Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 375
Filtrar
1.
Cureus ; 16(8): e66632, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39258062

RESUMO

BACKGROUND: The effectiveness of endodontic files relies significantly on the characteristics of the outermost layer, which can be greatly improved through suitable surface treatments and appropriate coatings. Graphene-based materials (GBMs) have been utilized to fabricate nanocomposite coatings aimed at improving surface characteristics and mechanical behavior, including resilience, sustainability, oxidation resistance, solidity, and traction. AIM: This research aims to study the surface topography of a nickel-titanium (Ni-Ti) pediatric rotary file coated with graphene oxide (GO) using a scanning electron microscope (SEM). METHODS: The study utilized Ni-Ti pediatric rotary instruments that were 16 mm long and had the same ISO tip size of #25. The Ni-Ti pediatric rotary files had a titanium oxide coating that needed to be removed for the application of the GO coating. The GO coating was applied to the files using an electrophoretic deposition (EPD) procedure. Data were gathered to evaluate the surface topography and structural profiles of the GO-coated endodontic files through SEM analysis. RESULTS: SEM imaging showed that the GO coatings consisted of numerous layers of GO sheets, which were uniformly and thoroughly applied to the endodontic instrument. A substantial portion of the GO layers aligned with neighboring layers along the edges, creating a continuous structure. CONCLUSION: GO coatings were effectively applied to Ni-Ti endodontic instruments using EPD. The deposition of the GO coating is consistent throughout the surface of the Ni-Ti rotary instrument.

2.
Gastrointest Endosc Clin N Am ; 34(4): 639-654, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39277296

RESUMO

Weight regain, also known as recurrent weight gain, is common following bariatric surgeries. While anti-obesity medications and surgical revisions offer effective treatment options, they are not without their challenges and limitations. Over the last few decades, there have been significant advancements in endoscopic interventions to address weight regain following bariatric surgery. These procedures have demonstrated feasibility, safety, efficacy, and durability, offering minimally invasive treatment options for this patient population.


Assuntos
Cirurgia Bariátrica , Aumento de Peso , Humanos , Cirurgia Bariátrica/métodos , Cirurgia Bariátrica/efeitos adversos , Endoscopia Gastrointestinal/métodos , Obesidade Mórbida/cirurgia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Recidiva , Obesidade/cirurgia
3.
Eur J Pharm Biopharm ; : 114506, 2024 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-39306200

RESUMO

Poor dissolution of axitinib (AXT) limits its effectiveness through the oral route. The present study investigated, prospective of liquisolid (LS) technology to improve dissolution rate and oral bioavailability of AXT to treat renal cell carcinoma. LS compacts were fabricated with PEG 200, Fujicalin SG, and Aerosil 200 as solvent, carrier, and coat material, respectively. The behavior of LS-systems during tabletting was investigated using Kawakita, Heckel, and Leuenberger analysis. LS compacts were examined for P-XRD, DSC, SEM, and in vitro drug dissolution. For optimization, a 32 full factorial design was utilized. Cell line A498 was utilized for in vitro cytotoxicity study. A bioavailability study was performed using rabbits. DSC and P-XRD analysis confirmed the transition of crystalline AXT to its partial amorphization and molecular dispersion. Consequently, LS6 demonstrated a significantly rapid drug dissolution (Q20; >99 %) than the directly compressed tablets (18.05 %). Additionally, 2.03-fold increase in oral bioavailability, and inhibited dose-dependent cell growth with 1.75-fold increased apoptosis rate. Overall, an LS6 compact consisting of 15 % AXT concentration in PEG 200 and a 20 w/w ratio of Fujicalin SG: Aerosil 200 exhibited improved formulation properties, enhanced dissolution rate, and bioavailability. Thus developed potential product may contribute low-cost production with patient-improved survival expectations.

