Herzegovina in 2019. From 1990 to 2019, the ASDALR in China had increased from 55.50/105 to 66.18/105, but decreased from 2010 to 2019, while that of India had declined from 32.84/105 to 29.35/105, but increased from 2010 to 2019. The ASDALR showed the fastest increase in the Russian Federation, with AAPC of 1.97% (95% confidence interval [CI]: 1.77%, 2.16%), and the fastest decline in Sri Lanka, with AAPC of -2.69% (95% CI: 2.79%, -2.59%). ASMR and ASDALR from SADD showed a substantial decline during 1990-2019 both globally and in the different socio-demographic index (SDI) regions (all P < 0.05, except for the high-middle-SDI region). Compared to the rates in males, the AAPC in ASDALR of females was significantly greater in 20 countries(all P < 0.05). In the age group of 20-54 years, the DALYs rate showed a decreasing trend only in 13 members in the low-SDI region (all P < 0.05). Conclusion: Under the premise of eliminating the differences, mobilizing resources in the country itself, the BRI organization, and globally will help reduce the global SADD burden and achieve healthy and sustainable development.

20.
Nat Commun ; 15(1): 1138, 2024 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-38326391

RESUMEN

Two-dimensional (2D) semiconductor-based vertical-transport field-effect transistors (VTFETs) - in which the current flows perpendicularly to the substrate surface direction - are in the drive to surmount the stringent downscaling constraints faced by the conventional planar FETs. However, low-power device operation with a sub-60 mV/dec subthreshold swing (SS) at room temperature along with an ultra-scaled channel length remains challenging for 2D semiconductor-based VTFETs. Here, we report steep-slope VTFETs that combine a gate-controllable van der Waals heterojunction and a metal-filamentary threshold switch (TS), featuring a vertical transport channel thinner than 5 nm and sub-thermionic turn-on characteristics. The integrated TS-VTFETs were realised with efficient current switching behaviours, exhibiting a current modulation ratio exceeding 1 × 108 and an average sub-60 mV/dec SS over 6 decades of drain current. The proposed TS-VTFETs with excellent area- and energy-efficiency could help to tackle the performance degradation-device downscaling dilemma faced by logic transistor technologies.

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