4.
Biomark Res ; 12(1): 82, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39135109

RESUMO

Human trophoblastic cell surface antigen 2 (Trop2) is a glycoprotein, a cellular marker of trophoblastic and stem cells, and a calcium signaling transducer involved in several signaling pathways, leading to the proliferation, invasion, and metastasis of tumors. It is expressed at a low level in normal epithelial cells, but at a high level in many tumors, making it an ideal target for cancer therapy. According to previous literature, Trop2 is broadly expressed in all breast cancer subtypes, especially in triple negative breast cancer (TNBC). Several clinical trials have demonstrated the effectiveness of Trop2-targeted therapy in breast cancer. Sacituzumab govitecan (SG) is a Trop2-targeted antibody-drug conjugate (ADC) that has been approved for the treatment of metastatic TNBC and hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) breast cancer. This article reviews the structure and function of Trop2, several major Trop2-targeted ADCs, other appealing novel Trop2-targeted agents and relevant clinical trials to provide a landscape of how Trop2-targeted treatments will develop in the future.

5.
Sci Rep ; 14(1): 19419, 2024 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-39169087

RESUMO

Lignin syringyl to guaiacyl ratio (S/G) has long been suspected to have measurable impacts on biochar formation, but these effects are challenging to observe in biochars formed from whole biomass. When the model bioenergy feedstock Populus trichocarpa (cottonwood), with predictable lignin macromolecular structure tied to genetic variation, is used as feedstock for biochar production, these effects become visible. In this work, two P. trichocarpa variants having lignin S/G of 1.67 and 3.88 were ground and pyrolyzed at 700 °C. Water-demineralization of feedstock was used to simultaneously evaluate any synergistic influences of S/G and naturally-occurring potassium on biochar physicochemical properties and performance. The strongest effects of lignin S/G were observed on specific surface area (SBET) and oxygen-content, with S/G of 1.67 improving SBET by 11% and S/G of 3.88 increasing total oxygen content in demineralized biochars. Functional performance was evaluated by breakthrough testing in 1% NH3. Breakthrough times for biochars were nearly double that of a highly microporous activated carbon reference material, and biochar with S/G of 3.88 had 10% longer breakthrough time than its lower S/G corollary. Results support a combination of pore structure and oxygen-functionalities in controlling ammonia breakthrough for biochar.


Assuntos
Carvão Vegetal , Lignina , Populus , Carvão Vegetal/química , Lignina/química , Populus/química , Adsorção , Biomassa , Madeira/química
6.
Sci Rep ; 14(1): 17886, 2024 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-39095440

RESUMO

The precise extraction of winter wheat planting structure holds significant importance for food security risk assessment, agricultural resource management, and governmental decision-making. This study proposed a method for extracting the winter wheat planting structure by taking into account the growth phenology of winter wheat. Utilizing the fitting effect index, the optimal Savitzky-Golay (S-G) filtering parameter combination was determined automatically to achieve automated filtering and reconstruction of NDVI time series data. The phenological phases of winter wheat growth was identified automatically using a threshold method, and subsequently, a model for extracting the winter wheat planting structure was constructed based on three key phenological stages, including seeding, heading, and harvesting, with the combination of hierarchical classification principles. A priori sample library was constructed using historical data on winter wheat distribution to verify the accuracy of the extracted results. The validation of fitting effect on different surfaces demonstrated that the optimal filtering parameters for S-G filtering could be obtained automatically by using the fitting effect index. The extracted winter wheat phenological phases showed good consistency with ground-based observational results and MOD12Q2 phenological products. Validation against statistical yearbook data and the proposed priori knowledge base exhibited high statistical accuracy and spatial precision, with an extracting accuracy of 94.92%, a spatial positioning accuracy of 93.26%, and a kappa coefficient of 0.9228. The results indicated that the proposed method for winter wheat planting structure extracting can identify winter wheat areas rapidly and significantly. Furthermore, this method does not require training samples or manual experience, and exhibits strong transferability.


Assuntos
Estações do Ano , Triticum , Triticum/crescimento & desenvolvimento , Agricultura/métodos
7.
Antioxidants (Basel) ; 13(8)2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39199151

RESUMO

Radiation-induced salivary gland injury (RISGI) is a common complication of radiotherapy in patients with head and neck cancer. Intragland expression of the Sonic Hedgehog (Shh) gene may partially rescue irradiation (IR)-induced hyposalivation by preserving salivary stem/progenitor cells and parasympathetic innervation, maintaining resident macrophages, and maintaining microvascular density. Previous studies have revealed that Ad-Rat Shh transduction through the salivary glands of miniature pigs can ameliorate oxidative stress-induced microvascular dysfunction after radiotherapy. Changes in the parotid salivary flow rate were analyzed, and the parotid tissue was collected at 5 and 20 weeks after IR. Changes in the Hedgehog pathway and vascular function-related markers (vascular endothelial growth factor (VEGF) and CD31) and oxidative stress-related markers were detected via immunohistochemistry, immunofluorescence, and Western blotting. A stable Shh-overexpressing cell line was generated from human umbilical vein endothelial cells (HUVECs) and exposed to 10 Gy X-ray irradiation, after which endothelial cell proliferation, senescence, apoptosis, and vascular function were evaluated. We found that intragland expression of the Shh gene efficiently alleviated IR-induced parotid gland injury in a miniature pig model. Our results indicate that the antioxidative stress and microvascular-protective effects of the Hh pathway are regulated by nuclear factor-erythroid 2-related factor 2 (Nrf2).

8.
Obes Surg ; 34(9): 3324-3334, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39078450

RESUMO

PURPOSE: Mastering intracorporeal suturing is challenging in the evolution from conventional to laparoscopic bariatric surgery. Among various techniques competing for superiority in overcoming this hurdle, we focus on exploring the potential of barbed sutures through a meta-analysis that compares outcomes to those of conventional non-barbed sutures in bariatric surgery. MATERIALS AND METHODS: We conducted a comprehensive search on PubMed, Scopus, and Embase to identify studies comparing barbed sutures with non-barbed sutures in bariatric surgeries, focusing on outcomes such as operative time, suturing time, postoperative complications, and hospital stay. The statistical analysis was carried out using RStudio version 4.3.2. Heterogeneity was assessed using the Cochrane Q test and I2 statistics. RESULTS: Incorporating data from 11 studies involving a total of 27,442 patients, including 3,516 in the barbed suture group across various bariatric surgeries, our analysis demonstrates a significant reduction in suturing time (mean difference -4.87; 95% CI -8.43 to -1.30; p < 0.01; I2 = 99%) associated with the use of barbed sutures. Specifically, in Roux-en-Y gastric bypass, we observed a significant decrease in operative time (mean difference -12.11; 95% CI -19.27 to -4.95; p < 0.01; I2 = 93%). Subgroup analyses and leave-one-out analyses consistently supported these findings. Furthermore, we found that the mean body mass index did not significantly predict the mean difference in operative time outcome. No significant differences emerged in hospital stay or postoperative complications, including leak, bleeding, stenosis, and bowel obstruction (p > 0.05). CONCLUSION: Our study findings address barbed sutures as a potential alternative for laparoscopic intracorporeal suturing in bariatric surgery.


Assuntos
Cirurgia Bariátrica , Obesidade Mórbida , Duração da Cirurgia , Complicações Pós-Operatórias , Técnicas de Sutura , Suturas , Humanos , Cirurgia Bariátrica/efeitos adversos , Cirurgia Bariátrica/instrumentação , Cirurgia Bariátrica/métodos , Laparoscopia/métodos , Tempo de Internação/estatística & dados numéricos , Obesidade Mórbida/cirurgia , Complicações Pós-Operatórias/epidemiologia , Técnicas de Sutura/efeitos adversos , Técnicas de Sutura/instrumentação , Suturas/efeitos adversos , Resultado do Tratamento
9.
ACS Appl Bio Mater ; 7(8): 5290-5307, 2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39047188

RESUMO

The single-step synthesis of nitro-derivatized SG using dimethyldichlorosilane in an aprotic solvent dichloromethane at 300 K is efficient and straightforward. Reduction and diazotization effectively functionalize the material for enzyme coupling at the O-carbon of the enzyme's tyrosine. The high extraction efficiency of protonated dichromate ions with a breakthrough capacity of 480 µmol·g-1 is notable. Eco-friendly elution using distilled water achieves a significant enrichment factor of 23.2. Excellent reusability (up to 900 cycles) and stable sorption efficiency (ζ ≥ 0.9) highlight the material's potential for practical applications and future research.


Assuntos
Teste de Materiais , Papaína , Propriedades de Superfície , Papaína/química , Papaína/metabolismo , Aminas/química , Tamanho da Partícula , Estrutura Molecular , Materiais Biocompatíveis/química , Materiais Biocompatíveis/síntese química , Prótons
10.
Curr Probl Cardiol ; 49(10): 102760, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39059785

RESUMO

Atherosclerosis, a complex inflammatory and metabolic disorder, is the underlying cause of several life-threatening cardiovascular diseases. Stress granules (SG) are biomolecular condensates composed of proteins and mRNA that form in response to stress. Recent studies suggest a potential link between SG and atherosclerosis development. However, there remain gaps in understanding SG role in atherosclerosis development. Here we provide a thorough analysis of the role of SG in atherosclerosis, covering cellular stresses stimulation, core components, and regulatory genes in SG formation. Furthermore, we explore atherosclerosis induced factors such as inflammation, low or oscillatory shear stress (OSS), and oxidative stress (OS) may impact SG formation and then the development of atherosclerotic lesions. We have assessed how changes in SG dynamics impact pro-atherogenic processes like endothelial dysfunction, lipid metabolism, and immune cell recruitment in atherosclerosis. In summary, this review emphasizes the complex interplay between SG and atherosclerosis that could open innovative directions for targeted therapeutic strategies in preventing or treating atherosclerotic cardiovascular diseases.


Assuntos
Aterosclerose , Estresse Oxidativo , Grânulos de Estresse , Humanos , Aterosclerose/terapia , Aterosclerose/metabolismo , Aterosclerose/etiologia , Estresse Oxidativo/fisiologia , Grânulos de Estresse/metabolismo , Animais , Inflamação
11.
JSLS ; 28(2)2024.
Artigo em Inglês | MEDLINE | ID: mdl-38910956

RESUMO

Background and Objectives: Haemostasis-related complications associated with Medtronic Tri-stapleTM with preloaded buttress material and the novel, naked AEONTM gastrointestinal staplers have not been extensively studied in bariatric surgery. The study aimed to assess and compare the 30-day haemostasis-related complications between Medtronic Tri-stapleTM and AEONTM GIA staplers. Methods: A retrospective analysis was performed on data from patients who underwent primary or revision sleeve gastrectomy (SG) or the sleeve component of single anastomosis duodeno-ileal bypass with SG (SADI-S) in a private hospital in Australia between November 2021 and December 2022. The surgeries were performed by a single surgeon, using either Medtronic Tri-stapleTM or AEONTM staplers. Results: The analysis included 250 patients, with the first 125 consecutive patients receiving staple line using the Medtronic Tri-stapleTM GIA stapler and the subsequent 125 patients receiving staple line using the AEONTM GIA stapler. Statistical analysis revealed no significant differences in the distribution of surgical procedures between the Medtronic and AEON groups. In the AEON group, there were statistically higher numbers of diabetics and former tobacco users, while other preoperative characteristics did not significantly differ between the two groups. The AEON group had a significantly longer mean operative time, while the length of hospital stay was significantly shorter. No intraoperative or 30-day complications, deaths, emergency room visits, readmissions, or reoperations were observed in either group. Conclusion: The novel, naked AEONTM stapler demonstrated non-inferiority to the established Medtronic Tri-StapleTM with preloaded buttress material in achieving hemostasis and maintaining staple-line integrity in bariatric surgery.


Assuntos
Cirurgia Bariátrica , Grampeadores Cirúrgicos , Grampeamento Cirúrgico , Humanos , Estudos Retrospectivos , Feminino , Masculino , Cirurgia Bariátrica/métodos , Pessoa de Meia-Idade , Grampeamento Cirúrgico/métodos , Adulto , Obesidade Mórbida/cirurgia , Hemostasia Cirúrgica/instrumentação , Hemostasia Cirúrgica/métodos , Gastrectomia/métodos , Desenho de Equipamento
12.
Arch Microbiol ; 206(7): 308, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38896139

RESUMO

Prion-like proteins (PrLPs) have emerged as beneficial molecules with implications in adaptive responses. These proteins possess a conserved prion-like domain (PrLD) which is an intrinsically disordered region capable of adopting different conformations upon perceiving external stimuli. Owing to changes in protein conformation, functional characteristics of proteins harboring PrLDs get altered thereby, providing a unique mode of protein-based regulation. Since PrLPs are ubiquitous in nature and involved in diverse functions, through this study, we aim to explore the role of such domains in yet another important physiological process viz. plant-microbe interactions to get insights into the mechanisms dictating cross-kingdom interactions. We have evaluated the presence and functions of PrLPs in 18 different plant-associated fungi of agricultural importance to unravel their role in plant-microbe interactions. Of the 241,997 proteins scanned, 3,820 (~ 1.6%) were identified as putative PrLPs with pathogenic fungi showing significantly higher PrLP density than their beneficial counterparts. Further, through GO enrichment analysis, we could predict several PrLPs from pathogenic fungi to be involved in virulence and formation of stress granules. Notably, PrLPs involved in (retro)transposition were observed exclusively in pathogenic fungi. We even analyzed publicly available data for the expression alterations of fungal PrLPs upon their interaction with their respective hosts which revealed perturbation in the levels of some PrLP-encoding genes during interactions with plants. Overall, our work sheds light into the probable role of prion-like candidates in plant-fungi interaction, particularly in context of pathogenesis, paving way for more focused studies for validating their role.


Assuntos
Proteínas Fúngicas , Fungos , Plantas , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/genética , Proteínas Fúngicas/química , Plantas/microbiologia , Fungos/genética , Fungos/metabolismo , Fungos/patogenicidade , Simulação por Computador , Doenças das Plantas/microbiologia , Proteínas Priônicas/metabolismo , Proteínas Priônicas/genética , Proteínas Priônicas/química , Príons/metabolismo , Príons/genética , Príons/química , Virulência , Interações Hospedeiro-Patógeno
13.
Syst Appl Microbiol ; 47(4): 126522, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38852331

RESUMO

One of the numerous and widespread lineages of planctomycetes is the hitherto uncultured SG8-4 group inhabiting anoxic environments. A novel anaerobic, mesophilic, alkalitolerant, chemoorganotrophic bacterium (strain M17dextrT) was isolated from anaerobic sediment of a coastal lake (Taman Peninsula, Russia). The cell were mainly non-motile cocci, 0.3 to 1.0 µm in diameter forming chains or aggregates. The cells had a Gram-negative cell wall and divided by binary fission. The temperature range for growth was 20-37 0C (optimum at 30 0C). The pH range for growth was 6.5-10.0, with an optimum at pH 8.0-8.5. Strain M17dextrT fermented mono-, di- and polysaccharides (starch, xanthan gum, dextran, N-acetylglucosamine), but did not utilized proteinaceous compounds. Major cellular fatty acids were C16:0 and C18:0. The genome of strain M17dextrT had a size of 5.7 Mb with a G + C content of 62.49 %. The genome contained 345 CAZyme genes. The closest cultured phylogenetic relatives of strain M17dextrT were members of the order Sedimentisphaerales, class Phycisphaerae. Among characterized planctomycetes, the highest 16S rRNA gene sequence similarity (88.3 %) was observed with Anaerohalosphaera lusitana. According to phylogenomic analysis strain M17dextrT together with many uncultured representatives of Sedimentisphaerales forms a separate family-level lineage. We propose to assign strain M17dextrT to a novel genus and species, Anaerobaca lacustris gen. nov., sp. nov.; the type strain is M17dextrT (=VKM B-3571 T = DSM 113417 T = JCM 39238 T = KCTC 25381 T = UQM 41474 T). This genus is placed in a novel family, Anaerobacaceae fam. nov. within the order Sedimentisphaerales.


Assuntos
Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano , Ácidos Graxos , Lagos , Filogenia , Planctomycetales , RNA Ribossômico 16S , Análise de Sequência de DNA , Lagos/microbiologia , RNA Ribossômico 16S/genética , Ácidos Graxos/análise , Ácidos Graxos/química , DNA Bacteriano/genética , Planctomycetales/genética , Planctomycetales/classificação , Planctomycetales/isolamento & purificação , Federação Russa , Genoma Bacteriano/genética , Sedimentos Geológicos/microbiologia , Anaerobiose
14.
Front Bioeng Biotechnol ; 12: 1389127, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38751865

RESUMO

Introduction: Jones fractures frequently fail to unite, and adequate fixation stability is crucial. This study aimed to elucidate the biomechanical stability of various intramedullary screw fixation constructs. Methods: Jones fracture model over the proximal 5th metatarsal of artificial bone was created in all specimens. Six groups were divided based on varied screw constructs with different screw lengths, either 30 or 40 mm, including cannulated screws-C30 and C40 groups, one high-resistance suture combined with intramedullary cannulated screws (F.E.R.I. technique)-CF30 and CF40 groups, and second-generation headless compression screws (SG-HCS) -HL30 and HL40 groups. Mechanical testing was conducted sequentially, and the maximal force (N) and stiffness (N/mm) of all constructs were recorded. Results: The maximal force (N) at 1.0 mm downward displacement in C30, C40, CF30, CF40, HL30, and HL40 groups were 0.56 ± 0.02, 0.49 ± 0.02, 0.65 ± 0.02, 0.49 ± 0.01, 0.68 ± 0.02, and 0.73 ± 0.02, respectively, and the stiffness (N/mm) in subgroups were 0.49 ± 0.01, 0.43 ± 0.01, 0.67 ± 0.01, 0.42 ± 0.01, 0.61 ± 0.01, and 0.58 ± 0.02, respectively. SG-HCS subgroups exhibited greater maximal force and stiffness than conventional cannulated screws. Screws of 30 mm in length demonstrated better stability than all 40 mm-length screws in each subgroup. In C30 fixation, the stiffness and maximum force endured increased by 1.16 and 1.12 times, respectively, compared with the C40 fixation method. There were no significant differences between CF30 and SG-HCS groups. Only the F.E.R.I technique combined with the 4.5 mm cannulated screw of 30 mm in length increased the biomechanical stability for Jones fractures. Discussion: These biomechanical findings help clinicians decide on better screw fixation options for greater stability in Jones fractures, especially when large-diameter screws are limited in use. However, this biomechanical testing of intramedullary screw fixation on Jones fracture model lacks clinical validation and no comparisons to extramedullary plate fixations. Moving forward, additional clinical and biomechanical research is necessary to validate our findings.

15.
Spectrochim Acta A Mol Biomol Spectrosc ; 318: 124499, 2024 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-38788505

RESUMO

As a new type of persistent pollutant, microplastics pose a serious threat to the earth's ecological environment and human health. Efficient and reliable microplastic detection technology is of great significance in the management of microplastic pollution. Aiming at the problems of low signal-to-noise ratio (SNR), narrow spectral range and low spectral resolution in traditional microplastic detection technology, a splicing grating spatial heterodyne Raman spectroscopy (SG-SHRS) is proposed in this paper. The splicing grating is composed of four sub-gratings with groove densities of 320, 298, 276 and 254 gr / mm, respectively. Each sub-grating has an independent sub-filter to improve the SNR of the system. The system is simulated, built and calibrated. The actual resolution of the SG-SHRS system is 0.7 cm-1, and the spectral detection range of a single sub-grating is 2947.2 cm-1. Four kinds of microplastics, polyamide (PA), polystyrene (PS), polycarbonate (PC), and polyphenylene sulfide (PPS), were detected by the SG-SHRS system. The complete Raman spectral information of microplastics was obtained, and the peak assignment of Raman characteristic peaks of the four kinds of microplastics was analyzed. By comparing the test results with a commercial dispersion spectrometer, it has been proven that the SG-SHRS system has the advantages of high spectral resolution, wide spectral range, and high SNR, and has good application prospects in the field of microplastic detection.

16.
Braz J Microbiol ; 55(2): 1189-1203, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38705960

RESUMO

Alginate is a major extra polymeric substance in the biofilm formed by mucoid Pseudomonas aeruginosa. It is the main proven perpetrator of lung infections in patients suffering from cystic fibrosis. Alginate lyases are very important in the treatment of cystic fibrosis. This study evaluated the role of standalone and in conjugation, effect of alginate lyase of SG4 + isolated from Paenibacillus lautus in enhancing in vitro bactericidal activity of gentamicin and amikacin on mucoid P. aeruginosa. Using Response Surface Methodology (RSM) alginate lyase SG4 + production was optimized in shake flask and there 8.49-fold enhancement in enzyme production. In fermenter, maximum growth (10.15 mg/ml) and alginate lyase (1.46 International Units) production, 1.71-fold was increased using Central Composite Design (CCD). Further, fermentation time was reduced from 48 to 20 h. To the best of our knowledge this is the first report in which CCD was used for fermenter studies to optimize alginate lyase production. The Km and Vmax of purified enzyme were found to be 2.7 mg/ml and 0.84 mol/ml-min, respectively. The half-life (t 1/2) of purified alginate lyase SG4 + at 37 °C was 180 min. Alginate lyase SG4 + in combination with gentamicin and amikacin eradiated 48.4- 52.3% and 58- 64.6%, alginate biofilm formed by P. aeruginosa strains, respectively. The study proves that alginate lyase SG4 + has excellent exopolysaccharide disintegrating ability and may be useful in development of potent therapeutic agent to treat P. aeruginosa biofilms.


Assuntos
Antibacterianos , Biofilmes , Paenibacillus , Polissacarídeo-Liases , Pseudomonas aeruginosa , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/enzimologia , Pseudomonas aeruginosa/genética , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Polissacarídeo-Liases/metabolismo , Polissacarídeo-Liases/genética , Antibacterianos/farmacologia , Paenibacillus/genética , Paenibacillus/enzimologia , Paenibacillus/efeitos dos fármacos , Gentamicinas/farmacologia , Amicacina/farmacologia , Fermentação , Testes de Sensibilidade Microbiana , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Alginatos/metabolismo
17.
Structure ; 32(8): 1137-1149.e4, 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-38815576

RESUMO

Two pore channels are lysosomal cation channels with crucial roles in tumor angiogenesis and viral release from endosomes. Inhibition of the two-pore channel 2 (TPC2) has emerged as potential therapeutic strategy for the treatment of cancers and viral infections, including Ebola and COVID-19. Here, we demonstrate that antagonist SG-094, a synthetic analog of the Chinese alkaloid medicine tetrandrine with increased potency and reduced toxicity, induces asymmetrical structural changes leading to a single binding pocket at only one intersubunit interface within the asymmetrical dimer. Supported by functional characterization of mutants by Ca2+ imaging and patch clamp experiments, we identify key residues in S1 and S4 involved in compound binding to the voltage sensing domain II. SG-094 arrests IIS4 in a downward shifted state which prevents pore opening via the IIS4/S5 linker, hence resembling gating modifiers of canonical VGICs. These findings may guide the rational development of new therapeutics antagonizing TPC2 activity.


Assuntos
Canais de Cálcio , Humanos , Canais de Cálcio/metabolismo , Canais de Cálcio/química , Sítios de Ligação , Lisossomos/metabolismo , Células HEK293 , Ligação Proteica , Cálcio/metabolismo , Bloqueadores dos Canais de Cálcio/farmacologia , Bloqueadores dos Canais de Cálcio/química , Bloqueadores dos Canais de Cálcio/metabolismo , Modelos Moleculares , Canais de Dois Poros
18.
Front Oncol ; 14: 1323366, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38665947

RESUMO

In 2020, bladder cancer, which commonly presents as urothelial carcinoma, became the 10th most common malignancy. For patients with metastatic urothelial carcinoma, the standard first-line treatment remains platinum-based chemotherapy, with immunotherapy serving as an alternative in cases of programmed death ligand 1 expression. However, treatment options become limited upon resistance to platinum and programmed death 1 or programmed death ligand 1 agents. Since the FDA's approval of Enfortumab Vedotin and Sacituzumab Govitecan, the therapeutic landscape has expanded, heralding a shift towards antibody-drug conjugates as potential first-line therapies. Our review employed a robust scientometric approach to assess 475 publications on antibody-drug conjugates in urothelial carcinoma, revealing a surge in related studies since 2018, predominantly led by U.S. institutions. Moreover, 89 clinical trials were examined, with 36 in Phase II and 13 in Phase III, exploring antibody-drug conjugates as both monotherapies and in combination with other agents. Promisingly, novel targets like HER-2 and EpCAM exhibit substantial therapeutic potential. These findings affirm the increasing significance of antibody-drug conjugates in urothelial carcinoma treatment, transitioning them from posterior-line to frontline therapies. Future research is poised to focus on new therapeutic targets, combination therapy optimization, treatment personalization, exploration of double antibody-coupled drugs, and strategies to overcome drug resistance.

19.
J Vet Med Sci ; 86(6): 645-652, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38644182

RESUMO

Bovine herpesvirus 4 (BoHV-4) is an indigenous virus in cattle prevalent mainly in North and South American countries and European countries, but the genomic sequences and genetic characteristics of Japanese strains have not been reported. BoHV-4 is suspected, but not proven, to be associated with various diseases. In the present study, we isolated BoHV-4 from a 10-month-old Japanese Black calf with respiratory symptoms in Japan. To identify the genetic characteristics of the isolate named strain SG20, complete genome sequencing was performed using a combination of next-generation and Sanger sequencing technologies. The complete long unique coding region (LUR) of SG20 was found to comprise 108,819 nucleotides with 41.4% GC content and contain at least 78 open reading frames. It shares 83.4 to 99.3% overall nucleotide identity with six BoHV-4 strains available in the database. The deduced amino acid sequence alignment revealed that SG20 contains genotype 1-specific features of BoHV-4, such as amino acid substitutions and insertions within the glycoprotein B region. Phylogenetic analyzes based on the nucleotide sequences of ORF20 indicated that the virus belonged to genotype 1 (Movar 33/63-like group). The strain was also analyzed using the complete LUR and placed in the same clade as a strain recently isolated from China, but it was distinct from American and European BoHV-4 strains of genotype 1. Although further genomic and epidemiologic information is needed, our results help elucidate the molecular epidemiology of BoHV-4 and provide a foundation for future studies.


Assuntos
Doenças dos Bovinos , Genoma Viral , Infecções por Herpesviridae , Herpesvirus Bovino 4 , Filogenia , Animais , Bovinos , Doenças dos Bovinos/virologia , Doenças dos Bovinos/epidemiologia , Herpesvirus Bovino 4/genética , Herpesvirus Bovino 4/isolamento & purificação , Infecções por Herpesviridae/veterinária , Infecções por Herpesviridae/virologia , Japão/epidemiologia , Sequenciamento Completo do Genoma , Fases de Leitura Aberta , Genótipo
20.
Trends Biochem Sci ; 49(6): 494-505, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38565496

RESUMO

Autophagy - a highly regulated intracellular degradation process - is pivotal in maintaining cellular homeostasis. Liquid-liquid phase separation (LLPS) is a fundamental mechanism regulating the formation and function of membrane-less compartments. Recent research has unveiled connections between LLPS and autophagy, suggesting that phase separation events may orchestrate the spatiotemporal organization of autophagic machinery and cargo sequestration. The Unc-51-like kinase (ULK)/autophagy-related 1 (Atg1) family of proteins is best known for its regulatory role in initiating autophagy, but there is growing evidence that the functional spectrum of ULK/Atg1 extends beyond autophagy regulation. In this review, we explore the spatial and temporal regulation of the ULK/Atg1 family of kinases, focusing on their recruitment to LLPS-driven compartments, and highlighting their multifaceted functions beyond their traditional role.


Assuntos
Proteína Homóloga à Proteína-1 Relacionada à Autofagia , Autofagia , Humanos , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/metabolismo , Animais , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/química
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA